Metabolism#Evolution

{{further|Biomolecule|Cell (biology)|Biochemistry}}

File:Trimyristin-3D-vdW.png lipid]]

Most of the structures that make up animals, plants and microbes are made from four basic classes of molecules: amino acids, carbohydrates, nucleic acid and lipids (often called fats). As these molecules are vital for life, metabolic reactions either focus on making these molecules during the construction of cells and tissues, or on breaking them down and using them to obtain energy, by their digestion. These biochemicals can be joined to make polymers such as DNA and proteins, essential macromolecules of life.{{cite journal| vauthors = Cooper GM |date=2000|title=The Molecular Composition of Cells|url=https://www.ncbi.nlm.nih.gov/books/NBK9879/|journal=The Cell: A Molecular Approach | edition = 2nd |language=en|access-date=25 June 2020|archive-date=27 August 2020|archive-url=https://web.archive.org/web/20200827120320/https://www.ncbi.nlm.nih.gov/books/NBK9879/|url-status=live}}

{{Main|Protein}}

Proteins are made of amino acids arranged in a linear chain joined by peptide bonds. Many proteins are enzymes that catalyze the chemical reactions in metabolism. Other proteins have structural or mechanical functions, such as those that form the cytoskeleton, a system of scaffolding that maintains the cell shape.{{cite journal | vauthors = Michie KA, Löwe J | title = Dynamic filaments of the bacterial cytoskeleton | journal = Annual Review of Biochemistry | volume = 75 | pages = 467–92 | year = 2006 | pmid = 16756499 | doi = 10.1146/annurev.biochem.75.103004.142452 | s2cid = 4550126 }} Proteins are also important in cell signaling, immune responses, cell adhesion, active transport across membranes, and the cell cycle.{{cite book | vauthors = Nelson DL, Cox MM | title = Lehninger Principles of Biochemistry | publisher = W. H. Freeman and company | year = 2005 | location = New York | page = [https://archive.org/details/lehningerprincip00lehn_0/page/841 841] | isbn = 978-0-7167-4339-2 | url-access = registration | url = https://archive.org/details/lehningerprincip00lehn_0/page/841 }} Amino acids also contribute to cellular energy metabolism by providing a carbon source for entry into the citric acid cycle (tricarboxylic acid cycle),{{cite journal | vauthors = Kelleher JK, Bryan BM, Mallet RT, Holleran AL, Murphy AN, Fiskum G | title = Analysis of tricarboxylic acid-cycle metabolism of hepatoma cells by comparison of 14CO2 ratios | journal = The Biochemical Journal | volume = 246 | issue = 3 | pages = 633–9 | date = September 1987 | pmid = 3120698 | pmc = 1148327 | doi = 10.1042/bj2460633 }} especially when a primary source of energy, such as glucose, is scarce, or when cells undergo metabolic stress.{{cite journal | vauthors = Hothersall JS, Ahmed A | title = Metabolic fate of the increased yeast amino Acid uptake subsequent to catabolite derepression | journal = Journal of Amino Acids | volume = 2013 | pages = 461901 | year = 2013 | pmid = 23431419 | pmc = 3575661 | doi = 10.1155/2013/461901 | doi-access = free }}

{{Main|Biolipid}}

Lipids are the most diverse group of biochemicals. Their main structural uses are as part of internal and external biological membranes, such as the cell membrane. Their chemical energy can also be used. Lipids contain a long, non-polar hydrocarbon chain with a small polar region containing oxygen. Lipids are usually defined as hydrophobic or amphipathic biological molecules but will dissolve in organic solvents such as ethanol, benzene or chloroform.{{cite journal | vauthors = Fahy E, Subramaniam S, Brown HA, Glass CK, Merrill AH, Murphy RC, Raetz CR, Russell DW, Seyama Y, Shaw W, Shimizu T, Spener F, van Meer G, VanNieuwenhze MS, White SH, Witztum JL, Dennis EA | display-authors = 6 | title = A comprehensive classification system for lipids | journal = Journal of Lipid Research | volume = 46 | issue = 5 | pages = 839–61 | date = May 2005 | pmid = 15722563 | doi = 10.1194/jlr.E400004-JLR200 | doi-access = free }} The fats are a large group of compounds that contain fatty acids and glycerol; a glycerol molecule attached to three fatty acids by ester linkages is called a triacylglyceride.{{cite web|title=Lipid nomenclature Lip-1 & Lip-2|url=https://www.qmul.ac.uk/sbcs/iupac/lipid/lip1n2.html#p11|access-date=2020-06-06|website=qmul.ac.uk|archive-date=6 June 2020|archive-url=https://web.archive.org/web/20200606140055/https://www.qmul.ac.uk/sbcs/iupac/lipid/lip1n2.html#p11|url-status=live}} Several variations of the basic structure exist, including backbones such as sphingosine in sphingomyelin, and hydrophilic groups such as phosphate in phospholipids. Steroids such as sterol are another major class of lipids.{{cite book|edition=8|title=Biochemistry|location=New York|isbn=978-1-4641-2610-9|oclc=913469736 | vauthors = Berg JM, Tymoczko JL, Gatto Jr GJ, Stryer L |date=8 April 2015|publisher=W. H. Freeman|pages=362}}

File:Glucose Fisher to Haworth.gif can exist in both a straight-chain and ring form.]]{{Main|Carbohydrate}}

Carbohydrates are aldehydes or ketones, with many hydroxyl groups attached, that can exist as straight chains or rings. Carbohydrates are the most abundant biological molecules, and fill numerous roles, such as the storage and transport of energy (starch, glycogen) and structural components (cellulose in plants, chitin in animals). The basic carbohydrate units are called monosaccharides and include galactose, fructose, and most importantly glucose. Monosaccharides can be linked together to form polysaccharides in almost limitless ways.{{cite journal | vauthors = Raman R, Raguram S, Venkataraman G, Paulson JC, Sasisekharan R | title = Glycomics: an integrated systems approach to structure-function relationships of glycans | journal = Nature Methods | volume = 2 | issue = 11 | pages = 817–24 | date = November 2005 | pmid = 16278650 | doi = 10.1038/nmeth807 | s2cid = 4644919 }}

{{Main|Nucleotide}}

The two nucleic acids, DNA and RNA, are polymers of nucleotides. Each nucleotide is composed of a phosphate attached to a ribose or deoxyribose sugar group which is attached to a nitrogenous base. Nucleic acids are critical for the storage and use of genetic information, and its interpretation through the processes of transcription and protein biosynthesis. This information is protected by DNA repair mechanisms and propagated through DNA replication. Many viruses have an RNA genome, such as HIV, which uses reverse transcription to create a DNA template from its viral RNA genome.{{cite journal | vauthors = Sierra S, Kupfer B, Kaiser R | title = Basics of the virology of HIV-1 and its replication | journal = Journal of Clinical Virology | volume = 34 | issue = 4 | pages = 233–44 | date = December 2005 | pmid = 16198625 | doi = 10.1016/j.jcv.2005.09.004 }} RNA in ribozymes such as spliceosomes and ribosomes is similar to enzymes as it can catalyze chemical reactions. Individual nucleosides are made by attaching a nucleobase to a ribose sugar. These bases are heterocyclic rings containing nitrogen, classified as purines or pyrimidines. Nucleotides also act as coenzymes in metabolic-group-transfer reactions.{{cite journal | vauthors = Wimmer MJ, Rose IA | title = Mechanisms of enzyme-catalyzed group transfer reactions | journal = Annual Review of Biochemistry | volume = 47 | pages = 1031–78 | year = 1978 | pmid = 354490 | doi = 10.1146/annurev.bi.47.070178.005123 }}

File:Adenosintriphosphat protoniert.svg (ATP), a central intermediate in energy metabolism]]

{{main|Coenzyme}}

Metabolism involves a vast array of chemical reactions, but most fall under a few basic types of reactions that involve the transfer of functional groups of atoms and their bonds within molecules.{{cite journal | vauthors = Mitchell P | title = The Ninth Sir Hans Krebs Lecture. Compartmentation and communication in living systems. Ligand conduction: a general catalytic principle in chemical, osmotic and chemiosmotic reaction systems | journal = European Journal of Biochemistry | volume = 95 | issue = 1 | pages = 1–20 | date = March 1979 | pmid = 378655 | doi = 10.1111/j.1432-1033.1979.tb12934.x | doi-access = free }} This common chemistry allows cells to use a small set of metabolic intermediates to carry chemical groups between different reactions. These group-transfer intermediates are called coenzymes. Each class of group-transfer reactions is carried out by a particular coenzyme, which is the substrate for a set of enzymes that produce it, and a set of enzymes that consume it. These coenzymes are therefore continuously made, consumed and then recycled.{{cite journal | vauthors = Dimroth P, von Ballmoos C, Meier T | title = Catalytic and mechanical cycles in F-ATP synthases. Fourth in the Cycles Review Series | journal = EMBO Reports | volume = 7 | issue = 3 | pages = 276–82 | date = March 2006 | pmid = 16607397 | pmc = 1456893 | doi = 10.1038/sj.embor.7400646 }}

One central coenzyme is adenosine triphosphate (ATP), the energy currency of cells. This nucleotide is used to transfer chemical energy between different chemical reactions. There is only a small amount of ATP in cells, but as it is continuously regenerated, the human body can use about its own weight in ATP per day. ATP acts as a bridge between catabolism and anabolism. Catabolism breaks down molecules, and anabolism puts them together. Catabolic reactions generate ATP, and anabolic reactions consume it. It also serves as a carrier of phosphate groups in phosphorylation reactions.{{cite journal | vauthors = Bonora M, Patergnani S, Rimessi A, De Marchi E, Suski JM, Bononi A, Giorgi C, Marchi S, Missiroli S, Poletti F, Wieckowski MR, Pinton P | display-authors = 6 | title = ATP synthesis and storage | journal = Purinergic Signalling | volume = 8 | issue = 3 | pages = 343–57 | date = September 2012 | pmid = 22528680 | pmc = 3360099 | doi = 10.1007/s11302-012-9305-8 }}

A vitamin is an organic compound needed in small quantities that cannot be made in cells. In human nutrition, most vitamins function as coenzymes after modification; for example, all water-soluble vitamins are phosphorylated or are coupled to nucleotides when they are used in cells.{{cite journal| vauthors = Berg JM, Tymoczko JL, Stryer L |date=2002|title=Vitamins Are Often Precursors to Coenzymes|url=https://www.ncbi.nlm.nih.gov/books/NBK22549/|journal=Biochemistry. 5th Edition|language=en|access-date=9 June 2020|archive-date=15 December 2020|archive-url=https://web.archive.org/web/20201215232601/https://www.ncbi.nlm.nih.gov/books/NBK22549/|url-status=live}} Nicotinamide adenine dinucleotide (NAD⁺), a derivative of vitamin B₃ (niacin), is an important coenzyme that acts as a hydrogen acceptor. Hundreds of separate types of dehydrogenases remove electrons from their substrates and reduce NAD⁺ into NADH. This reduced form of the coenzyme is then a substrate for any of the reductases in the cell that need to transfer hydrogen atoms to their substrates.{{cite journal | vauthors = Pollak N, Dölle C, Ziegler M | title = The power to reduce: pyridine nucleotides--small molecules with a multitude of functions | journal = The Biochemical Journal | volume = 402 | issue = 2 | pages = 205–18 | date = March 2007 | pmid = 17295611 | pmc = 1798440 | doi = 10.1042/BJ20061638 }} Nicotinamide adenine dinucleotide exists in two related forms in the cell, NADH and NADPH. The NAD⁺/NADH form is more important in catabolic reactions, while NADP⁺/NADPH is used in anabolic reactions.{{cite book| vauthors = Fatih Y |title=Advances in food biochemistry|publisher=CRC Press|year=2009|isbn=978-1-4200-0769-5|location=Boca Raton|pages=228|oclc=607553259}}

File:1GZX Haemoglobin.png. The protein subunits are in red and blue, and the iron-containing heme groups in green. From {{PDB|1GZX}}.]]

