Malonyl-CoA

Malonyl-CoA
Names
	Preferred 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-3λ5,5λ5-diphosphahenicosan-21-oic acid
Identifiers
CAS Number	524-14-1(free acid); 116928-84-8(tetralithium salt);
ChemSpider	559121;
ECHA InfoCard	100.007.596
MeSH	Malonyl+CoA
PubChemCID	644066;
UNII	LNB9YCJ9F9(free acid);
CompTox Dashboard(EPA)	DTXSID40904351;
	InChI 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 Key: LTYOQGRJFJAKNA-DVVLENMVSA-N;
Properties
Chemical formula	C24H38N7O19P3S
Molar mass	853.582
	Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa). verify(what is?) Infobox references

Malonyl-CoAis acoenzyme Aderivative ofmalonic acid.

Functions

It plays a key role in chain elongation infatty acid biosynthesisandpolyketidebiosynthesis.

Cytosolic fatty acid biosynthesis

Malonyl-CoA provides 2-carbon units to fatty acids and commits them to fatty acid chain synthesis.

Malonyl-CoA is formed by carboxylatingacetyl-CoAusing the enzymeacetyl-CoA carboxylase.One molecule of acetyl-CoA joins with a molecule ofbicarbonate,^[1]requiring energy rendered fromATP.

Malonyl-CoA is utilised in fatty acid biosynthesis by the enzymemalonyl coenzyme A:acyl carrier protein transacylase(MCAT). MCAT serves to transfermalonatefrom malonyl-CoA to the terminalthiolofholo-acyl carrier protein(ACP).

Mitochondrial fatty acid synthesis

Malonyl-CoA is formed in the first step ofmitochondrialfatty acid synthesis (mtFASII) frommalonic acidby malonyl-CoA synthetase (ACSF3).^[2]^[3]

Polyketide biosynthesis

MCAT is also involved in bacterialpolyketidebiosynthesis. The enzyme MCAT together with an acyl carrier protein (ACP), and apolyketide synthase(PKS) and chain-length factor heterodimer, constitutes the minimal PKS of type II polyketides.

Regulation

Malonyl-CoA is a highly regulated molecule in fatty acid synthesis; as such, it inhibits the rate-limiting step inbeta-oxidationof fatty acids. Malonyl-CoA inhibitsfatty acidsfrom associating withcarnitineby regulating the enzymecarnitine acyltransferase,thereby preventing them from entering themitochondria,wherefatty acid oxidationand degradation occur.

Related diseases

Malonyl-CoA plays a special role in the mitochondrial clearance of toxic malonic acid in the metabolic disordercombined 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 bymalonyl-CoA decarboxylase.^[2]^[4]In contrast, in CMAMMA due tomalonyl-CoA decarboxylase deficiency,malonyl-CoA decarboxylase is decreased, which converts malonyl-CoA to acetyl-CoA.^[4]

$\mathrm {Malonic\ acid+CoA+ATP\ {\xrightarrow[{ACSF3}]{Malonyl{-}CoA\ Synthetase}}\ Malonyl{-}CoA\ {\xrightarrow[{MLYCD}]{Malonyl-CoA\ Decarboxylase}}\ Acetyl{-}CoA}$

References

^Nelson D, Cox M (2008).Lehninger principles of biochemistry(5th ed.). p. 806.
^^a ^bWitkowski, 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.
^^a ^b ^cBowman, 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 links

Hope for new way to beat obesity

[1] Nelson D, Cox M (2008).Lehninger principles of biochemistry(5th ed.). p. 806.

[:1-2] 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.PMC3190830.PMID 21846720.

[3] 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.

[:0-4] 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.PMC6347522.PMID 30201289.

[1]

[2]

[3]

[4]