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   » » Wiki: Malonyl-coa
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Malonyl-CoA is a derivative of .


Biosynthesis
Malonyl-CoA cannot cross membranes and there is no known malonyl-CoA import mechanism. The therefore takes place locally:

  • : Malonyl-CoA is formed by using the highly regulated enzyme (ACC1). One molecule of acetyl-CoA joins with a molecule of , requiring energy rendered from ATP.
  • Mitochondrial outer membrane: Malonyl-CoA is formed by carboxylating using the highly regulated enzyme (ACC2). The reaction is the same as with ACC1.
  • mitochondrial matrix: Malonyl-CoA is formed in coordinated fashion by mtACC1, a mitochondrial of ACC1, and acyl-CoA synthetase family member 3 (ACSF3), a mitochondrial malonyl-CoA synthetase. MtACC1, like cytosolic ACC1 catalyses the carboxylation of acetyl-CoA, while ACSF3 catalyses the ification of to . The latter serves for the clearance of mitochondrial malonate, since malonate is a potent inhibitor of mitochondrial respiration as it competitively inhibits succinate dehydrogenase. However, the source of malonyl-CoA in the is still up for debate.


Functions
It plays a key role in chain elongation in fatty acid biosynthesis and biosynthesis.


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

Malonyl-CoA is utilised in fatty acid biosynthesis by the enzyme (MCAT). MCAT serves to transfer from malonyl-CoA to the terminal of holo-acyl carrier protein (ACP).

Malonyl-CoA is a highly regulated molecule in fatty acid synthesis; as such, it inhibits the rate-limiting step in of fatty acids. Malonyl-CoA inhibits from associating with by regulating the enzyme carnitine palmitoyltransferase, thereby preventing them from entering the , where fatty acid oxidation and degradation occur.


Polyketide biosynthesis
MCAT is also involved in bacterial 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.


Clinical relevance
Malonyl-CoA plays a special role in the mitochondrial clearance of toxic malonic acid in the metabolic disorders combined malonic and methylmalonic aciduria (CMAMMA) and . In CMAMMA, malonyl-CoA synthetase, ACSF3 is impaired, which generates mitochondrial malonyl-CoA from malonic acid, which can then be converted to acetyl-CoA by malonyl-CoA decarboxylase. In contrast, in , malonyl-CoA decarboxylase is decreased, which converts malonyl-CoA to acetyl-CoA.

\mathrm{Malonic\ acid + CoA + ATP\ \xrightarrowACSF3{Malonyl{-}CoA\ Synthetase} \ Malonyl{-}CoA \ \xrightarrowMLYCD{Malonyl-CoA\ Decarboxylase} \ Acetyl{-}CoA }


See also
  • MCAT (gene)


External links

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