{{further||Bioinorganic chemistry}}

Inorganic elements play critical roles in metabolism; some are abundant (e.g. sodium and potassium) while others function at minute concentrations. About 99% of a human's body weight is made up of the elements carbon, nitrogen, calcium, sodium, chlorine, potassium, hydrogen, phosphorus, oxygen and sulfur. Organic compounds (proteins, lipids and carbohydrates) contain the majority of the carbon and nitrogen; most of the oxygen and hydrogen is present as water.{{cite journal | vauthors = Heymsfield SB, Waki M, Kehayias J, Lichtman S, Dilmanian FA, Kamen Y, Wang J, Pierson RN | display-authors = 6 | title = Chemical and elemental analysis of humans in vivo using improved body composition models | journal = The American Journal of Physiology | volume = 261 | issue = 2 Pt 1 | pages = E190-8 | date = August 1991 | pmid = 1872381 | doi = 10.1152/ajpendo.1991.261.2.E190 }}

The abundant inorganic elements act as electrolytes. The most important ions are sodium, potassium, calcium, magnesium, chloride, phosphate and the organic ion bicarbonate. The maintenance of precise ion gradients across cell membranes maintains osmotic pressure and pH.{{cite book | chapter = Electrolyte Balance | chapter-url = https://opentextbc.ca/anatomyandphysiology/chapter/26-3-electrolyte-balance/ | title = Anatomy and Physiology | publisher = OpenStax | access-date = 23 June 2020 | archive-date = 2 June 2020 | archive-url = https://web.archive.org/web/20200602222138/https://opentextbc.ca/anatomyandphysiology/chapter/26-3-electrolyte-balance/ | url-status = dead }} Ions are also critical for nerve and muscle function, as action potentials in these tissues are produced by the exchange of electrolytes between the extracellular fluid and the cell's fluid, the cytosol.{{cite book | vauthors = Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J |date=2000 |chapter=The Action Potential and Conduction of Electric Impulses |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK21668/ |title=Molecular Cell Biology |edition=4th |language=en |via=NCBI |access-date=23 June 2020 |archive-date=30 May 2020 |archive-url=https://web.archive.org/web/20200530112637/https://www.ncbi.nlm.nih.gov/books/NBK21668/ |url-status=live }} Electrolytes enter and leave cells through proteins in the cell membrane called ion channels. For example, muscle contraction depends upon the movement of calcium, sodium and potassium through ion channels in the cell membrane and T-tubules.{{cite journal | vauthors = Dulhunty AF | title = Excitation-contraction coupling from the 1950s into the new millennium | journal = Clinical and Experimental Pharmacology & Physiology | volume = 33 | issue = 9 | pages = 763–72 | date = September 2006 | pmid = 16922804 | doi = 10.1111/j.1440-1681.2006.04441.x | s2cid = 37462321 }}

Transition metals are usually present as trace elements in organisms, with zinc and iron being most abundant of those.{{cite book| vauthors = Torres-Romero JC, Alvarez-Sánchez ME, Fernández-Martín K, Alvarez-Sánchez LC, Arana-Argáez V, Ramírez-Camacho M, Lara-Riegos J | chapter=Zinc Efflux in Trichomonas vaginalis: In Silico Identification and Expression Analysis of CDF-Like Genes|date=2018| title =Quantitative Models for Microscopic to Macroscopic Biological Macromolecules and Tissues|pages=149–168| veditors = Olivares-Quiroz L, Resendis-Antonio O |place=Cham|publisher=Springer International Publishing|language=en|doi=10.1007/978-3-319-73975-5_8|isbn=978-3-319-73975-5 }} Metal cofactors are bound tightly to specific sites in proteins; although enzyme cofactors can be modified during catalysis, they always return to their original state by the end of the reaction catalyzed. Metal micronutrients are taken up into organisms by specific transporters and bind to storage proteins such as ferritin or metallothionein when not in use.{{cite journal | vauthors = Cousins RJ, Liuzzi JP, Lichten LA | title = Mammalian zinc transport, trafficking, and signals | journal = The Journal of Biological Chemistry | volume = 281 | issue = 34 | pages = 24085–9 | date = August 2006 | pmid = 16793761 | doi = 10.1074/jbc.R600011200 | doi-access = free }}{{cite journal | vauthors = Dunn LL, Suryo Rahmanto Y, Richardson DR | title = Iron uptake and metabolism in the new millennium | journal = Trends in Cell Biology | volume = 17 | issue = 2 | pages = 93–100 | date = February 2007 | pmid = 17194590 | doi = 10.1016/j.tcb.2006.12.003 }}

{{Main|Catabolism}}

Catabolism is the set of metabolic processes that break down large molecules. These include breaking down and oxidizing food molecules. The purpose of the catabolic reactions is to provide the energy and components needed by anabolic reactions which build molecules.{{cite book| vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P |date=2002|chapter=How Cells Obtain Energy from Food |url= https://www.ncbi.nlm.nih.gov/books/NBK26882/ |title=Molecular Biology of the Cell|edition=4th|language=en|via=NCBI|access-date=25 June 2020|archive-date=5 July 2021|archive-url=https://web.archive.org/web/20210705091156/https://www.ncbi.nlm.nih.gov/books/NBK26882/|url-status=live}} The exact nature of these catabolic reactions differ from organism to organism, and organisms can be classified based on their sources of energy, hydrogen, and carbon (their primary nutritional groups), as shown in the table below. Organic molecules are used as a source of hydrogen atoms or electrons by organotrophs, while lithotrophs use inorganic substrates. Whereas phototrophs convert sunlight to chemical energy,{{cite journal| vauthors = Raven J |date=2009-09-03|title=Contributions of anoxygenic and oxygenic phototrophy and chemolithotrophy to carbon and oxygen fluxes in aquatic environments|url=http://www.int-res.com/abstracts/ame/v56/n2-3/p177-192/|journal=Aquatic Microbial Ecology|language=en|volume=56|pages=177–192|doi=10.3354/ame01315|issn=0948-3055|doi-access=free|access-date=25 June 2020|archive-date=25 June 2020|archive-url=https://web.archive.org/web/20200625091103/http://www.int-res.com/abstracts/ame/v56/n2-3/p177-192/|url-status=live}} chemotrophs depend on redox reactions that involve the transfer of electrons from reduced donor molecules such as organic molecules, hydrogen, hydrogen sulfide or ferrous ions to oxygen, nitrate or sulfate. In animals, these reactions involve complex organic molecules that are broken down to simpler molecules, such as carbon dioxide and water. Photosynthetic organisms, such as plants and cyanobacteria, use similar electron-transfer reactions to store energy absorbed from sunlight.{{cite journal | vauthors = Nelson N, Ben-Shem A | title = The complex architecture of oxygenic photosynthesis | journal = Nature Reviews. Molecular Cell Biology | volume = 5 | issue = 12 | pages = 971–82 | date = December 2004 | pmid = 15573135 | doi = 10.1038/nrm1525 | s2cid = 5686066 }}

The most common set of catabolic reactions in animals can be separated into three main stages. In the first stage, large organic molecules, such as proteins, polysaccharides or lipids, are digested into their smaller components outside cells. Next, these smaller molecules are taken up by cells and converted to smaller molecules, usually acetyl coenzyme A (acetyl-CoA), which releases some energy. Finally, the acetyl group on acetyl-CoA is oxidized to water and carbon dioxide in the citric acid cycle and electron transport chain, releasing more energy while reducing the coenzyme nicotinamide adenine dinucleotide (NAD⁺) into NADH.

{{further|Digestion|Gastrointestinal tract}}

Macromolecules cannot be directly processed by cells. Macromolecules must be broken into smaller units before they can be used in cell metabolism. Different classes of enzymes are used to digest these polymers. These digestive enzymes include proteases that digest proteins into amino acids, as well as glycoside hydrolases that digest polysaccharides into simple sugars known as monosaccharides.{{cite book| vauthors = Demirel Y |title=Energy : production, conversion, storage, conservation, and coupling|publisher=Springer|year=2016|isbn=978-3-319-29650-0|edition=Second|location=Lincoln|pages=431|oclc=945435943}}

Microbes simply secrete digestive enzymes into their surroundings,{{cite journal | vauthors = Häse CC, Finkelstein RA | title = Bacterial extracellular zinc-containing metalloproteases | journal = Microbiological Reviews | volume = 57 | issue = 4 | pages = 823–37 | date = December 1993 | pmid = 8302217 | pmc = 372940 | doi = 10.1128/MMBR.57.4.823-837.1993 }}{{cite journal | vauthors = Gupta R, Gupta N, Rathi P | title = Bacterial lipases: an overview of production, purification and biochemical properties | journal = Applied Microbiology and Biotechnology | volume = 64 | issue = 6 | pages = 763–81 | date = June 2004 | pmid = 14966663 | doi = 10.1007/s00253-004-1568-8 | s2cid = 206934353 }} while animals only secrete these enzymes from specialized cells in their guts, including the stomach and pancreas, and in salivary glands.{{cite journal | vauthors = Hoyle T | title = The digestive system: linking theory and practice | journal = British Journal of Nursing | volume = 6 | issue = 22 | pages = 1285–91 | year = 1997 | pmid = 9470654 | doi = 10.12968/bjon.1997.6.22.1285 }} The amino acids or sugars released by these extracellular enzymes are then pumped into cells by active transport proteins.{{cite journal | vauthors = Souba WW, Pacitti AJ | title = How amino acids get into cells: mechanisms, models, menus, and mediators | journal = Journal of Parenteral and Enteral Nutrition | volume = 16 | issue = 6 | pages = 569–78 | year = 1992 | pmid = 1494216 | doi = 10.1177/0148607192016006569 }}{{cite journal | vauthors = Barrett MP, Walmsley AR, Gould GW | title = Structure and function of facilitative sugar transporters | journal = Current Opinion in Cell Biology | volume = 11 | issue = 4 | pages = 496–502 | date = August 1999 | pmid = 10449337 | doi = 10.1016/S0955-0674(99)80072-6 }}

File:Catabolism schematic.svgs, carbohydrates and fats{{cite journal | last=Sinthupoom | first=Nujarin | last2=Prachayasittikul | first2=Veda | last3=Prachayasittikul | first3=Supaluk | last4=Ruchirawat | first4=Somsak | last5=Prachayasittikul | first5=Virapong | title=Nicotinic acid and derivatives as multifunctional pharmacophores for medical applications | journal=European Food Research and Technology | volume=240 | issue=1 | date=2015 | issn=1438-2377 | doi=10.1007/s00217-014-2354-1 | pages=1–17 | url=http://link.springer.com/10.1007/s00217-014-2354-1 | access-date=2025-04-17}}{{cite journal | last=Clark | first=Audra | last2=Imran | first2=Jonathan | last3=Madni | first3=Tarik | last4=Wolf | first4=Steven E. | title=Nutrition and metabolism in burn patients | journal=Burns & Trauma | volume=5 | date=2017-12-01 | issn=2321-3876 | pmid=28428966 | pmc=5393025 | doi=10.1186/s41038-017-0076-x | doi-access=free | page=}}]]

{{further|Cellular respiration|Fermentation (biochemistry)|Carbohydrate catabolism|Fat catabolism|Protein catabolism}}

Carbohydrate catabolism is the breakdown of carbohydrates into smaller units. Carbohydrates are usually taken into cells after they have been digested into monosaccharides such as glucose and fructose.{{cite journal | vauthors = Bell GI, Burant CF, Takeda J, Gould GW | title = Structure and function of mammalian facilitative sugar transporters | journal = The Journal of Biological Chemistry | volume = 268 | issue = 26 | pages = 19161–4 | date = September 1993 | doi = 10.1016/S0021-9258(19)36489-0 | pmid = 8366068 | doi-access = free }} Once inside, the major route of breakdown is glycolysis, in which glucose is converted into pyruvate. This process generates the energy-conveying molecule NADH from NAD⁺, and generates ATP from ADP for use in powering many processes within the cell.{{cite journal | vauthors = Bouché C, Serdy S, Kahn CR, Goldfine AB | title = The cellular fate of glucose and its relevance in type 2 diabetes | journal = Endocrine Reviews | volume = 25 | issue = 5 | pages = 807–30 | date = October 2004 | pmid = 15466941 | doi = 10.1210/er.2003-0026 | df = dmy-all | doi-access = free }} Pyruvate is an intermediate in several metabolic pathways, but the majority is converted to acetyl-CoA and fed into the citric acid cycle, which enables more ATP production by means of oxidative phosphorylation. This oxidation consumes molecular oxygen and releases water and the waste product carbon dioxide. When oxygen is lacking, or when pyruvate is temporarily produced faster than it can be consumed by the citric acid cycle (as in intense muscular exertion), pyruvate is converted to lactate by the enzyme lactate dehydrogenase, a process that also oxidizes NADH back to NAD⁺ for re-use in further glycolysis, allowing energy production to continue.{{cite journal | vauthors = Alfarouk KO, Verduzco D, Rauch C, Muddathir AK, Adil HH, Elhassan GO, Ibrahim ME, David Polo Orozco J, Cardone RA, Reshkin SJ, Harguindey S | display-authors = 6 | title = Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question | journal = Oncoscience | volume = 1 | issue = 12 | pages = 777–802 | date = 18 December 2014 | pmid = 25621294 | pmc = 4303887 | doi = 10.18632/oncoscience.109 | doi-access = free }} The lactate is later converted back to pyruvate for ATP production where energy is needed, or back to glucose in the Cori cycle. An alternative route for glucose breakdown is the pentose phosphate pathway, which produces less energy but supports anabolism (biomolecule synthesis). This pathway reduces the coenzyme NADP⁺ to NADPH and produces pentose compounds such as ribose 5-phosphate for synthesis of many biomolecules such as nucleotides and aromatic amino acids.{{cite journal |last1=Kruger |first1=Nicholas J |last2=von Schaewen |first2=Antje |title=The oxidative pentose phosphate pathway: structure and organisation |journal=Current Opinion in Plant Biology |volume=6 |date=2003 |issue=3 |doi=10.1016/S1369-5266(03)00039-6 |pages=236–246|pmid=12753973 |bibcode=2003COPB....6..236K }}

