Malonyl-CoA is formed in the first step of mitochondrial fatty acid synthesis (mtFASII) from malonic acid by malonyl-CoA synthetase (ACSF3).[2][3]
Polyketide biosynthesisedit
MCAT is also involved in bacterial polyketide biosynthesis. The enzyme MCAT together with an acyl carrier protein (ACP), and a polyketide synthase (PKS) and chain-length factor heterodimer, constitutes the minimal PKS of type II polyketides.
Regulationedit
Malonyl-CoA is a highly regulated molecule in fatty acid synthesis; as such, it inhibits the rate-limiting step in beta-oxidation of fatty acids. Malonyl-CoA inhibits fatty acids from associating with carnitine by regulating the enzyme carnitine acyltransferase, thereby preventing them from entering the mitochondria, where fatty acid oxidation and degradation occur.
Related diseasesedit
Malonyl-CoA plays a special role in the mitochondrial clearance of toxic malonic acid in the metabolic disorder combined malonic and methylmalonic aciduria (CMAMMA).[4] In CMAMMA due to ACSF3, malonyl-CoA synthetase is decreased, which can generate malonyl-CoA from malonic acid, which can then be converted to acetyl-CoA by malonyl-CoA decarboxylase.[2][4] In contrast, in CMAMMA due to malonyl-CoA decarboxylase deficiency, malonyl-CoA decarboxylase is decreased, which converts malonyl-CoA to acetyl-CoA.[4]
^Nelson D, Cox M (2008). Lehninger principles of biochemistry (5th ed.). p. 806.
^ abWitkowski, Andrzej; Thweatt, Jennifer; Smith, Stuart (September 2011). "Mammalian ACSF3 Protein Is a Malonyl-CoA Synthetase That Supplies the Chain Extender Units for Mitochondrial Fatty Acid Synthesis". Journal of Biological Chemistry. 286 (39): 33729–33736. doi:10.1074/jbc.M111.291591. ISSN 0021-9258. PMC3190830. PMID 21846720.
^Bowman, Caitlyn E.; Rodriguez, Susana; Selen Alpergin, Ebru S.; Acoba, Michelle G.; Zhao, Liang; Hartung, Thomas; Claypool, Steven M.; Watkins, Paul A.; Wolfgang, Michael J. (2017). "The Mammalian Malonyl-CoA Synthetase ACSF3 Is Required for Mitochondrial Protein Malonylation and Metabolic Efficiency". Cell Chemical Biology. 24 (6): 673–684.e4. doi:10.1016/j.chembiol.2017.04.009. PMC5482780. PMID 28479296.
^ abcBowman, Caitlyn E.; Wolfgang, Michael J. (January 2019). "Role of the malonyl-CoA synthetase ACSF3 in mitochondrial metabolism". Advances in Biological Regulation. 71: 34–40. doi:10.1016/j.jbior.2018.09.002. PMC6347522. PMID 30201289.
External linksedit
Hope for new way to beat obesity
December 03, 2023
malonyl, coenzyme, derivative, malonic, acid, namespreferred, iupac, name, amino, purin, hydroxy, phosphonooxy, oxolan, trihydroxy, pentaoxo, dimethyl, trioxa, thia, diaza, 3λ5, 5λ5, diphosphahenicosan, acididentifierscas, number, free, acid, y116928, tetralit. Malonyl CoA is a coenzyme A derivative of malonic acid Malonyl CoA NamesPreferred IUPAC name 9R 1 2R 3S 4R 5R 5 6 Amino 9H purin 9 yl 4 hydroxy 3 phosphonooxy oxolan 2 yl 3 5 9 trihydroxy 3 5 10 14 19 pentaoxo 8 8 dimethyl 2 4 6 trioxa 18 thia 11 15 diaza 3l5 5l5 diphosphahenicosan 21 oic acidIdentifiersCAS Number 524 14 1 free acid Y116928 84 8 tetralithium salt ChemSpider 559121 YECHA InfoCard 100 007 596MeSH Malonyl CoAPubChem CID 644066UNII LNB9YCJ9F9 free acid YCompTox Dashboard EPA DTXSID40904351InChI InChI 1S C24H38N7O19P3S c1 24 2 19 37 22 38 27 4 3 13 32 26 5 6 54 15 35 7 14 33 34 9 47 53 44 45 50 52 42 43 46 8 12 18 49 51 39 40 41 17 36 23 48 12 31 11 30 16 20 25 28 10 29 21 16 31 h10 12 17 19 23 36 37H 3 9H2 1 2H3 H 26 32 H 27 38 H 33 34 H 42 43 H 44 45 H2 25 28 29 H2 39 40 41 t12 17 18 19 23 m1 s1 YKey LTYOQGRJFJAKNA DVVLENMVSA N YPropertiesChemical formula C24H38N7O19P3SMolar mass 853 582Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Y verify what is Y N