committed step
{{Short description|Irreversible reaction step at the branch points of biochemical pathways}}
In biochemistry, the committed step (also known as the first committed step) is an effectively irreversible, enzyme-catalyzed reaction that occurs at a branch point during the biosynthesis of some molecules.{{cite book |author =Bhagavan, N. V. |title=Medical biochemistry |url =https://archive.org/details/medicalbiochemis0000bhag_a8z8 |url-access =registration |publisher=Harcourt/Academic Press |location=San Diego |year=2002 |isbn=0-12-095440-0 }}{{cite book|last1=Berg|first1=Jeremy M.|last2=Tymoczko|first2=John L.|last3=Stryer|first3=Lubert|title=Biochemistry|url=https://archive.org/details/biochemistry200100jere|url-access=registration|edition=5th|year=2002|publisher=W. H. Freeman and Company|isbn=0-7167-3051-0|page=[https://archive.org/details/biochemistry200100jere/page/447 447]}}
As the name implies, after this step, the molecules are "committed" to the pathway and will ultimately end up in the pathway's final product. The first committed step should not be confused with the rate-limiting step, which is the step with the highest flux control coefficient. It is rare that the first committed step is in fact the rate-determining step.{{cite journal |last1=Sauro |first1=Herbert M. |title=Control and regulation of pathways via negative feedback |journal=Journal of the Royal Society Interface |date=February 2017 |volume=14 |issue=127 |pages=20160848 |doi=10.1098/rsif.2016.0848|pmid=28202588 |pmc=5332569 |doi-access=free }}{{cite journal |last1=Hofmeyr |first1=Jan-Hendrik S. |last2=Cornish-Bowden |first2=Athel |title=Quantitative assessment of regulation in metabolic systems |journal=European Journal of Biochemistry |date=August 1991 |volume=200 |issue=1 |pages=223–236 |doi=10.1111/j.1432-1033.1991.tb21071.x|pmid=1879427 }}
Regulation
Metabolic pathways require tight regulation, so that the proper compounds get produced in the proper amounts at the proper time. Often, the first committed step is regulated by processes such as feedback inhibition and activation. Such regulation ensures that pathway intermediates do not accumulate, a situation that can be wasteful or even harmful to the cell.
Examples of enzymes that catalyze the first committed steps of metabolic pathways
- Phosphofructokinase 1 catalyzes the first committed step of glycolysis.{{cite web|url=http://www.wiley.com/college/pratt/0471393878/student/structure/phosphofructokinase/index.html|title=Phosphofructokinase Regulation|publisher=Wiley Essential Biochemistry|access-date=17 February 2010}}
- LpxC catalyzes the first committed step of lipid A biosynthesis.{{cite journal |vauthors=Raetz C, Whitfield C |title=Lipopolysaccharide endotoxins |journal=Annu Rev Biochem |volume=71 |pages=635–700 |year= 2002|pmid=12045108 |doi=10.1146/annurev.biochem.71.110601.135414 |pmc=2569852}}
- 8-amino-7-oxononanoate synthase catalyzes the first committed step in plant biotin synthesis.{{cite journal |vauthors=Pinon V, Ravanel S, Douce R, Alban C |title=Biotin synthesis in plants. The first committed step of the pathway is catalyzed by a cytosolic 7-keto-8-aminopelargonic acid synthase |journal=Plant Physiology |volume=139 |issue=4 |pages=1666–76 |year=2005 |pmid=16299174 |url=http://www.plantphysiol.org/cgi/content/full/139/4/1666 |doi=10.1104/pp.105.070144 |pmc=1310550}}
- MurA catalyzes the first committed step of peptidoglycan biosynthesis.{{cite journal |vauthors=Brown ED, Vivas EI, Walsh CT, Kolter R |title=MurA (MurZ), the enzyme that catalyzes the first committed step in peptidoglycan biosynthesis, is essential in Escherichia coli |journal=J. Bacteriol. |volume=177 |issue=14 |pages=4194–7 |date=July 1995 |pmid=7608103 |pmc=177162 |doi=10.1128/jb.177.14.4194-4197.1995 }}
- Aspartate transcarbamoylase catalyzes the committed step in the pyrimidine biosynthetic pathway in E. coli.
- 3-deoxy-D-arabinose-heptulsonate 7-phosphate synthase catalyses the first committed step of the shikimate pathway responsible for the synthesis of the aromatic amino acids Tyrosine, Tryptophan and Phenylalanine in plants, bacteria, fungi and some lower eukaryotes.
- Citrate synthase catalyzes the addition of acetyl-CoA to oxaloacetate and is the first committed step of the Citric Acid Cycle.{{Cite book|url=https://www.worldcat.org/oclc/44162497|title=Biochemistry & molecular biology of plants|date=2000|publisher=American Society of Plant Physiologists|others=Bob B. Buchanan, Wilhelm Gruissem, Russell L. Jones|isbn=0-943088-37-2|location=Rockville, Md.|oclc=44162497}}
- Acetyl-CoA carboxylase catalyzes the irreversible carboxylation of acetyl-CoA to malonyl-CoA in the first committed step of fatty acid biosynthesis.
- Glucose-6-phosphate dehydrogenase catalyzes the conversion of G6P into 6-phosphogluconolactone to produce NADPH in the first and committed step of the pentose phosphate pathway.
Other uses
The term has also been applied to other processes that involve a series of steps. For example, the binding of egg and sperm can be thought of as the first committed step in metazoan fertilization.{{cite journal |vauthors=Dell A, Chalabi S, Easton RL |title=Murine and human zona pellucida 3 derived from mouse eggs express identical O-glycans |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=100 |issue=26 |pages=15631–6 |date=December 2003 |pmid=14673092 |pmc=307619 |doi=10.1073/pnas.2635507100 |bibcode=2003PNAS..10015631D |display-authors=etal|doi-access=free }}
See also
References
{{Reflist}}
External links
- [https://web.archive.org/web/20110918042851/http://www.cliffsnotes.com/study_guide/Glycolysis-Regulation.topicArticleId-24998,articleId-24983.html Glycolysis Regulation] at Cliffsnotes.com