alphamethylacylCoA

Alpha-methylacyl-CoA refers to a class of CoA thioester intermediates in fatty acid metabolism that bear a methyl group at the alpha position relative to the carbonyl. These alpha-methylacyl-CoA esters are derived from branched-chain fatty acids such as phytanic acid and pristanic acid after activation to CoA thioesters, and they participate in subsequent oxidation steps in peroxisomes and mitochondria.

A central enzyme in the metabolism of these compounds is alpha-methylacyl-CoA racemase (AMACR). AMACR catalyzes the racemization of the two enantiomers of alpha-methylacyl-CoA esters, allowing the beta-oxidation machinery to process both forms. This racemization is important because certain branched-chain fatty acids, which cannot be efficiently degraded by beta-oxidation without this step, rely on AMACR to enable their complete breakdown.

Pathway context involves the overall catabolism of phytanic and pristanic acids. Phytanic acid, for example, first undergoes alpha-oxidation to remove its methyl branch, producing substrates that can enter beta-oxidation with the help of AMACR. Proper function of this pathway is essential for preventing accumulation of branched-chain fatty acids and their CoA derivatives, which can disrupt cellular function, particularly in nervous system tissues.

Clinical significance of alphamethylacyl-CoA metabolism lies in AMACR deficiency, a rare inherited disorder caused by mutations in the AMACR gene. The condition typically presents with adult-onset neurodegeneration and white matter abnormalities. Biochemical features include elevated levels of phytanic and pristanic acids and abnormal excretion of alpha-methyl-branched fatty acids. Diagnosis is confirmed by genetic testing, and management focuses on dietary restriction of phytanic acid-containing foods and supportive care.