Adenosylhomocysteinase (AHCY), also known as S-adenosyl-L-homocysteine hydrolase (SAHH), is a crucial enzyme in the methionine cycle. This enzyme is highly conserved across various species, including bacteria, plants, and mammals . The recombinant form of human AHCY is produced using advanced biotechnological methods to study its structure, function, and potential therapeutic applications.
AHCY is a cytoplasmic tetramer, with each subunit tightly bound to an NAD co-factor . The enzyme catalyzes the reversible hydrolysis of S-adenosyl-L-homocysteine (SAH) into adenosine and homocysteine . This reaction is vital because SAH is a potent inhibitor of methyltransferases, enzymes responsible for transferring methyl groups to various substrates, including DNA, RNA, and proteins .
The primary role of AHCY is to regulate the intracellular concentration of SAH, thereby facilitating methylation reactions. Methylation is essential for numerous biological processes, including gene expression, DNA repair, and protein function . By breaking down SAH, AHCY ensures that methyltransferases can function efficiently, maintaining cellular homeostasis.
Recombinant human AHCY is typically produced in Escherichia coli (E. coli) systems. The recombinant protein often includes an N-terminal His-tag to facilitate purification . The purified enzyme is used in various research applications, including studies on enzyme kinetics, inhibitor screening, and structural analysis.
Deficiency in AHCY activity is associated with a rare genetic disorder known as AHCY deficiency. This condition leads to elevated levels of SAH and reduced methylation capacity, resulting in developmental delays, liver dysfunction, and other severe symptoms . Understanding the function and regulation of AHCY is crucial for developing potential therapeutic strategies for this and other related disorders.
Recombinant AHCY is a valuable tool in biochemical and medical research. It is used to study the enzyme’s role in the methionine cycle, its interaction with other cellular components, and its potential as a therapeutic target. Additionally, AHCY inhibitors are being explored for their potential in treating diseases characterized by aberrant methylation patterns, such as cancer and neurodegenerative disorders .