File:Carbon Catabolism.png

Fats are catabolized by hydrolysis to free fatty acids and glycerol. The glycerol enters glycolysis and the fatty acids are broken down by beta oxidation to release acetyl-CoA, which then is fed into the citric acid cycle. Fatty acids release more energy upon oxidation than carbohydrates. Steroids are also broken down by some bacteria in a process similar to beta oxidation, and this breakdown process involves the release of significant amounts of acetyl-CoA, propionyl-CoA, and pyruvate, which can all be used by the cell for energy. M. tuberculosis can also grow on the lipid cholesterol as a sole source of carbon, and genes involved in the cholesterol-use pathway(s) have been validated as important during various stages of the infection lifecycle of M. tuberculosis.{{cite journal | vauthors = Wipperman MF, Sampson NS, Thomas ST | title = Pathogen roid rage: cholesterol utilization by Mycobacterium tuberculosis | journal = Critical Reviews in Biochemistry and Molecular Biology | volume = 49 | issue = 4 | pages = 269–93 | date = 2014 | pmid = 24611808 | pmc = 4255906 | doi = 10.3109/10409238.2014.895700 }}

Amino acids are either used to synthesize proteins and other biomolecules, or oxidized to urea and carbon dioxide to produce energy.{{cite journal | vauthors = Sakami W, Harrington H | title = Amino Acid Metabolism | journal = Annual Review of Biochemistry | volume = 32 | pages = 355–98 | year = 1963 | pmid = 14144484 | doi = 10.1146/annurev.bi.32.070163.002035 }} The oxidation pathway starts with the removal of the amino group by a transaminase. The amino group is fed into the urea cycle, leaving a deaminated carbon skeleton in the form of a keto acid. Several of these keto acids are intermediates in the citric acid cycle, for example α-ketoglutarate formed by deamination of glutamate.{{cite journal | vauthors = Brosnan JT | title = Glutamate, at the interface between amino acid and carbohydrate metabolism | journal = The Journal of Nutrition | volume = 130 | issue = 4S Suppl | pages = 988S–90S | date = April 2000 | pmid = 10736367 | doi = 10.1093/jn/130.4.988S | doi-access = free }} The glucogenic amino acids can also be converted into glucose, through gluconeogenesis.{{cite journal | vauthors = Young VR, Ajami AM | title = Glutamine: the emperor or his clothes? | journal = The Journal of Nutrition | volume = 131 | issue = 9 Suppl | pages = 2449S–59S; discussion 2486S–7S | date = September 2001 | pmid = 11533293 | doi = 10.1093/jn/131.9.2449S | doi-access = free }}

{{further|Oxidative phosphorylation|Chemiosmosis|Mitochondrion}}

In oxidative phosphorylation, the electrons removed from organic molecules in areas such as the citric acid cycle are transferred to oxygen and the energy released is used to make ATP. This is done in eukaryotes by a series of proteins in the membranes of mitochondria called the electron transport chain. In prokaryotes, these proteins are found in the cell's inner membrane.{{cite journal | vauthors = Hosler JP, Ferguson-Miller S, Mills DA | title = Energy transduction: proton transfer through the respiratory complexes | journal = Annual Review of Biochemistry | volume = 75 | pages = 165–87 | year = 2006 | pmid = 16756489 | pmc = 2659341 | doi = 10.1146/annurev.biochem.75.062003.101730 }} These proteins use the energy from reduced molecules like NADH to pump protons across a membrane.{{cite journal | vauthors = Schultz BE, Chan SI | title = Structures and proton-pumping strategies of mitochondrial respiratory enzymes | journal = Annual Review of Biophysics and Biomolecular Structure | volume = 30 | pages = 23–65 | year = 2001 | pmid = 11340051 | doi = 10.1146/annurev.biophys.30.1.23 | url = https://authors.library.caltech.edu/1623/1/SCHarbbs01.pdf | access-date = 11 November 2019 | archive-date = 22 January 2020 | archive-url = https://web.archive.org/web/20200122235247/https://authors.library.caltech.edu/1623/1/SCHarbbs01.pdf | url-status = live }}

File:ATPsyn.gif. ATP is shown in red, ADP and phosphate in pink and the rotating stalk subunit in black.]]

Pumping protons out of the mitochondria creates a proton concentration difference across the membrane and generates an electrochemical gradient.{{cite journal | vauthors = Capaldi RA, Aggeler R | title = Mechanism of the F(1)F(0)-type ATP synthase, a biological rotary motor | journal = Trends in Biochemical Sciences | volume = 27 | issue = 3 | pages = 154–60 | date = March 2002 | pmid = 11893513 | doi = 10.1016/S0968-0004(01)02051-5 }} This force drives protons back into the mitochondrion through the base of an enzyme called ATP synthase. The flow of protons makes the stalk subunit rotate, causing the active site of the synthase domain to change shape and phosphorylate adenosine diphosphate—turning it into ATP.

{{further|Microbial metabolism|Nitrogen cycle}}

Chemolithotrophy is a type of metabolism found in prokaryotes where energy is obtained from the oxidation of inorganic compounds. These organisms can use hydrogen,{{cite journal | vauthors = Friedrich B, Schwartz E | title = Molecular biology of hydrogen utilization in aerobic chemolithotrophs | journal = Annual Review of Microbiology | volume = 47 | pages = 351–83 | year = 1993 | pmid = 8257102 | doi = 10.1146/annurev.mi.47.100193.002031 }} reduced sulfur compounds (such as sulfide, hydrogen sulfide and thiosulfate), ferrous iron (Fe(II)){{cite journal | vauthors = Weber KA, Achenbach LA, Coates JD | title = Microorganisms pumping iron: anaerobic microbial iron oxidation and reduction | journal = Nature Reviews. Microbiology | volume = 4 | issue = 10 | pages = 752–64 | date = October 2006 | pmid = 16980937 | doi = 10.1038/nrmicro1490 | url = https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1203&context=bioscifacpub | s2cid = 8528196 | access-date = 6 October 2019 | archive-date = 2 May 2019 | archive-url = https://web.archive.org/web/20190502051428/https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1203&context=bioscifacpub | url-status = live }} or ammonia{{cite journal | vauthors = Jetten MS, Strous M, van de Pas-Schoonen KT, Schalk J, van Dongen UG, van de Graaf AA, Logemann S, Muyzer G, van Loosdrecht MC, Kuenen JG | display-authors = 6 | title = The anaerobic oxidation of ammonium | journal = FEMS Microbiology Reviews | volume = 22 | issue = 5 | pages = 421–37 | date = December 1998 | pmid = 9990725 | doi = 10.1111/j.1574-6976.1998.tb00379.x | doi-access = free }} as sources of reducing power and they gain energy from the oxidation of these compounds.{{cite journal | vauthors = Simon J | title = Enzymology and bioenergetics of respiratory nitrite ammonification | journal = FEMS Microbiology Reviews | volume = 26 | issue = 3 | pages = 285–309 | date = August 2002 | pmid = 12165429 | doi = 10.1111/j.1574-6976.2002.tb00616.x | doi-access = free }} These microbial processes are important in global biogeochemical cycles such as acetogenesis, nitrification and denitrification and are critical for soil fertility.{{cite journal | vauthors = Conrad R | title = Soil microorganisms as controllers of atmospheric trace gases (H2, CO, CH4, OCS, N2O, and NO) | journal = Microbiological Reviews | volume = 60 | issue = 4 | pages = 609–40 | date = December 1996 | pmid = 8987358 | pmc = 239458 | doi = 10.1128/MMBR.60.4.609-640.1996 }}{{cite journal | vauthors = Barea JM, Pozo MJ, Azcón R, Azcón-Aguilar C | title = Microbial co-operation in the rhizosphere | journal = Journal of Experimental Botany | volume = 56 | issue = 417 | pages = 1761–78 | date = July 2005 | pmid = 15911555 | doi = 10.1093/jxb/eri197 | doi-access = free }}

{{further|Phototroph|Photophosphorylation|Chloroplast}}

The energy in sunlight is captured by plants, cyanobacteria, purple bacteria, green sulfur bacteria and some protists. This process is often coupled to the conversion of carbon dioxide into organic compounds, as part of photosynthesis, which is discussed below. The energy capture and carbon fixation systems can, however, operate separately in prokaryotes, as purple bacteria and green sulfur bacteria can use sunlight as a source of energy, while switching between carbon fixation and the fermentation of organic compounds.{{cite journal | vauthors = van der Meer MT, Schouten S, Bateson MM, Nübel U, Wieland A, Kühl M, de Leeuw JW, Sinninghe Damsté JS, Ward DM | display-authors = 6 | title = Diel variations in carbon metabolism by green nonsulfur-like bacteria in alkaline siliceous hot spring microbial mats from Yellowstone National Park | journal = Applied and Environmental Microbiology | volume = 71 | issue = 7 | pages = 3978–86 | date = July 2005 | pmid = 16000812 | pmc = 1168979 | doi = 10.1128/AEM.71.7.3978-3986.2005 | bibcode = 2005ApEnM..71.3978V }}{{cite journal | vauthors = Tichi MA, Tabita FR | title = Interactive control of Rhodobacter capsulatus redox-balancing systems during phototrophic metabolism | journal = Journal of Bacteriology | volume = 183 | issue = 21 | pages = 6344–54 | date = November 2001 | pmid = 11591679 | pmc = 100130 | doi = 10.1128/JB.183.21.6344-6354.2001 }}

In many organisms, the capture of solar energy is similar in principle to oxidative phosphorylation, as it involves the storage of energy as a proton concentration gradient. This proton motive force then drives ATP synthesis.{{cite book | vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P |date=2002|chapter=Energy Conversion: Mitochondria and Chloroplasts|url=https://www.ncbi.nlm.nih.gov/books/NBK21063/|title=Molecular Biology of the Cell | edition = 4th |language=en|access-date=3 July 2020|archive-date=15 December 2020|archive-url=https://web.archive.org/web/20201215131416/https://www.ncbi.nlm.nih.gov/books/NBK21063/|url-status=live}} The electrons needed to drive this electron transport chain come from light-gathering proteins called photosynthetic reaction centres. Reaction centers are classified into two types depending on the nature of photosynthetic pigment present, with most photosynthetic bacteria only having one type, while plants and cyanobacteria have two.{{cite journal | vauthors = Allen JP, Williams JC | title = Photosynthetic reaction centers | journal = FEBS Letters | volume = 438 | issue = 1–2 | pages = 5–9 | date = October 1998 | pmid = 9821949 | doi = 10.1016/S0014-5793(98)01245-9 | bibcode = 1998FEBSL.438....5A | s2cid = 21596537 }}

In plants, algae, and cyanobacteria, photosystem II uses light energy to remove electrons from water, releasing oxygen as a waste product. The electrons then flow to the cytochrome b6f complex, which uses their energy to pump protons across the thylakoid membrane in the chloroplast. These protons move back through the membrane as they drive the ATP synthase, as before. The electrons then flow through photosystem I and can then be used to reduce the coenzyme NADP⁺.^{{{cite journal | vauthors = Munekage Y, Hashimoto M, Miyake C, Tomizawa K, Endo T, Tasaka M, Shikanai T | title = Cyclic electron flow around photosystem I is essential for photosynthesis | journal = Nature | volume = 429 | issue = 6991 | pages = 579–82 | date = June 2004 | pmid = 15175756 | doi = 10.1038/nature02598 | bibcode = 2004Natur.429..579M | s2cid = 4421776 }}} This coenzyme can enter the Calvin cycle or be recycled for further ATP generation.{{Cite journal |last1=Michelet |first1=Laure |last2=Zaffagnini |first2=Mirko |last3=Morisse |first3=Samuel |last4=Sparla |first4=Francesca |last5=Pérez-Pérez |first5=María Esther |last6=Francia |first6=Francesco |last7=Danon |first7=Antoine |last8=Marchand |first8=Christophe |last9=Fermani |first9=Simona |last10=Trost |first10=Paolo |last11=Lemaire |first11=Stéphane D. |date=2013-11-25 |title=Redox regulation of the Calvin–Benson cycle: something old, something new |journal=Frontiers in Plant Science |language=English |volume=4 |page=470 |doi=10.3389/fpls.2013.00470 |doi-access=free |issn=1664-462X |pmc=3838966 |pmid=24324475}}

{{further|Anabolism}}

Anabolism is the set of constructive metabolic processes where the energy released by catabolism is used to synthesize complex molecules. In general, the complex molecules that make up cellular structures are constructed step-by-step from smaller and simpler precursors. Anabolism involves three basic stages. First, the production of precursors such as amino acids, monosaccharides, isoprenoids and nucleotides, secondly, their activation into reactive forms using energy from ATP, and thirdly, the assembly of these precursors into complex molecules such as proteins, polysaccharides, lipids and nucleic acids.{{cite web| vauthors = Mandal A |date=2009-11-26|title=What is Anabolism?|url=https://www.news-medical.net/life-sciences/What-is-Anabolism.aspx|access-date=2020-07-04|website=News-Medical.net|language=en|archive-date=5 July 2020|archive-url=https://web.archive.org/web/20200705173136/https://www.news-medical.net/life-sciences/What-is-Anabolism.aspx|url-status=live}}

Anabolism in organisms can be different according to the source of constructed molecules in their cells. Autotrophs such as plants can construct the complex organic molecules in their cells such as polysaccharides and proteins from simple molecules like carbon dioxide and water. Heterotrophs, on the other hand, require a source of more complex substances, such as monosaccharides and amino acids, to produce these complex molecules. Organisms can be further classified by ultimate source of their energy: photoautotrophs and photoheterotrophs obtain energy from light, whereas chemoautotrophs and chemoheterotrophs obtain energy from oxidation reactions.

