# Functional and Pathological Roles of AHCY

## TL;DR

This review discusses the enzyme AHCY, its role in methylation processes, and its importance in various organisms, including its connection to a rare human metabolic disorder.

## Contribution

The paper provides a comprehensive review of AHCY's evolutionary, biochemical, and functional aspects, highlighting recent and controversial findings.

## Key findings

- AHCY is essential for removing SAH, which is crucial for methyltransferase activity and transmethylation reactions.
- AHCY deletion is embryonic lethal in many organisms, showing its critical role in development.
- Human AHCY deficiency causes a rare, incurable metabolic disorder linked to methionine metabolism.

## Abstract

Adenosylhomocysteinase (AHCY) is a unique enzyme and one of the most conserved proteins in living organisms. AHCY catalyzes the reversible break of S-adenosylhomocysteine (SAH), the by-product and a potent inhibitor of methyltransferases activity. In mammals, AHCY is the only enzyme capable of performing this reaction. Controlled subcellular localization of AHCY is believed to facilitate local transmethylation reactions, by removing excess of SAH. Accordingly, AHCY is recruited to chromatin during replication and active transcription, correlating with increasing demands for DNA, RNA, and histone methylation. AHCY deletion is embryonic lethal in many organisms (from plants to mammals). In humans, AHCY deficiency is associated with an incurable rare recessive disorder in methionine metabolism. In this review, we focus on the AHCY protein from an evolutionary, biochemical, and functional point of view, and we discuss the most recent, relevant, and controversial contributions to the study of this enzyme.