AMACR

AMACR (Alpha-Methylacyl-CoA Racemase) is an enzyme that plays a crucial role in the metabolism of branched-chain fatty acids and bile acid intermediates. It is encoded by the AMACR gene in humans.

Function

AMACR is involved in the β-oxidation of branched-chain fatty acids and bile acid intermediates. It catalyzes the racemization of 2-methyl-branched fatty acyl-CoA esters, converting (R)-2-methylacyl-CoA to (S)-2-methylacyl-CoA, which is a necessary step for the subsequent β-oxidation process. This enzyme is essential for the proper metabolism of dietary branched-chain fatty acids and the synthesis of bile acids from cholesterol.

Clinical Significance

AMACR has been identified as a biomarker for certain types of cancer, particularly prostate cancer. Elevated levels of AMACR expression have been observed in prostate cancer tissues compared to normal prostate tissues. This makes it a useful diagnostic marker in the pathology of prostate cancer. Mutations in the AMACR gene can lead to metabolic disorders such as Adult Refsum disease and bile acid synthesis defects. These conditions are characterized by the accumulation of branched-chain fatty acids and bile acid intermediates, leading to various clinical symptoms.

Structure

The AMACR enzyme is a homodimer, meaning it consists of two identical subunits. Each subunit contains an active site that is responsible for the racemization reaction. The enzyme is localized in the peroxisome and mitochondrion, where it performs its metabolic functions.

Related Enzymes

AMACR is part of a larger family of enzymes involved in fatty acid metabolism. Other related enzymes include Acyl-CoA dehydrogenase, Enoyl-CoA hydratase, and 3-hydroxyacyl-CoA dehydrogenase. These enzymes work in concert to facilitate the β-oxidation of fatty acids.

Research and Developments

Ongoing research is focused on understanding the precise mechanisms of AMACR in fatty acid metabolism and its role in cancer biology. Studies are also exploring the potential of AMACR as a therapeutic target for cancer treatment.

See Also

• Prostate cancer
• Adult Refsum disease
• Bile acid synthesis defects
• Fatty acid metabolism
• Peroxisome
• Mitochondrion