{{further|Photosynthesis|Carbon fixation|Chemosynthesis}}

File:Plagiomnium affine laminazellen.jpeg

Photosynthesis is the synthesis of carbohydrates from sunlight and carbon dioxide (CO₂). In plants, cyanobacteria and algae, oxygenic photosynthesis splits water, with oxygen produced as a waste product. This process uses the ATP and NADPH produced by the photosynthetic reaction centres, as described above, to convert CO₂ into glycerate 3-phosphate, which can then be converted into glucose. This carbon-fixation reaction is carried out by the enzyme RuBisCO as part of the Calvin–Benson cycle.{{cite journal | vauthors = Miziorko HM, Lorimer GH | title = Ribulose-1,5-bisphosphate carboxylase-oxygenase | journal = Annual Review of Biochemistry | volume = 52 | pages = 507–35 | year = 1983 | pmid = 6351728 | doi = 10.1146/annurev.bi.52.070183.002451 }} Three types of photosynthesis occur in plants, C3 carbon fixation, C4 carbon fixation and CAM photosynthesis. These differ by the route that carbon dioxide takes to the Calvin cycle, with C3 plants fixing CO₂ directly, while C4 and CAM photosynthesis incorporate the CO₂ into other compounds first, as adaptations to deal with intense sunlight and dry conditions.{{cite journal | vauthors = Dodd AN, Borland AM, Haslam RP, Griffiths H, Maxwell K | title = Crassulacean acid metabolism: plastic, fantastic | journal = Journal of Experimental Botany | volume = 53 | issue = 369 | pages = 569–80 | date = April 2002 | pmid = 11886877 | doi = 10.1093/jexbot/53.369.569 | doi-access = free }}

In photosynthetic prokaryotes the mechanisms of carbon fixation are more diverse. Here, carbon dioxide can be fixed by the Calvin–Benson cycle, a reversed citric acid cycle,{{cite journal | vauthors = Hügler M, Wirsen CO, Fuchs G, Taylor CD, Sievert SM | title = Evidence for autotrophic CO2 fixation via the reductive tricarboxylic acid cycle by members of the epsilon subdivision of proteobacteria | journal = Journal of Bacteriology | volume = 187 | issue = 9 | pages = 3020–7 | date = May 2005 | pmid = 15838028 | pmc = 1082812 | doi = 10.1128/JB.187.9.3020-3027.2005 }} or the carboxylation of acetyl-CoA.{{cite journal | vauthors = Strauss G, Fuchs G | title = Enzymes of a novel autotrophic CO2 fixation pathway in the phototrophic bacterium Chloroflexus aurantiacus, the 3-hydroxypropionate cycle | journal = European Journal of Biochemistry | volume = 215 | issue = 3 | pages = 633–43 | date = August 1993 | pmid = 8354269 | doi = 10.1111/j.1432-1033.1993.tb18074.x | doi-access = free }}{{cite journal | vauthors = Wood HG | title = Life with CO or CO2 and H2 as a source of carbon and energy | journal = FASEB Journal | volume = 5 | issue = 2 | pages = 156–63 | date = February 1991 | pmid = 1900793 | doi = 10.1096/fasebj.5.2.1900793 | doi-access = free | s2cid = 45967404 }} Prokaryotic chemoautotrophs also fix CO₂ through the Calvin–Benson cycle, but use energy from inorganic compounds to drive the reaction.{{cite journal | vauthors = Shively JM, van Keulen G, Meijer WG | title = Something from almost nothing: carbon dioxide fixation in chemoautotrophs | journal = Annual Review of Microbiology | volume = 52 | pages = 191–230 | year = 1998 | pmid = 9891798 | doi = 10.1146/annurev.micro.52.1.191 }}

{{further|Gluconeogenesis|Glyoxylate cycle|Glycogenesis|Glycosylation}}

In carbohydrate anabolism, simple organic acids can be converted into monosaccharides such as glucose and then used to assemble polysaccharides such as starch. The generation of glucose from compounds like pyruvate, lactate, glycerol, glycerate 3-phosphate and amino acids is called gluconeogenesis. Gluconeogenesis converts pyruvate to glucose-6-phosphate through a series of intermediates, many of which are shared with glycolysis. However, this pathway is not simply glycolysis run in reverse, as several steps are catalyzed by non-glycolytic enzymes. This is important as it allows the formation and breakdown of glucose to be regulated separately, and prevents both pathways from running simultaneously in a futile cycle.{{cite journal | vauthors = Boiteux A, Hess B | title = Design of glycolysis | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 293 | issue = 1063 | pages = 5–22 | date = June 1981 | pmid = 6115423 | doi = 10.1098/rstb.1981.0056 | doi-access = free | bibcode = 1981RSPTB.293....5B }}{{cite journal | vauthors = Pilkis SJ, el-Maghrabi MR, Claus TH | title = Fructose-2,6-bisphosphate in control of hepatic gluconeogenesis. From metabolites to molecular genetics | journal = Diabetes Care | volume = 13 | issue = 6 | pages = 582–99 | date = June 1990 | pmid = 2162755 | doi = 10.2337/diacare.13.6.582 | s2cid = 44741368 }}

Although fat is a common way of storing energy, in vertebrates such as humans the fatty acids in these stores cannot be converted to glucose through gluconeogenesis as these organisms cannot convert acetyl-CoA into pyruvate; plants do, but animals do not, have the necessary enzymatic machinery.{{cite journal | vauthors = Ensign SA | title = Revisiting the glyoxylate cycle: alternate pathways for microbial acetate assimilation | journal = Molecular Microbiology | volume = 61 | issue = 2 | pages = 274–6 | date = July 2006 | pmid = 16856935 | doi = 10.1111/j.1365-2958.2006.05247.x | s2cid = 39986630 | doi-access = free }} As a result, after long-term starvation, vertebrates need to produce ketone bodies from fatty acids to replace glucose in tissues such as the brain that cannot metabolize fatty acids.{{cite journal | vauthors = Finn PF, Dice JF | title = Proteolytic and lipolytic responses to starvation | journal = Nutrition | volume = 22 | issue = 7–8 | pages = 830–44 | year = 2006 | pmid = 16815497 | doi = 10.1016/j.nut.2006.04.008 }} In other organisms such as plants and bacteria, this metabolic problem is solved using the glyoxylate cycle, which bypasses the decarboxylation step in the citric acid cycle and allows the transformation of acetyl-CoA to oxaloacetate, where it can be used for the production of glucose.{{cite journal | vauthors = Kornberg HL, Krebs HA | title = Synthesis of cell constituents from C2-units by a modified tricarboxylic acid cycle | journal = Nature | volume = 179 | issue = 4568 | pages = 988–91 | date = May 1957 | pmid = 13430766 | doi = 10.1038/179988a0 | s2cid = 40858130 | bibcode = 1957Natur.179..988K }} Other than fat, glucose is stored in most tissues, as an energy resource available within the tissue through glycogenesis which was usually being used to maintained glucose level in blood.{{cite journal| vauthors = Evans RD, Heather LC |date=June 2016|title=Metabolic pathways and abnormalities|journal=Surgery (Oxford)|volume=34|issue=6|pages=266–272|doi=10.1016/j.mpsur.2016.03.010|s2cid=87884121 |issn=0263-9319|url=https://ora.ox.ac.uk/objects/uuid:84c0a8e7-38e9-4de2-ba19-9f129a07987a|access-date=28 August 2020|archive-date=31 October 2020|archive-url=https://web.archive.org/web/20201031143458/https://ora.ox.ac.uk/objects/uuid:84c0a8e7-38e9-4de2-ba19-9f129a07987a|url-status=live}}

Polysaccharides and glycans are made by the sequential addition of monosaccharides by glycosyltransferase from a reactive sugar-phosphate donor such as uridine diphosphate glucose (UDP-Glc) to an acceptor hydroxyl group on the growing polysaccharide. As any of the hydroxyl groups on the ring of the substrate can be acceptors, the polysaccharides produced can have straight or branched structures.{{cite book | vauthors = Freeze HH, Hart GW, Schnaar RL | chapter=Glycosylation Precursors |date=2015 |url=http://www.ncbi.nlm.nih.gov/books/NBK453043/ |title=Essentials of Glycobiology| veditors = Varki A, Cummings RD, Esko JD, Stanley P |edition=3rd |place=Cold Spring Harbor (NY) |publisher=Cold Spring Harbor Laboratory Press |pmid=28876856 |access-date=2020-07-08 |doi=10.1101/glycobiology.3e.005|doi-broken-date=1 November 2024 |archive-date=24 February 2022|archive-url=https://web.archive.org/web/20220224114901/https://www.ncbi.nlm.nih.gov/books/NBK453043/|url-status=live}} The polysaccharides produced can have structural or metabolic functions themselves, or be transferred to lipids and proteins by the enzymes oligosaccharyltransferases.{{cite journal | vauthors = Opdenakker G, Rudd PM, Ponting CP, Dwek RA | title = Concepts and principles of glycobiology | journal = FASEB Journal | volume = 7 | issue = 14 | pages = 1330–7 | date = November 1993 | pmid = 8224606 | doi = 10.1096/fasebj.7.14.8224606 | doi-access = free | s2cid = 10388991 }}{{cite journal | vauthors = McConville MJ, Menon AK | title = Recent developments in the cell biology and biochemistry of glycosylphosphatidylinositol lipids (review) | journal = Molecular Membrane Biology | volume = 17 | issue = 1 | pages = 1–16 | year = 2000 | pmid = 10824734 | doi = 10.1080/096876800294443 | doi-access = free }}

{{further|Fatty acid synthesis|Steroid metabolism}}

File:Sterol synthesis.svg pathway with the intermediates isopentenyl pyrophosphate (IPP), dimethylallyl pyrophosphate (DMAPP), geranyl pyrophosphate (GPP) and squalene shown. Some intermediates are omitted for clarity.]]

