AMACR - Alpha-methylacyl-CoA racemase | Elisa - Clia - Antibody - Protein

Background:

Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in the metabolism of fatty acids, particularly branched-chain fatty acids. It catalyzes the racemization of alpha-methyl-branched-chain fatty acyl-CoA esters, converting them from their R-isomer to their S-isomer or vice versa. AMACR is primarily localized within peroxisomes, cellular organelles involved in various metabolic processes, including the breakdown of fatty acids. It plays a crucial role in the β-oxidation pathway, which is responsible for breaking down fatty acids to generate energy. AMACR has gained significant attention in recent years due to its association with prostate cancer. It has been found to be overexpressed in prostate cancer cells compared to normal prostate tissue, and its expression levels have been correlated with tumor aggressiveness and disease progression. As such, AMACR is used as a diagnostic marker for prostate cancer, and its detection in tissue samples can aid in the diagnosis and classification of the disease. In addition to its role in prostate cancer, AMACR has also been implicated in other pathological conditions, including certain metabolic disorders. Mutations in the gene encoding AMACR can lead to disorders of fatty acid metabolism, such as alpha-methylacyl-CoA racemase deficiency, which is characterized by the accumulation of specific fatty acid metabolites and can result in neurological symptoms and developmental delays.

Protein Structure:

• Enzyme Classification: AMACR belongs to the family of racemases and epimerases, specifically those acting on hydroxy acids and derivatives.
• Active Sites: The enzyme contains active sites that facilitate the racemization (conversion) of (R)- and (S)-methyl-branched acyl-CoA substrates.
• Cofactors: AMACR functions with the assistance of cofactors such as FAD (flavin adenine dinucleotide) for its catalytic activity.

Classification and Subtypes:

• Isoforms: There are different isoforms of AMACR resulting from alternative splicing, which may vary in activity and tissue distribution.
• Gene Family: AMACR is a part of a broader family of enzymes involved in fatty acid metabolism.

Function and Biological Significance:

• Beta-Oxidation: AMACR plays a pivotal role in the beta-oxidation of branched-chain fatty acids and bile acid intermediates. It catalyzes the conversion of (R)-alpha-methylacyl-CoA to (S)-alpha-methylacyl-CoA, which can then be processed further in peroxisomes and mitochondria.
• Bile Acid Synthesis: It is essential in the synthesis of bile acids, particularly in the conversion of cholesterol to bile acids.
• Metabolic Regulation: By participating in the breakdown of branched-chain fatty acids, AMACR helps regulate lipid metabolism and energy production.

Interactions:

• Substrates: AMACR interacts with various substrates, including pristanic acid and bile acid intermediates.
• Pathways: It is involved in metabolic pathways related to fatty acid degradation and bile acid biosynthesis.

Clinical Issues:

• Prostate Cancer: AMACR is overexpressed in prostate cancer, making it a valuable biomarker for diagnosis and a potential target for therapeutic intervention.
• Other Cancers: Elevated levels of AMACR have also been observed in other cancers, such as colorectal and renal cancers.
• Inherited Disorders: Mutations in the AMACR gene can lead to conditions like adult-onset sensory motor neuropathy and a type of bile acid synthesis disorder.
• Diagnostic Marker: AMACR is used as an immunohistochemical marker in pathology to differentiate between malignant and benign prostate tissues.

Summary:

AMACR (Alpha-methylacyl-CoA racemase) is a critical enzyme in lipid metabolism, facilitating the racemization of branched-chain fatty acids and bile acid intermediates. Its role extends beyond basic metabolic functions to significant clinical implications, particularly in cancer diagnosis and therapy. Overexpression of AMACR in prostate and other cancers underscores its potential as a biomarker and therapeutic target. Mutations in the AMACR gene can lead to metabolic disorders, highlighting its importance in human health. Understanding the structure, function, and clinical relevance of AMACR continues to be a crucial area of research in biochemistry and medical science.