palmitoyl-CoA
{{Chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 386554704
| ImageFile = Palmitoyl coenzyme A.svg
| ImageSize = 300px
| IUPACName = 3′-O-Phosphonoadenosine 5′-
| SystematicName = O1-
| OtherNames =
| Section1 = {{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 1763-10-6
| PubChem = 644109
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = C00154
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 559149
| SMILES = CCCCCCCCCCCCCCCC(=O)SCCNC(=O)CCNC(=O)[C@@H](C(C)(C)COP(=O)(O)OP(=O)(O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)n2cnc3c2ncnc3N)O)OP(=O)(O)O)O
| InChI = 1/C37H66N7O17P3S/c1-4-5-6-7-8-9-10-11-12-13-14-15-16-17-28(46)65-21-20-39-27(45)18-19-40-35(49)32(48)37(2,3)23-58-64(55,56)61-63(53,54)57-22-26-31(60-62(50,51)52)30(47)36(59-26)44-25-43-29-33(38)41-24-42-34(29)44/h24-26,30-32,36,47-48H,4-23H2,1-3H3,(H,39,45)(H,40,49)(H,53,54)(H,55,56)(H2,38,41,42)(H2,50,51,52)/t26-,30-,31-,32+,36-/m1/s1
| InChIKey = MNBKLUUYKPBKDU-BBECNAHFBL
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C37H66N7O17P3S/c1-4-5-6-7-8-9-10-11-12-13-14-15-16-17-28(46)65-21-20-39-27(45)18-19-40-35(49)32(48)37(2,3)23-58-64(55,56)61-63(53,54)57-22-26-31(60-62(50,51)52)30(47)36(59-26)44-25-43-29-33(38)41-24-42-34(29)44/h24-26,30-32,36,47-48H,4-23H2,1-3H3,(H,39,45)(H,40,49)(H,53,54)(H,55,56)(H2,38,41,42)(H2,50,51,52)/t26-,30-,31-,32+,36-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = MNBKLUUYKPBKDU-BBECNAHFSA-N
| MeSHName = Palmitoyl+Coenzyme+A
}}
| Section2 = {{Chembox Properties
| C=37 | H=66 | N=7 | O=17 | P=3 | S=1
| Appearance =
| Density =
| MeltingPt =
| BoilingPt =
}}
| Section3 = {{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
}}
}}
Palmitoyl-CoA is an acyl-CoA thioester. It is an "activated" form of palmitic acid and can be transported into the mitochondrial matrix by the carnitine shuttle system (which transports fatty acyl-CoA molecules into the mitochondria), and once inside can participate in beta-oxidation. Alternatively, palmitoyl-CoA is used as a substrate in the biosynthesis of sphingosine (this biosynthetic pathway does not require transfer into the mitochondria).{{cite journal|author1=Brady, R.N.|author2=DiMari, S.J.|author3=Snell, E.E.|year=1969|title=Biosynthesis of sphingolipid bases. 3. Isolation and characterization of ketonic intermediates in the synthesis of sphingosine and dihydrosphingosine by cell-free extracts of Hansenula ciferri|journal=J. Biol. Chem.|volume=244|issue=2|pages=491–496|doi=10.1016/S0021-9258(18)94455-8 |doi-access=free |pmid=4388074}}{{cite journal|author1=Stoffel, W.|author2=Le Kim, D.|author3=Sticht, G.|year=1968|title=Biosynthesis of dihydrosphingosine in vitro|journal=Hoppe-Seyler's Z. Physiol. Chem.|volume=349|issue=5|pages=664–670|doi=10.1515/bchm2.1968.349.1.664|pmid=4386961}}
Biosynthesis
Palmitoyl CoA formed from palmitic acid, in the reaction below.{{Cite book|last1=Voet|first1=Donald|url=https://books.google.com/books?id=9T7hCgAAQBAJ&q=Fatty%20Acids%20Are%20Activated%20by%20Their%20Attachment%20to%20Coenzyme%20A%20voet%20fundamentals%20of%20biochemistry&pg=PA672|title=Fundamentals of Biochemistry: Life at the Molecular Level|last2=Voet|first2=Judith G.|last3=Pratt|first3=Charlotte W.|date=2016-02-29|publisher=John Wiley & Sons|isbn=978-1-118-91840-1|language=en}}
:{{Chem2 | Palmitate + CoA\-SH + ATP -> Palmitoyl\-CoA + AMP + Pyrophosphate }}
This reaction is often referred to as the "activation" of a fatty acid. The activation is catalyzed by palmitoyl-coenzyme A synthetase and the reaction proceeds through a two step mechanism, in which palmitoyl-AMP is an intermediate.{{Cite journal|last1=Bar–Tana|first1=J.|last2=Rose|first2=G.|last3=Brandes|first3=R.|last4=Shapiro|first4=B.|date=1973-02-01|title=Palmitoyl-coenzyme A synthetase. Mechanism of reaction|journal=Biochemical Journal|volume=131|issue=2|pages=199–209|doi=10.1042/bj1310199|pmid=4722436|issn=0264-6021|pmc=1177459}} The reaction is driven to completion by the exergonic hydrolysis of pyrophosphate.