Fatty acids are made by fatty acid synthases that polymerize and then reduce acetyl-CoA units. The acyl chains in the fatty acids are extended by a cycle of reactions that add the acyl group, reduce it to an alcohol, dehydrate it to an alkene group and then reduce it again to an alkane group. The enzymes of fatty acid biosynthesis are divided into two groups: in animals and fungi, all these fatty acid synthase reactions are carried out by a single multifunctional type I protein,{{cite journal | vauthors = Chirala SS, Wakil SJ | title = Structure and function of animal fatty acid synthase | journal = Lipids | volume = 39 | issue = 11 | pages = 1045–53 | date = November 2004 | pmid = 15726818 | doi = 10.1007/s11745-004-1329-9 | s2cid = 4043407 }} while in plant plastids and bacteria separate type II enzymes perform each step in the pathway.{{cite journal | vauthors = White SW, Zheng J, Zhang YM | title = The structural biology of type II fatty acid biosynthesis | journal = Annual Review of Biochemistry | volume = 74 | pages = 791–831 | year = 2005 | pmid = 15952903 | doi = 10.1146/annurev.biochem.74.082803.133524 }}{{cite journal | vauthors = Ohlrogge JB, Jaworski JG | title = Regulation of Fatty Acid Synthesis | journal = Annual Review of Plant Physiology and Plant Molecular Biology | volume = 48 | pages = 109–136 | date = June 1997 | pmid = 15012259 | doi = 10.1146/annurev.arplant.48.1.109 | s2cid = 46348092 }}

Terpenes and isoprenoids are a large class of lipids that include the carotenoids and form the largest class of plant natural products.{{cite journal | vauthors = Dubey VS, Bhalla R, Luthra R | title = An overview of the non-mevalonate pathway for terpenoid biosynthesis in plants | journal = Journal of Biosciences | volume = 28 | issue = 5 | pages = 637–46 | date = September 2003 | pmid = 14517367 | doi = 10.1007/BF02703339 | url = http://www.ias.ac.in/jbiosci/sep2003/637.pdf | url-status = dead | s2cid = 27523830 | archive-url = https://web.archive.org/web/20070415213325/http://www.ias.ac.in/jbiosci/sep2003/637.pdf | archive-date = 15 April 2007 }} These compounds are made by the assembly and modification of isoprene units donated from the reactive precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate.{{cite journal | vauthors = Kuzuyama T, Seto H | title = Diversity of the biosynthesis of the isoprene units | journal = Natural Product Reports | volume = 20 | issue = 2 | pages = 171–83 | date = April 2003 | pmid = 12735695 | doi = 10.1039/b109860h }} These precursors can be made in different ways. In animals and archaea, the mevalonate pathway produces these compounds from acetyl-CoA,{{cite journal | vauthors = Grochowski LL, Xu H, White RH | title = Methanocaldococcus jannaschii uses a modified mevalonate pathway for biosynthesis of isopentenyl diphosphate | journal = Journal of Bacteriology | volume = 188 | issue = 9 | pages = 3192–8 | date = May 2006 | pmid = 16621811 | pmc = 1447442 | doi = 10.1128/JB.188.9.3192-3198.2006 }} while in plants and bacteria the non-mevalonate pathway uses pyruvate and glyceraldehyde 3-phosphate as substrates.{{cite journal | vauthors = Lichtenthaler HK | title = The 1-Deoxy-D-Xylulose-5-Phosphate Pathway of Isoprenoid Biosynthesis in Plants | journal = Annual Review of Plant Physiology and Plant Molecular Biology | volume = 50 | pages = 47–65 | date = June 1999 | pmid = 15012203 | doi = 10.1146/annurev.arplant.50.1.47 }} One important reaction that uses these activated isoprene donors is sterol biosynthesis. Here, the isoprene units are joined to make squalene and then folded up and formed into a set of rings to make lanosterol.{{cite journal | vauthors = Schroepfer GJ | title = Sterol biosynthesis | journal = Annual Review of Biochemistry | volume = 50 | pages = 585–621 | year = 1981 | pmid = 7023367 | doi = 10.1146/annurev.bi.50.070181.003101 }} Lanosterol can then be converted into other sterols such as cholesterol and ergosterol.{{cite journal | vauthors = Lees ND, Skaggs B, Kirsch DR, Bard M | title = Cloning of the late genes in the ergosterol biosynthetic pathway of Saccharomyces cerevisiae--a review | journal = Lipids | volume = 30 | issue = 3 | pages = 221–6 | date = March 1995 | pmid = 7791529 | doi = 10.1007/BF02537824 | s2cid = 4019443 }}

{{further|Protein biosynthesis|Amino acid synthesis}}

Organisms vary in their ability to synthesize the 20 common amino acids. Most bacteria and plants can synthesize all twenty, but mammals can only synthesize eleven nonessential amino acids, so nine essential amino acids must be obtained from food. Some simple parasites, such as the bacteria Mycoplasma pneumoniae, lack all amino acid synthesis and take their amino acids directly from their hosts.{{cite journal | vauthors = Himmelreich R, Hilbert H, Plagens H, Pirkl E, Li BC, Herrmann R | title = Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae | journal = Nucleic Acids Research | volume = 24 | issue = 22 | pages = 4420–49 | date = November 1996 | pmid = 8948633 | pmc = 146264 | doi = 10.1093/nar/24.22.4420 }} All amino acids are synthesized from intermediates in glycolysis, the citric acid cycle, or the pentose phosphate pathway. Nitrogen is provided by glutamate and glutamine. Nonessensial amino acid synthesis depends on the formation of the appropriate alpha-keto acid, which is then transaminated to form an amino acid.{{cite book | vauthors = Guyton AC, Hall JE |title=Textbook of Medical Physiology |url=https://archive.org/details/textbookmedicalp00acgu |url-access=limited |publisher=Elsevier |year=2006 |location=Philadelphia |pages=[https://archive.org/details/textbookmedicalp00acgu/page/n889 855]–6 |isbn=978-0-7216-0240-0}}

Amino acids are made into proteins by being joined in a chain of peptide bonds. Each different protein has a unique sequence of amino acid residues: this is its primary structure. Just as the letters of the alphabet can be combined to form an almost endless variety of words, amino acids can be linked in varying sequences to form a huge variety of proteins. Proteins are made from amino acids that have been activated by attachment to a transfer RNA molecule through an ester bond. This aminoacyl-tRNA precursor is produced in an ATP-dependent reaction carried out by an aminoacyl tRNA synthetase.{{cite journal | vauthors = Ibba M, Söll D | title = The renaissance of aminoacyl-tRNA synthesis | journal = EMBO Reports | volume = 2 | issue = 5 | pages = 382–7 | date = May 2001 | pmid = 11375928 | pmc = 1083889 | doi = 10.1093/embo-reports/kve095 | url = http://www.molcells.org/home/journal/include/downloadPdf.asp?articleuid={A158E3B4-2423-4806-9A30-4B93CDA76DA0} | url-status = dead | archive-url = https://web.archive.org/web/20110501181419/http://www.molcells.org/home/journal/include/downloadPdf.asp?articleuid=%7BA158E3B4-2423-4806-9A30-4B93CDA76DA0%7D | archive-date = 1 May 2011 }} This aminoacyl-tRNA is then a substrate for the ribosome, which joins the amino acid onto the elongating protein chain, using the sequence information in a messenger RNA.{{cite journal | vauthors = Lengyel P, Söll D | title = Mechanism of protein biosynthesis | journal = Bacteriological Reviews | volume = 33 | issue = 2 | pages = 264–301 | date = June 1969 | pmid = 4896351 | pmc = 378322 | doi = 10.1128/MMBR.33.2.264-301.1969 }}

{{further|Nucleotide salvage|Pyrimidine biosynthesis|Purine#Metabolism}}

Nucleotides are made from amino acids, carbon dioxide and formic acid in pathways that require large amounts of metabolic energy.{{cite journal | vauthors = Rudolph FB | title = The biochemistry and physiology of nucleotides | journal = The Journal of Nutrition | volume = 124 | issue = 1 Suppl | pages = 124S–127S | date = January 1994 | pmid = 8283301 | doi = 10.1093/jn/124.suppl_1.124S | doi-access = free }} {{cite journal | vauthors = Zrenner R, Stitt M, Sonnewald U, Boldt R | title = Pyrimidine and purine biosynthesis and degradation in plants | journal = Annual Review of Plant Biology | volume = 57 | pages = 805–36 | year = 2006 | issue = 1 | pmid = 16669783 | doi = 10.1146/annurev.arplant.57.032905.105421 | bibcode = 2006AnRPB..57..805Z }} Consequently, most organisms have efficient systems to salvage preformed nucleotides.{{cite journal | vauthors = Stasolla C, Katahira R, Thorpe TA, Ashihara H | title = Purine and pyrimidine nucleotide metabolism in higher plants | journal = Journal of Plant Physiology | volume = 160 | issue = 11 | pages = 1271–95 | date = November 2003 | pmid = 14658380 | doi = 10.1078/0176-1617-01169 | bibcode = 2003JPPhy.160.1271S }} Purines are synthesized as nucleosides (bases attached to ribose).{{cite journal | vauthors = Davies O, Mendes P, Smallbone K, Malys N | title = Characterisation of multiple substrate-specific (d)ITP/(d)XTPase and modelling of deaminated purine nucleotide metabolism | journal = BMB Reports | volume = 45 | issue = 4 | pages = 259–64 | date = April 2012 | pmid = 22531138 | doi = 10.5483/BMBRep.2012.45.4.259 | url = http://wrap.warwick.ac.uk/49510/1/WRAP_Malys_%5B45-4%5D1204261917_%28259-264%29BMB_11-169.pdf | doi-access = free | access-date = 18 September 2019 | archive-date = 24 October 2020 | archive-url = https://web.archive.org/web/20201024132423/http://wrap.warwick.ac.uk/49510/1/WRAP_Malys_%5B45-4%5D1204261917_%28259-264%29BMB_11-169.pdf | url-status = live }} Both adenine and guanine are made from the precursor nucleoside inosine monophosphate, which is synthesized using atoms from the amino acids glycine, glutamine, and aspartic acid, as well as formate transferred from the coenzyme tetrahydrofolate. Pyrimidines, on the other hand, are synthesized from the base orotate, which is formed from glutamine and aspartate.{{cite journal | vauthors = Smith JL | title = Enzymes of nucleotide synthesis | journal = Current Opinion in Structural Biology | volume = 5 | issue = 6 | pages = 752–7 | date = December 1995 | pmid = 8749362 | doi = 10.1016/0959-440X(95)80007-7 }}

{{further|Xenobiotic metabolism|Drug metabolism|Alcohol metabolism|Antioxidant}}

All organisms are constantly exposed to compounds that they cannot use as foods and that would be harmful if they accumulated in cells, as they have no metabolic function. These potentially damaging compounds are called xenobiotics.{{cite journal | vauthors = Testa B, Krämer SD | title = The biochemistry of drug metabolism--an introduction: part 1. Principles and overview | journal = Chemistry & Biodiversity | volume = 3 | issue = 10 | pages = 1053–101 | date = October 2006 | pmid = 17193224 | doi = 10.1002/cbdv.200690111 | s2cid = 28872968 }} Xenobiotics such as synthetic drugs, natural poisons and antibiotics are detoxified by a set of xenobiotic-metabolizing enzymes. In humans, these include cytochrome P450 oxidases,{{cite journal | vauthors = Danielson PB | title = The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans | journal = Current Drug Metabolism | volume = 3 | issue = 6 | pages = 561–97 | date = December 2002 | pmid = 12369887 | doi = 10.2174/1389200023337054 }} UDP-glucuronosyltransferases,{{cite journal | vauthors = King CD, Rios GR, Green MD, Tephly TR | title = UDP-glucuronosyltransferases | journal = Current Drug Metabolism | volume = 1 | issue = 2 | pages = 143–61 | date = September 2000 | pmid = 11465080 | doi = 10.2174/1389200003339171 }} and glutathione S-transferases.{{cite journal | vauthors = Sheehan D, Meade G, Foley VM, Dowd CA | title = Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily | journal = The Biochemical Journal | volume = 360 | issue = Pt 1 | pages = 1–16 | date = November 2001 | pmid = 11695986 | pmc = 1222196 | doi = 10.1042/0264-6021:3600001 }} This system of enzymes acts in three stages to firstly oxidize the xenobiotic (phase I) and then conjugate water-soluble groups onto the molecule (phase II). The modified water-soluble xenobiotic can then be pumped out of cells and in multicellular organisms may be further metabolized before being excreted (phase III). In ecology, these reactions are particularly important in microbial biodegradation of pollutants and the bioremediation of contaminated land and oil spills.{{cite journal | vauthors = Galvão TC, Mohn WW, de Lorenzo V | title = Exploring the microbial biodegradation and biotransformation gene pool | journal = Trends in Biotechnology | volume = 23 | issue = 10 | pages = 497–506 | date = October 2005 | pmid = 16125262 | doi = 10.1016/j.tibtech.2005.08.002 }} Many of these microbial reactions are shared with multicellular organisms, but due to the incredible diversity of types of microbes these organisms are able to deal with a far wider range of xenobiotics than multicellular organisms, and can degrade even persistent organic pollutants such as organochloride compounds.{{cite journal | vauthors = Janssen DB, Dinkla IJ, Poelarends GJ, Terpstra P | title = Bacterial degradation of xenobiotic compounds: evolution and distribution of novel enzyme activities | journal = Environmental Microbiology | volume = 7 | issue = 12 | pages = 1868–82 | date = December 2005 | pmid = 16309386 | doi = 10.1111/j.1462-2920.2005.00966.x | url = https://pure.rug.nl/ws/files/3623678/2005EnvironMicrobiolJanssen.pdf | doi-access = free | bibcode = 2005EnvMi...7.1868J | access-date = 11 November 2019 | archive-date = 11 November 2019 | archive-url = https://web.archive.org/web/20191111195543/https://pure.rug.nl/ws/files/3623678/2005EnvironMicrobiolJanssen.pdf | url-status = live }}

