AHCY - Adenosylhomocysteinase (Like) | Elisa - Clia - Antibody - Protein

Background:

Adenosylhomocysteinase (AHCY) is an enzyme crucial for maintaining cellular methylation balance by catalyzing the hydrolysis of S-adenosylhomocysteine (SAH) into adenosine and homocysteine. This reaction is essential for recycling adenosine and homocysteine, as well as for regulating S-adenosylmethionine (SAM) levels, a key methyl donor in numerous biological processes. AHCY plays a critical role in epigenetic regulation, gene expression, and cellular metabolism. Dysregulation of AHCY activity has been associated with various diseases, including cancer, cardiovascular disorders, and neurodegenerative conditions. Understanding the molecular mechanisms underlying AHCY function provides insights into cellular methylation pathways and their implications for human health and disease. Research into AHCY regulation offers potential targets for therapeutic intervention in diseases related to methylation imbalance. Ongoing studies continue to unravel the complex roles of AHCY in cellular physiology and pathology.

Protein Structure:

• Molecular Weight: Approximately 48 kDa per monomer, with the functional enzyme being a homotetramer.
• Primary Structure: AHCY consists of about 432 amino acids per subunit.
• Domains: The enzyme contains nucleotide-binding domains that interact with adenosine and homocysteine.
• Subcellular Localization: AHCY is primarily localized in the cytoplasm but can also be found in the nucleus.
• Secondary and Tertiary Structures: The enzyme features alpha-helices and beta-sheets, forming a compact structure essential for its enzymatic activity. The active site is formed by residues from adjacent monomers in the tetrameric assembly.

Classification and Subtypes:

• Enzyme Classification: AHCY is classified under EC 3.3.1.1.
• Isoforms: While the primary form of AHCY is the most studied, alternative splicing can result in different isoforms with varied regulatory properties.

Function and Biological Significance:

• Methionine Cycle: AHCY plays a pivotal role in the methionine cycle, influencing cellular methylation capacity by regulating the levels of SAH and homocysteine.
• Methylation Reactions: By converting SAH to homocysteine and adenosine, AHCY prevents the inhibition of methyltransferases, ensuring proper methylation of DNA, RNA, proteins, and lipids.
• Homocysteine Regulation: The enzyme indirectly controls homocysteine levels, which are critical as elevated homocysteine is associated with cardiovascular diseases and other metabolic disorders.

Interactions:

• Cofactors: AHCY requires NAD+ as a cofactor for its enzymatic activity.
• Substrates: The primary substrate for AHCY is S-adenosylhomocysteine (SAH).
• Protein-Protein Interactions: AHCY interacts with various proteins involved in methylation and metabolic pathways, influencing their function and regulation.

Clinical Issues:

• Hyperhomocysteinemia: Defects in AHCY can lead to hyperhomocysteinemia, characterized by high levels of homocysteine in the blood, which is a risk factor for cardiovascular diseases, stroke, and thromboembolism.
• Inherited AHCY Deficiency: This rare genetic disorder can lead to developmental delays, myopathy, and liver dysfunction due to impaired methylation processes.
• Cancer: Aberrant methylation due to AHCY dysfunction can lead to oncogene activation and tumor suppressor gene silencing, contributing to cancer development.
• Neurodegenerative Diseases: Impaired methylation due to AHCY deficiency has been linked to neurodegenerative diseases like Alzheimer's and Parkinson's disease.

Summary:

Adenosylhomocysteinase (AHCY) is an essential enzyme in the methionine cycle, responsible for hydrolyzing S-adenosylhomocysteine (SAH) to homocysteine and adenosine. This process is crucial for maintaining cellular methylation reactions. AHCY's role in regulating methylation and homocysteine levels highlights its significance in cardiovascular health, metabolic disorders, cancer, and neurodegenerative diseases. Understanding AHCY's function and its implications in various diseases can provide insights into potential therapeutic targets and strategies for managing these conditions.