The following enzymes with malonyl-CoA synthetase activity are known:
Acyl-CoA synthetase family member 3 (ACSF3) The only known malonyl-CoA synthetase in
mammals is the
mitochondrial enzyme
acyl-CoA synthetase family member 3 (ACSF3), which, in addition to malonate, also accepts
methylmalonate as a
substrate with approximately 70% efficiency. ACSF3 is required for the clearance of intramitochondrial malonate, as malonate is a potent
inhibitor of mitochondrial respiration through the
competitive inhibition of
succinate dehydrogenase (Complex II), an enzyme that simultaneously functions in the
citric acid cycle and the
respiratory chain. In addition to the mitochondrial
isoform of
acetyl-CoA carboxylase 1 (mtACC1), which produces malonyl-CoA from acetyl-CoA, ACSF3 hereby contributes to the mitochondrial malonyl-CoA pool required for
mitochondrial fatty acid synthesis,
lysine malonylation, acetyl-CoA synthesis, and incorporation into cellular lipids. Malonyl-CoA is required as a substrate in
acylation and
condensation reactions. AAE13 is localized both in the
cytosol and in the mitochondria, whereby the cytosolic
isoform is not essential, as cytosolic malonyl-CoA is sufficiently provided by cytosolic
acetyl-CoA carboxylase. In contrast, the mitochondrial isoform is essential for plant growth. == Clinical relevance ==