A related problem for aerobic organisms is oxidative stress.{{cite journal | vauthors = Davies KJ | title = Oxidative stress: the paradox of aerobic life | journal = Biochemical Society Symposium | volume = 61 | pages = 1–31 | year = 1995 | pmid = 8660387 | doi = 10.1042/bss0610001 }} Here, processes including oxidative phosphorylation and the formation of disulfide bonds during protein folding produce reactive oxygen species such as hydrogen peroxide.{{cite journal | vauthors = Tu BP, Weissman JS | title = Oxidative protein folding in eukaryotes: mechanisms and consequences | journal = The Journal of Cell Biology | volume = 164 | issue = 3 | pages = 341–6 | date = February 2004 | pmid = 14757749 | pmc = 2172237 | doi = 10.1083/jcb.200311055 }} These damaging oxidants are removed by antioxidant metabolites such as glutathione and enzymes such as catalases and peroxidases.{{cite journal | vauthors = Sies H | title = Oxidative stress: oxidants and antioxidants | journal = Experimental Physiology | volume = 82 | issue = 2 | pages = 291–5 | date = March 1997 | pmid = 9129943 | doi = 10.1113/expphysiol.1997.sp004024 | s2cid = 20240552 | doi-access = free }}{{cite journal | vauthors = Vertuani S, Angusti A, Manfredini S | title = The antioxidants and pro-antioxidants network: an overview | journal = Current Pharmaceutical Design | volume = 10 | issue = 14 | pages = 1677–94 | year = 2004 | pmid = 15134565 | doi = 10.2174/1381612043384655 | s2cid = 43713549 }}

{{further|Biological thermodynamics}}

Living organisms must obey the laws of thermodynamics, which describe the transfer of heat and work. The second law of thermodynamics states that in any isolated system, the amount of entropy (disorder) cannot decrease. Although living organisms' amazing complexity appears to contradict this law, life is possible as all organisms are open systems that exchange matter and energy with their surroundings. Living systems are not in equilibrium, but instead are dissipative systems that maintain their state of high complexity by causing a larger increase in the entropy of their environments.{{cite journal | vauthors = von Stockar U, Liu J | title = Does microbial life always feed on negative entropy? Thermodynamic analysis of microbial growth | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1412 | issue = 3 | pages = 191–211 | date = August 1999 | pmid = 10482783 | doi = 10.1016/S0005-2728(99)00065-1 | doi-access = free }} The metabolism of a cell achieves this by coupling the spontaneous processes of catabolism to the non-spontaneous processes of anabolism. In thermodynamic terms, metabolism maintains order by creating disorder.{{cite journal | vauthors = Demirel Y, Sandler SI | title = Thermodynamics and bioenergetics | journal = Biophysical Chemistry | volume = 97 | issue = 2–3 | pages = 87–111 | date = June 2002 | pmid = 12050002 | doi = 10.1016/S0301-4622(02)00069-8 | s2cid = 3754065 | url = https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1006&context=chemengthermalmech | access-date = 22 September 2019 | archive-date = 4 August 2020 | archive-url = https://web.archive.org/web/20200804002615/https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1006&context=chemengthermalmech | url-status = live }}

{{further|Metabolic pathway|Metabolic control analysis|Hormone|Regulatory enzymes|Cell signaling}}

As the environments of most organisms are constantly changing, the reactions of metabolism must be finely regulated to maintain a constant set of conditions within cells, a condition called homeostasis.{{cite journal | vauthors = Albert R | title = Scale-free networks in cell biology | journal = Journal of Cell Science | volume = 118 | issue = Pt 21 | pages = 4947–57 | date = November 2005 | pmid = 16254242 | doi = 10.1242/jcs.02714 | arxiv = q-bio/0510054 | s2cid = 3001195 | bibcode = 2005q.bio....10054A }}{{cite journal | vauthors = Brand MD | title = Regulation analysis of energy metabolism | journal = The Journal of Experimental Biology | volume = 200 | issue = Pt 2 | pages = 193–202 | date = January 1997 | doi = 10.1242/jeb.200.2.193 | pmid = 9050227 | bibcode = 1997JExpB.200..193B | url = http://jeb.biologists.org/cgi/reprint/200/2/193 | access-date = 12 March 2007 | archive-date = 29 March 2007 | archive-url = https://web.archive.org/web/20070329202116/http://jeb.biologists.org/cgi/reprint/200/2/193 | url-status = live }} Metabolic regulation also allows organisms to respond to signals and interact actively with their environments.{{cite journal | vauthors = Soyer OS, Salathé M, Bonhoeffer S | title = Signal transduction networks: topology, response and biochemical processes | journal = Journal of Theoretical Biology | volume = 238 | issue = 2 | pages = 416–25 | date = January 2006 | pmid = 16045939 | doi = 10.1016/j.jtbi.2005.05.030 | bibcode = 2006JThBi.238..416S }} Two closely linked concepts are important for understanding how metabolic pathways are controlled. Firstly, the regulation of an enzyme in a pathway is how its activity is increased and decreased in response to signals. Secondly, the control exerted by this enzyme is the effect that these changes in its activity have on the overall rate of the pathway (the flux through the pathway).{{cite journal | vauthors = Salter M, Knowles RG, Pogson CI | title = Metabolic control | journal = Essays in Biochemistry | volume = 28 | pages = 1–12 | year = 1994 | pmid = 7925313 }} For example, an enzyme may show large changes in activity (i.e. it is highly regulated) but if these changes have little effect on the flux of a metabolic pathway, then this enzyme is not involved in the control of the pathway.{{cite journal | vauthors = Westerhoff HV, Groen AK, Wanders RJ | title = Modern theories of metabolic control and their applications (review) | journal = Bioscience Reports | volume = 4 | issue = 1 | pages = 1–22 | date = January 1984 | pmid = 6365197 | doi = 10.1007/BF01120819 | s2cid = 27791605 }}

File:Insulin glucose metabolism ZP.svg and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6).{{cite book | last=Chouhan | first=Raje | last2=Goswami | first2=Shilpi | last3=Bajpai | first3=Anil Kumar | title=Nanostructures for Oral Medicine | chapter=Recent advancements in oral delivery of insulin: from challenges to solutions | publisher=Elsevier | date=2017 | isbn=978-0-323-47720-8 | doi=10.1016/b978-0-323-47720-8.00016-x | url=https://linkinghub.elsevier.com/retrieve/pii/B978032347720800016X | access-date=2025-04-17 | page=435–465}}]]

There are multiple levels of metabolic regulation. In intrinsic regulation, the metabolic pathway self-regulates to respond to changes in the levels of substrates or products; for example, a decrease in the amount of product can increase the flux through the pathway to compensate. This type of regulation often involves allosteric regulation of the activities of multiple enzymes in the pathway.{{cite journal | vauthors = Fell DA, Thomas S | title = Physiological control of metabolic flux: the requirement for multisite modulation | journal = The Biochemical Journal | volume = 311 | issue = Pt 1 | pages = 35–9 | date = October 1995 | pmid = 7575476 | pmc = 1136115 | doi = 10.1042/bj3110035 }} Extrinsic control involves a cell in a multicellular organism changing its metabolism in response to signals from other cells. These signals are usually in the form of water-soluble messengers such as hormones and growth factors and are detected by specific receptors on the cell surface.{{cite journal | vauthors = Hendrickson WA | title = Transduction of biochemical signals across cell membranes | journal = Quarterly Reviews of Biophysics | volume = 38 | issue = 4 | pages = 321–30 | date = November 2005 | pmid = 16600054 | doi = 10.1017/S0033583506004136 | s2cid = 39154236 }} These signals are then transmitted inside the cell by second messenger systems that often involved the phosphorylation of proteins.{{cite journal | vauthors = Cohen P | title = The regulation of protein function by multisite phosphorylation--a 25 year update | journal = Trends in Biochemical Sciences | volume = 25 | issue = 12 | pages = 596–601 | date = December 2000 | pmid = 11116185 | doi = 10.1016/S0968-0004(00)01712-6 }}

A very well understood example of extrinsic control is the regulation of glucose metabolism by the hormone insulin.{{cite journal | vauthors = Lienhard GE, Slot JW, James DE, Mueckler MM | title = How cells absorb glucose | journal = Scientific American | volume = 266 | issue = 1 | pages = 86–91 | date = January 1992 | pmid = 1734513 | doi = 10.1038/scientificamerican0192-86 | bibcode = 1992SciAm.266a..86L }} Insulin is produced in response to rises in blood glucose levels. Binding of the hormone to insulin receptors on cells then activates a cascade of protein kinases that cause the cells to take up glucose and convert it into storage molecules such as fatty acids and glycogen.{{cite journal | vauthors = Roach PJ | title = Glycogen and its metabolism | journal = Current Molecular Medicine | volume = 2 | issue = 2 | pages = 101–20 | date = March 2002 | pmid = 11949930 | doi = 10.2174/1566524024605761 }} The metabolism of glycogen is controlled by activity of phosphorylase, the enzyme that breaks down glycogen, and glycogen synthase, the enzyme that makes it. These enzymes are regulated in a reciprocal fashion, with phosphorylation inhibiting glycogen synthase, but activating phosphorylase. Insulin causes glycogen synthesis by activating protein phosphatases and producing a decrease in the phosphorylation of these enzymes.{{cite journal | vauthors = Newgard CB, Brady MJ, O'Doherty RM, Saltiel AR | title = Organizing glucose disposal: emerging roles of the glycogen targeting subunits of protein phosphatase-1 | journal = Diabetes | volume = 49 | issue = 12 | pages = 1967–77 | date = December 2000 | pmid = 11117996 | doi = 10.2337/diabetes.49.12.1967 | url = http://diabetes.diabetesjournals.org/cgi/reprint/49/12/1967.pdf | doi-access = free | access-date = 25 March 2007 | archive-date = 19 June 2007 | archive-url = https://web.archive.org/web/20070619211503/http://diabetes.diabetesjournals.org/cgi/reprint/49/12/1967.pdf | url-status = live }}

{{further|Proto-metabolism|Molecular evolution|Phylogenetics}}

File:Tree of life int.svg showing the common ancestry of organisms from all three domains of life. Bacteria are colored blue, eukaryotes red, and archaea green. Relative positions of some of the phyla included are shown around the tree.]]

The central pathways of metabolism described above, such as glycolysis and the citric acid cycle, are present in all three domains of living things and were present in the last universal common ancestor.{{cite journal | vauthors = Romano AH, Conway T | title = Evolution of carbohydrate metabolic pathways | journal = Research in Microbiology | volume = 147 | issue = 6–7 | pages = 448–55 | year = 1996 | pmid = 9084754 | doi = 10.1016/0923-2508(96)83998-2 | doi-access = free }} This universal ancestral cell was prokaryotic and probably a methanogen that had extensive amino acid, nucleotide, carbohydrate and lipid metabolism.{{cite book |author=Koch A |title=How Did Bacteria Come to Be? |journal=Adv Microb Physiol |volume=40 |pages=353–99 |year=1998 |pmid=9889982 |doi=10.1016/S0065-2911(08)60135-6 |series=Advances in Microbial Physiology |isbn=978-0-12-027740-7}}{{cite journal | vauthors = Ouzounis C, Kyrpides N | title = The emergence of major cellular processes in evolution | journal = FEBS Letters | volume = 390 | issue = 2 | pages = 119–23 | date = July 1996 | pmid = 8706840 | doi = 10.1016/0014-5793(96)00631-X | s2cid = 39128865 | doi-access = free | bibcode = 1996FEBSL.390..119O }} The retention of these ancient pathways during later evolution may be the result of these reactions having been an optimal solution to their particular metabolic problems, with pathways such as glycolysis and the citric acid cycle producing their end products highly efficiently and in a minimal number of steps. The first pathways of enzyme-based metabolism may have been parts of purine nucleotide metabolism, while previous metabolic pathways were a part of the ancient RNA world.{{cite journal | vauthors = Caetano-Anollés G, Kim HS, Mittenthal JE | title = The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 22 | pages = 9358–63 | date = May 2007 | pmid = 17517598 | pmc = 1890499 | doi = 10.1073/pnas.0701214104 | bibcode = 2007PNAS..104.9358C | doi-access = free }}

