Recombinant Human Malonyl-CoA decarboxylase, mitochondrial (MLYCD)

Function

Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In the fatty acid biosynthesis MCD selectively removes malonyl-CoA and thus assures that methyl-malonyl-CoA is the only chain elongating substrate for fatty acid synthase and that fatty acids with multiple methyl side chains are produced. In peroxisomes it may be involved in degrading intraperoxisomal malonyl-CoA, which is generated by the peroxisomal beta-oxidation of odd chain-length dicarboxylic fatty acids. Plays a role in the metabolic balance between glucose and lipid oxidation in muscle independent of alterations in insulin signaling. May play a role in controlling the extent of ischemic injury by promoting glucose oxidation

Subcellular Location

Cytoplasm; Mitochondrion matrix; Peroxisome; Peroxisome matrix

Disease Association

Malonyl-CoA decarboxylase deficiency (MLYCD deficiency) : Autosomal recessive disease characterized by abdominal pain, chronic constipation, episodic vomiting, metabolic acidosis and malonic aciduria. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in fibroblasts and hepatoblastoma cells (at protein level). Expressed strongly in heart, liver, skeletal muscle, kidney and pancreas. Expressed in myotubes. Expressed weakly in brain, placenta, spleen, thymus, testis, ovary and small intestine

Subunit

Homotetramer. Dimer of dimers. The two subunits within a dimer display conformational differences suggesting that at any given moment, only one of the two subunits is competent for malonyl-CoA binding and catalytic activity. Under oxidizing conditions, can form disulfide-linked homotetramers (in vitro). Associates with the peroxisomal targeting signal receptor PEX5

Pathway

Metabolic intermediate biosynthesis; acetyl-CoA biosynthesis; acetyl-CoA from malonyl-CoA: step 1/1

• FitzPatrick D.R. et al. The molecular basis of malonyl-CoA decarboxylase deficiency. — Am. J. Hum. Genet. (1999)
• Sacksteder K.A. et al. MCD encodes peroxisomal and cytoplasmic forms of malonyl-CoA decarboxylase and is mutated in malonyl-CoA decarboxylase deficiency. — J. Biol. Chem. (1999)
• Gao J. et al. Cloning and mutational analysis of human malonyl-coenzyme A decarboxylase. — J. Lipid Res. (1999)
• Martin J. et al. The sequence and analysis of duplication-rich human chromosome 16. — Nature (2004)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Zhou D. et al. Expression, purification, and characterization of human malonyl-CoA decarboxylase. — Protein Expr. Purif. (2004)
• Bouzakri K. et al. Malonyl CoenzymeA decarboxylase regulates lipid and glucose metabolism in human skeletal muscle. — Diabetes (2008)
• Ghosh D. et al. A proteome-wide perspective on peroxisome targeting signal 1(PTS1)-Pex5p affinities. — J. Am. Chem. Soc. (2010)