The activation of fatty acids occurs in the cytosol and beta-oxidation occurs in the mitochondria. However, long chain fatty acyl-CoA cannot cross the mitochondrial membrane. If palmitoyl-CoA is to enter the mitochondria, it must react with carnitine in order to be transported across:
:{{Chem2 | Palmitoyl\-CoA + Carnitine <-> Palmitoyl\-Carnitine + CoA\-SH }}
This transesterification reaction is catalyzed by carnitine palmitoyl transferase.{{Citation|last=Sharma|first=R.|chapter=Biochemical Mechanisms of Fatty Liver and Bioactive Foods|date=2013|title=Bioactive Food as Dietary Interventions for Liver and Gastrointestinal Disease|pages=709–741|publisher=Elsevier|doi=10.1016/b978-0-12-397154-8.00041-5|isbn=978-0-12-397154-8}} Palmitoyl-Carnitine may translocate across the membrane, and once on matrix side, the reaction proceeds in reverse as CoA-SH is recombined with palmitoyl-CoA, and released. Unattached carnitine is then shuttled back to the cytosolic side of mitochondrial membrane.
Beta-oxidation
Once inside the mitochondrial matrix, palmitoyl-CoA may undergo β-oxidation. The full oxidation of palmitic acid (or palmitoyl-CoA) results in 8 acetyl-CoA's, 7 NADH, 7 {{chem2|H+}}, and 7 FADH2.{{Citation|last1=Kamel|first1=Kamel S.|title=Ketoacidosis|date=2017|work=Fluid, Electrolyte and Acid-Base Physiology|pages=99–139|publisher=Elsevier|isbn=978-0-323-35515-5|last2=Halperin|first2=Mitchell L.|doi=10.1016/b978-0-323-35515-5.00005-1}} The full reaction is below:
:{{Chem2 | Palmitoyl\-CoA + 7 CoA\-SH + 7 NAD+ + 7 FAD -> 8 Acetyl\-CoA + 7 NADH + 7 H+ + 7 FADH2 }}
Sphingolipid biosynthesis
Palmitoyl-CoA is also the starting substrate, along with serine, for sphingolipid biosynthesis. Palmitoyl CoA and serine participate in a condensation reaction catalyzed by serine C-palmitoyltransferase (SPT), in which 3-ketosphinganine is formed. These reactions occur in the cytosol.{{Cite journal|last1=Michel|first1=Christoph|last2=van Echten-Deckert|first2=Gerhild|date=1997-10-20|title=Conversion of dihydroceramide to ceramide occurs at the cytosolic face of the endoplasmic reticulum|journal=FEBS Letters|volume=416|issue=2|pages=153–155|doi=10.1016/s0014-5793(97)01187-3|pmid=9369202|s2cid=467943|issn=0014-5793|doi-access=|bibcode=1997FEBSL.416..153M }}
:Image:Sphingosine synthesis corrected.png{{clear-left}}
Additional images
Image:Sphk1 diag b.jpg|Synthesis
Image:Palmitic acid.png|Palmitic acid
Image:Coenzym A.svg|Coenzyme A
See also
- Coenzyme A (CoA)
References
{{Reflist|2}}
{{Lysophospholipid signaling}}
{{DEFAULTSORT:Palmitoyl-Coa}}