Infobox references Contents 1 Functions 1 1 Cytosolic fatty acid biosynthesis 1 2 Mitochondrial fatty acid synthesis 1 3 Polyketide biosynthesis 1 4 Regulation 2 Related diseases 3 See also 4 References 5 External linksFunctions editIt plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis Cytosolic fatty acid biosynthesis edit Malonyl CoA provides 2 carbon units to fatty acids and commits them to fatty acid chain synthesis Malonyl CoA is formed by carboxylating acetyl CoA using the enzyme acetyl CoA carboxylase One molecule of acetyl CoA joins with a molecule of bicarbonate 1 requiring energy rendered from ATP Malonyl CoA is utilised in fatty acid biosynthesis by the enzyme malonyl coenzyme A acyl carrier protein transacylase MCAT MCAT serves to transfer malonate from malonyl CoA to the terminal thiol of holo acyl carrier protein ACP Mitochondrial fatty acid synthesis edit Malonyl CoA is formed in the first step of mitochondrial fatty acid synthesis mtFASII from malonic acid by malonyl CoA synthetase ACSF3 2 3 Polyketide biosynthesis edit MCAT is also involved in bacterial polyketide biosynthesis The enzyme MCAT together with an acyl carrier protein ACP and a polyketide synthase PKS and chain length factor heterodimer constitutes the minimal PKS of type II polyketides Regulation edit Malonyl CoA is a highly regulated molecule in fatty acid synthesis as such it inhibits the rate limiting step in beta oxidation of fatty acids Malonyl CoA inhibits fatty acids from associating with carnitine by regulating the enzyme carnitine acyltransferase thereby preventing them from entering the mitochondria where fatty acid oxidation and degradation occur Related diseases editMalonyl CoA plays a special role in the mitochondrial clearance of toxic malonic acid in the metabolic disorder combined malonic and methylmalonic aciduria CMAMMA 4 In CMAMMA due to ACSF3 malonyl CoA synthetase is decreased which can generate malonyl CoA from malonic acid which can then be converted to acetyl CoA by malonyl CoA decarboxylase 2 4 In contrast in CMAMMA due to malonyl CoA decarboxylase deficiency malonyl CoA decarboxylase is decreased which converts malonyl CoA to acetyl CoA 4 M a l o n i c a c i d C o A A T P A C S F 3 M a l o n y l C o A S y n t h e t a s e M a l o n y l C o A M L Y C D M a l o n y l C o A D e c a r b o x y l a s e A c e t y l C o A displaystyle mathrm Malonic acid CoA ATP xrightarrow ACSF3 Malonyl CoA Synthetase Malonyl CoA xrightarrow MLYCD Malonyl CoA Decarboxylase Acetyl CoA nbsp See also editMCAT gene References edit Nelson D Cox M 2008 Lehninger principles of biochemistry 5th ed p 806 a b Witkowski Andrzej Thweatt Jennifer Smith Stuart September 2011 Mammalian ACSF3 Protein Is a Malonyl CoA Synthetase That Supplies the Chain Extender Units for Mitochondrial Fatty Acid Synthesis Journal of Biological Chemistry 286 39 33729 33736 doi 10 1074 jbc M111 291591 ISSN 0021 9258 PMC 3190830 PMID 21846720 Bowman Caitlyn E Rodriguez Susana Selen Alpergin Ebru S Acoba Michelle G Zhao Liang Hartung Thomas Claypool Steven M Watkins Paul A Wolfgang Michael J 2017 The Mammalian Malonyl CoA Synthetase ACSF3 Is Required for Mitochondrial Protein Malonylation and Metabolic Efficiency Cell Chemical Biology 24 6 673 684 e4 doi 10 1016 j chembiol 2017 04 009 PMC 5482780 PMID 28479296 a b c Bowman Caitlyn E Wolfgang Michael J January 2019 Role of the malonyl CoA synthetase ACSF3 in mitochondrial metabolism Advances in Biological Regulation 71 34 40 doi 10 1016 j jbior 2018 09 002 PMC 6347522 PMID 30201289 External links editHope for new way to beat obesity Retrieved from https en wikipedia org w index php title Malonyl CoA amp oldid 1157773838, wikipedia, wiki, book, books, library,
