Malonyl-CoA decarboxylase (MLYCD)

Malonyl-CoA decarboxylase (MLYCD) is a mitochondrial enzyme critical for controlling fatty acid oxidation by catalyzing the decarboxylation of malonyl-CoA into acetyl-CoA and carbon dioxide. This reaction is a key step in metabolic adaptation and energy homeostasis, especially in tissues like cardiac and skeletal muscle. The enzyme's activity maintains malonyl-CoA levels, which in turn inhibit carnitine palmitoyltransferase 1 (CPT1), thus controlling the rate of fatty acid entry into mitochondria for oxidation. MLYCD deficiency leads to accumulation of malonyl-CoA, causing clinical disorders such as malonic aciduria, hypoglycemia, and cardiomyopathy. It is an emerging therapeutic target for metabolic and cardiovascular disorders, although no approved drugs currently modulate its activity[1][2][3][5][7].

Other names

MLYCDMCDMalonyl-CoA carboxyl-lyaseMalonyl coenzyme A decarboxylasehMCDMalonyl-CoA decarboxylase, mitochondrial

Inhibition of malonyl-CoA decarboxylase would raise malonyl-CoA levels, potentially reducing fatty acid oxidation and modifying energy metabolism pathways. Activation lowers malonyl-CoA, promoting fatty acid oxidation. Drugs could act through direct enzymatic inhibition, RNA interference, or modulation of post-translational modifications affecting enzyme activity.