Many models have been proposed to describe the mechanisms by which novel metabolic pathways evolve. These include the sequential addition of novel enzymes to a short ancestral pathway, the duplication and then divergence of entire pathways as well as the recruitment of pre-existing enzymes and their assembly into a novel reaction pathway.{{cite journal | vauthors = Schmidt S, Sunyaev S, Bork P, Dandekar T | title = Metabolites: a helping hand for pathway evolution? | journal = Trends in Biochemical Sciences | volume = 28 | issue = 6 | pages = 336–41 | date = June 2003 | pmid = 12826406 | doi = 10.1016/S0968-0004(03)00114-2 }} The relative importance of these mechanisms is unclear, but genomic studies have shown that enzymes in a pathway are likely to have a shared ancestry, suggesting that many pathways have evolved in a step-by-step fashion with novel functions created from pre-existing steps in the pathway.{{cite journal | vauthors = Light S, Kraulis P | title = Network analysis of metabolic enzyme evolution in Escherichia coli | journal = BMC Bioinformatics | volume = 5 | pages = 15 | date = February 2004 | pmid = 15113413 | pmc = 394313 | doi = 10.1186/1471-2105-5-15 | doi-access = free }} {{cite journal | vauthors = Alves R, Chaleil RA, Sternberg MJ | title = Evolution of enzymes in metabolism: a network perspective | journal = Journal of Molecular Biology | volume = 320 | issue = 4 | pages = 751–70 | date = July 2002 | pmid = 12095253 | doi = 10.1016/S0022-2836(02)00546-6 }} An alternative model comes from studies that trace the evolution of proteins' structures in metabolic networks, this has suggested that enzymes are pervasively recruited, borrowing enzymes to perform similar functions in different metabolic pathways (evident in the MANET database){{cite journal | vauthors = Kim HS, Mittenthal JE, Caetano-Anollés G | title = MANET: tracing evolution of protein architecture in metabolic networks | journal = BMC Bioinformatics | volume = 7 | pages = 351 | date = July 2006 | pmid = 16854231 | pmc = 1559654 | doi = 10.1186/1471-2105-7-351 | doi-access = free }} These recruitment processes result in an evolutionary enzymatic mosaic.{{cite journal | vauthors = Teichmann SA, Rison SC, Thornton JM, Riley M, Gough J, Chothia C | title = Small-molecule metabolism: an enzyme mosaic | journal = Trends in Biotechnology | volume = 19 | issue = 12 | pages = 482–6 | date = December 2001 | pmid = 11711174 | doi = 10.1016/S0167-7799(01)01813-3 }} A third possibility is that some parts of metabolism might exist as "modules" that can be reused in different pathways and perform similar functions on different molecules.{{cite journal | vauthors = Spirin V, Gelfand MS, Mironov AA, Mirny LA | title = A metabolic network in the evolutionary context: multiscale structure and modularity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 23 | pages = 8774–9 | date = June 2006 | pmid = 16731630 | pmc = 1482654 | doi = 10.1073/pnas.0510258103 | bibcode = 2006PNAS..103.8774S | doi-access = free }}

As well as the evolution of new metabolic pathways, evolution can also cause the loss of metabolic functions. For example, in some parasites metabolic processes that are not essential for survival are lost and preformed amino acids, nucleotides and carbohydrates may instead be scavenged from the host.{{cite journal | vauthors = Lawrence JG | title = Common themes in the genome strategies of pathogens | journal = Current Opinion in Genetics & Development | volume = 15 | issue = 6 | pages = 584–8 | date = December 2005 | pmid = 16188434 | doi = 10.1016/j.gde.2005.09.007 }} {{cite journal | vauthors = Wernegreen JJ | title = For better or worse: genomic consequences of intracellular mutualism and parasitism | journal = Current Opinion in Genetics & Development | volume = 15 | issue = 6 | pages = 572–83 | date = December 2005 | pmid = 16230003 | doi = 10.1016/j.gde.2005.09.013 }} Similar reduced metabolic capabilities are seen in endosymbiotic organisms.{{cite journal | vauthors = Pál C, Papp B, Lercher MJ, Csermely P, Oliver SG, Hurst LD | title = Chance and necessity in the evolution of minimal metabolic networks | journal = Nature | volume = 440 | issue = 7084 | pages = 667–70 | date = March 2006 | pmid = 16572170 | doi = 10.1038/nature04568 | s2cid = 4424895 | bibcode = 2006Natur.440..667P }}

{{further|Protein methods|Proteomics|Metabolomics|Metabolic network modelling}}

File:A thaliana metabolic network.png of the Arabidopsis thaliana citric acid cycle. Enzymes and metabolites are shown as red squares and the interactions between them as black lines.]]

Classically, metabolism is studied by a reductionist approach that focuses on a single metabolic pathway. Particularly valuable is the use of radioactive tracers at the whole-organism, tissue and cellular levels, which define the paths from precursors to final products by identifying radioactively labelled intermediates and products.{{cite journal | vauthors = Rennie MJ | title = An introduction to the use of tracers in nutrition and metabolism | journal = The Proceedings of the Nutrition Society | volume = 58 | issue = 4 | pages = 935–44 | date = November 1999 | pmid = 10817161 | doi = 10.1017/S002966519900124X | doi-access = free }} The enzymes that catalyze these chemical reactions can then be purified and their kinetics and responses to inhibitors investigated. A parallel approach is to identify the small molecules in a cell or tissue; the complete set of these molecules is called the metabolome. Overall, these studies give a good view of the structure and function of simple metabolic pathways, but are inadequate when applied to more complex systems such as the metabolism of a complete cell.{{cite journal | vauthors = Phair RD | title = Development of kinetic models in the nonlinear world of molecular cell biology | journal = Metabolism | volume = 46 | issue = 12 | pages = 1489–95 | date = December 1997 | pmid = 9439549 | doi = 10.1016/S0026-0495(97)90154-2 | doi-access = free }}

An idea of the complexity of the metabolic networks in cells that contain thousands of different enzymes is given by the figure showing the interactions between just 43 proteins and 40 metabolites to the right: the sequences of genomes provide lists containing anything up to 26.500 genes.{{cite journal | vauthors = Sterck L, Rombauts S, Vandepoele K, Rouzé P, Van de Peer Y | title = How many genes are there in plants (... and why are they there)? | journal = Current Opinion in Plant Biology | volume = 10 | issue = 2 | pages = 199–203 | date = April 2007 | pmid = 17289424 | doi = 10.1016/j.pbi.2007.01.004 }} However, it is now possible to use this genomic data to reconstruct complete networks of biochemical reactions and produce more holistic mathematical models that may explain and predict their behavior.{{cite journal | vauthors = Borodina I, Nielsen J | title = From genomes to in silico cells via metabolic networks | journal = Current Opinion in Biotechnology | volume = 16 | issue = 3 | pages = 350–5 | date = June 2005 | pmid = 15961036 | doi = 10.1016/j.copbio.2005.04.008 }} These models are especially powerful when used to integrate the pathway and metabolite data obtained through classical methods with data on gene expression from proteomic and DNA microarray studies.{{cite journal | vauthors = Gianchandani EP, Brautigan DL, Papin JA | title = Systems analyses characterize integrated functions of biochemical networks | journal = Trends in Biochemical Sciences | volume = 31 | issue = 5 | pages = 284–91 | date = May 2006 | pmid = 16616498 | doi = 10.1016/j.tibs.2006.03.007 }} Using these techniques, a model of human metabolism has now been produced, which will guide future drug discovery and biochemical research.{{cite journal | vauthors = Duarte NC, Becker SA, Jamshidi N, Thiele I, Mo ML, Vo TD, Srivas R, Palsson BØ | display-authors = 6 | title = Global reconstruction of the human metabolic network based on genomic and bibliomic data | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 6 | pages = 1777–82 | date = February 2007 | pmid = 17267599 | pmc = 1794290 | doi = 10.1073/pnas.0610772104 | bibcode = 2007PNAS..104.1777D | doi-access = free }} These models are now used in network analysis, to classify human diseases into groups that share common proteins or metabolites.{{cite journal | vauthors = Goh KI, Cusick ME, Valle D, Childs B, Vidal M, Barabási AL | title = The human disease network | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 21 | pages = 8685–90 | date = May 2007 | pmid = 17502601 | pmc = 1885563 | doi = 10.1073/pnas.0701361104 | bibcode = 2007PNAS..104.8685G | doi-access = free }}{{cite journal | vauthors = Lee DS, Park J, Kay KA, Christakis NA, Oltvai ZN, Barabási AL | title = The implications of human metabolic network topology for disease comorbidity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 29 | pages = 9880–5 | date = July 2008 | pmid = 18599447 | pmc = 2481357 | doi = 10.1073/pnas.0802208105 | bibcode = 2008PNAS..105.9880L | doi-access = free }}

Bacterial metabolic networks are a striking example of bow-tie{{cite journal | vauthors = Csete M, Doyle J | title = Bow ties, metabolism and disease | journal = Trends in Biotechnology | volume = 22 | issue = 9 | pages = 446–50 | date = September 2004 | pmid = 15331224 | doi = 10.1016/j.tibtech.2004.07.007 }}{{cite journal | vauthors = Ma HW, Zeng AP | title = The connectivity structure, giant strong component and centrality of metabolic networks | journal = Bioinformatics | volume = 19 | issue = 11 | pages = 1423–30 | date = July 2003 | pmid = 12874056 | doi = 10.1093/bioinformatics/btg177 | citeseerx = 10.1.1.605.8964 }}{{cite journal | vauthors = Zhao J, Yu H, Luo JH, Cao ZW, Li YX | title = Hierarchical modularity of nested bow-ties in metabolic networks | journal = BMC Bioinformatics | volume = 7 | pages = 386 | date = August 2006 | pmid = 16916470 | pmc = 1560398 | doi = 10.1186/1471-2105-7-386 | arxiv = q-bio/0605003 | bibcode = 2006q.bio.....5003Z | doi-access = free }} organization, an architecture able to input a wide range of nutrients and produce a large variety of products and complex macromolecules using a relatively few intermediate common currencies.{{Cite web |title=Macromolecules: Nutrients, Metabolism, and Digestive Processes {{!}} Virtual High School - KeepNotes |url=https://keepnotes.com/virtual-high-school/sbi3u/1294-macromolecules-nutrients-metabolism-and-digestive-processes |access-date=2023-12-29 |website=keepnotes.com |archive-date=29 December 2023 |archive-url=https://web.archive.org/web/20231229164242/https://keepnotes.com/virtual-high-school/sbi3u/1294-macromolecules-nutrients-metabolism-and-digestive-processes |url-status=dead }}

A major technological application of this information is metabolic engineering. Here, organisms such as yeast, plants or bacteria are genetically modified to make them more useful in biotechnology and aid the production of drugs such as antibiotics or industrial chemicals such as 1,3-propanediol and shikimic acid.{{cite journal | vauthors = Thykaer J, Nielsen J | title = Metabolic engineering of beta-lactam production | journal = Metabolic Engineering | volume = 5 | issue = 1 | pages = 56–69 | date = January 2003 | pmid = 12749845 | doi = 10.1016/S1096-7176(03)00003-X }}{{cite journal | vauthors = González-Pajuelo M, Meynial-Salles I, Mendes F, Andrade JC, Vasconcelos I, Soucaille P | title = Metabolic engineering of Clostridium acetobutylicum for the industrial production of 1,3-propanediol from glycerol | journal = Metabolic Engineering | volume = 7 | issue = 5–6 | pages = 329–36 | year = 2005 | pmid = 16095939 | doi = 10.1016/j.ymben.2005.06.001 | hdl-access = free | hdl = 10400.14/3388 }}{{cite journal | vauthors = Krämer M, Bongaerts J, Bovenberg R, Kremer S, Müller U, Orf S, Wubbolts M, Raeven L | display-authors = 6 | title = Metabolic engineering for microbial production of shikimic acid | journal = Metabolic Engineering | volume = 5 | issue = 4 | pages = 277–83 | date = October 2003 | pmid = 14642355 | doi = 10.1016/j.ymben.2003.09.001 }} These genetic modifications usually aim to reduce the amount of energy used to produce the product, increase yields and reduce the production of wastes.{{cite journal | vauthors = Koffas M, Roberge C, Lee K, Stephanopoulos G | title = Metabolic engineering | journal = Annual Review of Biomedical Engineering | volume = 1 | pages = 535–57 | year = 1999 | pmid = 11701499 | doi = 10.1146/annurev.bioeng.1.1.535 | s2cid = 11814282 }}

{{further|History of biochemistry|History of molecular biology}}

The term metabolism is derived from the Ancient Greek word μεταβολή—"metabole" for "a change" which is derived from μεταβάλλειν—"metaballein", meaning "to change"{{Cite web|title=metabolism {{!}} Origin and meaning of metabolism by Online Etymology Dictionary|url=https://www.etymonline.com/word/metabolism|access-date=2020-07-23|website=www.etymonline.com|language=en|archive-date=21 September 2017|archive-url=https://web.archive.org/web/20170921001422/http://www.etymonline.com/index.php?term=metabolism|url-status=live}}

File:Aristotle's metabolism.png as an open flow model]]

Aristotle's The Parts of Animals sets out enough details of his views on metabolism for an open flow model to be made. He believed that at each stage of the process, materials from food were transformed, with heat being released as the classical element of fire, and residual materials being excreted as urine, bile, or faeces.{{cite book|author=Leroi, Armand Marie|url=https://archive.org/stream/lagoonhowaristot0000lero?ref=ol#page/402/mode/2up|title=The Lagoon: How Aristotle Invented Science|date=2014|publisher=Bloomsbury|isbn=978-1-4088-3622-4|pages=400–401|author-link=Armand Marie Leroi}}

Ibn al-Nafis described metabolism in his 1260 AD work titled Al-Risalah al-Kamiliyyah fil Siera al-Nabawiyyah (The Treatise of Kamil on the Prophet's Biography) which included the following phrase "Both the body and its parts are in a continuous state of dissolution and nourishment, so they are inevitably undergoing permanent change."{{cite conference | vauthors = Al-Roubi AS | date = 1982 | title = Ibn Al-Nafis as a philosopher | conference = Symposium on Ibn al-Nafis, Second International Conference on Islamic Medicine | publisher = Islamic Medical Organization | location = Kuwait }}

The history of the scientific study of metabolism spans several centuries and has moved from examining whole animals in early studies, to examining individual metabolic reactions in modern biochemistry. The first controlled experiments in human metabolism were published by Santorio Santorio in 1614 in his book Ars de statica medicina. He described how he weighed himself before and after eating, sleep, working, sex, fasting, drinking, and excreting. He found that most of the food he took in was lost through what he called "insensible perspiration".{{cite journal | vauthors = Eknoyan G | title = Santorio Sanctorius (1561-1636) - founding father of metabolic balance studies | journal = American Journal of Nephrology | volume = 19 | issue = 2 | pages = 226–33 | year = 1999 | pmid = 10213823 | doi = 10.1159/000013455 | s2cid = 32900603 }}

File:SantoriosMeal.jpg in his steelyard balance, from Ars de statica medicina, first published 1614]]

In these early studies, the mechanisms of these metabolic processes had not been identified and a vital force was thought to animate living tissue.{{cite book|url=https://archive.org/details/historyofscience04willuoft/page/n7/mode/2up|title=Modern Development of the Chemical and Biological Sciences|vauthors=Williams HA|date=1904|publisher=Harper and Brothers|series=A History of Science: in Five Volumes|volume=IV|location=New York|pages=184–185|access-date=26 March 2007}} In the 19th century, when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur concluded that fermentation was catalyzed by substances within the yeast cells he called "ferments". He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells."{{cite journal | vauthors = Manchester KL | title = Louis Pasteur (1822-1895)--chance and the prepared mind | journal = Trends in Biotechnology | volume = 13 | issue = 12 | pages = 511–5 | date = December 1995 | pmid = 8595136 | doi = 10.1016/S0167-7799(00)89014-9 }} This discovery, along with the publication by Friedrich Wöhler in 1828 of a paper on the chemical synthesis of urea, and is notable for being the first organic compound prepared from wholly inorganic precursors.{{cite journal | vauthors = Kinne-Saffran E, Kinne RK | title = Vitalism and synthesis of urea. From Friedrich Wöhler to Hans A. Krebs | journal = American Journal of Nephrology | volume = 19 | issue = 2 | pages = 290–4 | year = 1999 | pmid = 10213830 | doi = 10.1159/000013463 | s2cid = 71727190 }} Wöhler's urea synthesis showed that organic compounds could be created from inorganic precursors, disputing the vital force theory that dominated early 19th-century science. Modern analyses consider this achievement as foundational for unifying organic and inorganic chemistry.{{Cite journal |last=Kinne-Saffran |first=E. |last2=Kinne |first2=R. K. |date=1999 |title=Vitalism and synthesis of urea. From Friedrich Wöhler to Hans A. Krebs |url=https://pubmed.ncbi.nlm.nih.gov/10213830 |journal=American Journal of Nephrology |volume=19 |issue=2 |pages=290–294 |doi=10.1159/000013463 |issn=0250-8095 |pmid=10213830}}

It was the discovery of enzymes at the beginning of the 20th century by Eduard Buchner that separated the study of the chemical reactions of metabolism from the biological study of cells, and marked the beginnings of biochemistry.Eduard Buchner's 1907 [http://nobelprize.org/nobel_prizes/chemistry/laureates/1907/buchner-lecture.html Nobel lecture] {{Webarchive|url=https://web.archive.org/web/20170708144420/http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1907/buchner-lecture.html |date=8 July 2017 }} at http://nobelprize.org {{Webarchive|url=https://web.archive.org/web/20060405023917/http://nobelprize.org/ |date=5 April 2006 }} Accessed 20 March 2007 The mass of biochemical knowledge grew rapidly throughout the early 20th century. One of the most prolific of these modern biochemists was Hans Krebs who made huge contributions to the study of metabolism.{{cite journal | vauthors = Kornberg H | title = Krebs and his trinity of cycles | journal = Nature Reviews. Molecular Cell Biology | volume = 1 | issue = 3 | pages = 225–8 | date = December 2000 | pmid = 11252898 | doi = 10.1038/35043073 | s2cid = 28092593 }} He discovered the urea cycle and later, working with Hans Kornberg, the citric acid cycle and the glyoxylate cycle.{{cite journal |vauthors=Krebs HA, Henseleit K |title=Untersuchungen über die Harnstoffbildung im tierkorper |journal=Z. Physiol. Chem. |volume=210 |issue=1–2 |pages=33–66 |year=1932 |doi=10.1515/bchm2.1932.210.1-2.33}}{{cite journal | vauthors = Krebs HA, Johnson WA | title = Metabolism of ketonic acids in animal tissues | journal = The Biochemical Journal | volume = 31 | issue = 4 | pages = 645–60 | date = April 1937 | pmid = 16746382 | pmc = 1266984 | doi = 10.1042/bj0310645 }} Modern biochemical research has been greatly aided by the development of new techniques such as chromatography, NMR spectroscopy, electron microscopy and molecular dynamics simulations. These techniques have allowed the discovery and detailed analysis of the many molecules and metabolic pathways in cells.{{cite book | last=Das | first=Bidisha | last2=Chakraborty | first2=Joy | last3=Chattopadhyay | first3=Krishnananda | title=Biochemical and Biophysical Methods in Molecular and Cellular Biology | chapter=Emerging Techniques in Cellular and Biomolecular Research | publisher=Springer Nature Singapore | publication-place=Singapore | date=2025 | isbn=978-981--962087-6 | doi=10.1007/978-981-96-2088-3_1 | url=https://link.springer.com/10.1007/978-981-96-2088-3_1 | access-date=2025-04-17 | page=1–28}}

• {{annotated link|Anthropogenic metabolism}}
• {{annotated link|Antimetabolite}}
• {{annotated link|Calorimetry}}
• {{annotated link|Isothermal microcalorimetry}}
• {{annotated link|Inborn errors of metabolism}}
• {{annotated link|Iron–sulfur world hypothesis}}, a "metabolism first" theory of the origin of life
• {{annotated link|Metabolic disorder}}
• Microphysiometry
• {{annotated link|Primary nutritional groups}}
• {{Annotated link|Proto-metabolism}}
• {{annotated link|Respirometry}}
• {{annotated link|Stream metabolism}}
• {{annotated link|Sulfur metabolism}}
• {{annotated link|Specific dynamic action|Thermic effect of food}}
• {{annotated link|Urban metabolism}}
• {{annotated link|Fluid balance|Water metabolism}}
• {{annotated link|Overflow metabolism}}
• Oncometabolism
• {{annotated link|Reactome}}
• {{annotated link|KEGG}}

{{reflist}}

{{Library resources box

|onlinebooks=yes

|by=no

|lcheading=Metabolism

|label=Metabolism

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Introductory

{{refbegin}}

• {{cite book | vauthors = Rose S, Mileusnic R | title = The Chemistry of Life. | publisher = Penguin Press Science | date = 1999 | isbn = 0-14-027273-9 }}
• {{cite book | vauthors = Schneider EC, Sagan D | title = Into the Cool: Energy Flow, Thermodynamics, and Life. | publisher = University of Chicago Press | date = 2005 | isbn = 0-226-73936-8}}
• {{cite book | vauthors = Lane N | title = Oxygen: The Molecule that Made the World. | publisher = Oxford University Press | location= USA | date = 2004 | isbn = 0-19-860783-0 }}

{{refend}}

Advanced

{{refbegin}}

• {{cite book | vauthors = Price N, Stevens L | title = Fundamentals of Enzymology: Cell and Molecular Biology of Catalytic Proteins. | publisher = Oxford University Press | date = 1999 | isbn = 0-19-850229-X }}
• {{cite book | vauthors = Berg J, Tymoczko J, Stryer L | title = Biochemistry | publisher = W. H. Freeman and Company | date = 2002 | isbn = 0-7167-4955-6 }}
• {{cite book | vauthors = Cox M, Nelson DL | title = Lehninger Principles of Biochemistry. | publisher = Palgrave Macmillan | date = 2004 | isbn = 0-7167-4339-6 }}
• {{cite book | author-link1 = Thomas D. Brock | vauthors = Brock TD, Madigan MR, Martinko J, Parker J | title = Brock's Biology of Microorganisms. | publisher = Benjamin Cummings | date = 2002 | isbn = 0-13-066271-2 }}
• {{cite book | vauthors = Da Silva JJ, Williams RJ | title = The Biological Chemistry of the Elements: The Inorganic Chemistry of Life. | publisher = Clarendon Press | date = 1991 | isbn = 0-19-855598-9 }}
• {{cite book | vauthors = Nicholls DG, Ferguson SJ | title = Bioenergetics | publisher = Academic Press Inc. | date = 2002 | isbn = 0-12-518121-3 }}
• {{cite journal | vauthors = Wood HG | title = Life with CO or CO2 and H2 as a source of carbon and energy | journal = FASEB Journal | volume = 5 | issue = 2 | pages = 156–63 | date = February 1991 | pmid = 1900793 | doi = 10.1096/fasebj.5.2.1900793 | doi-access = free | s2cid = 45967404 }}

{{refend}}

{{Wikiversity|Topic:Biochemistry}}

{{wikibooks}}

{{Wiktionary}}

{{Commons category}}

General information

• [https://web.archive.org/web/20050308172226/http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/MB1index.html The Biochemistry of Metabolism] (archived 8 March 2005)
• [http://www.sparknotes.com/testprep/books/sat2/biology/ Sparknotes SAT biochemistry] Overview of biochemistry. School level.
• [http://www.sciencegateway.org/resources/biologytext/index.html MIT Biology Hypertextbook] {{Webarchive|url=http://arquivo.pt/wayback/20160519111914/http://www.sciencegateway.org/resources/biologytext/index.html |date=19 May 2016 }} Undergraduate-level guide to molecular biology.

Human metabolism

• [http://library.med.utah.edu/NetBiochem/titles.htm Topics in Medical Biochemistry] Guide to human metabolic pathways. School level.
• [http://themedicalbiochemistrypage.org/ THE Medical Biochemistry Page] Comprehensive resource on human metabolism.

Databases

• [http://www.expasy.org/cgi-bin/show_thumbnails.pl Flow Chart of Metabolic Pathways] at ExPASy
• [http://www.iubmb-nicholson.org/pdf/MetabolicPathways_6_17_04_.pdf IUBMB-Nicholson Metabolic Pathways Chart]
• [http://bioinformatics.charite.de/supercyp/ SuperCYP: Database for Drug-Cytochrome-Metabolism] {{Webarchive|url=https://web.archive.org/web/20111103123642/http://bioinformatics.charite.de/supercyp/ |date=3 November 2011 }}

Metabolic pathways

• [http://www.genome.ad.jp/kegg/pathway/map/map01100.html Metabolism reference Pathway] {{Webarchive|url=https://web.archive.org/web/20090223112439/http://www.genome.ad.jp/kegg/pathway/map/map01100.html |date=23 February 2009 }}
• {{webarchive |url=https://web.archive.org/web/*/helios.bto.ed.ac.uk/bto/microbes/nitrogen.htm |date=* |title=The Nitrogen cycle and Nitrogen fixation }}

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