SAHH (S-Adenosylhomocysteine Hydrolase)
Enzyme that cleaves SAH into homocysteine and adenosine; reversible reaction dependent on product removal.

S-Adenosylhomocysteine Hydrolase (SAHH, also called AHCY) catalyzes the reversible hydrolysis of S-adenosylhomocysteine (SAH) to homocysteine and adenosine. Importantly, the equilibrium of this reaction actually favors SAH synthesis, meaning the reaction only proceeds toward homocysteine production when the products (homocysteine and adenosine) are rapidly removed.
This makes downstream metabolism critical: if homocysteine accumulates (due to B12, folate, or B6 deficiency) or adenosine accumulates, the reaction reverses and SAH builds up, inhibiting methylation.
SAHH is zinc-dependent and NAD+-dependent. SAHH deficiency causes severe hypermethioninemia and developmental delay.
Metabolic Connections
SAHH (S-Adenosylhomocysteine Hydrolase) connects to 7 other pathways.
Methylation

Homocysteine
Homocysteine is produced by SAHH; its removal drives the reaction forward
Sulfur-containing amino acid at the crossroads of methylation. Elevated levels indicate impaired methylation or B-vitamin deficiency.

Homocysteine
SAHH cleaves SAH to produce homocysteine; reaction is reversible and product-dependent
Sulfur-containing amino acid at the crossroads of methylation. Elevated levels indicate impaired methylation or B-vitamin deficiency.
Cofactors

NAD+
NAD+ is a required cofactor for SAHH enzyme activity
Nicotinamide adenine dinucleotide - essential coenzyme for energy metabolism, DNA repair, and sirtuin activation.

NAD+
SAHH requires NAD+ as cofactor for cleaving SAH
Nicotinamide adenine dinucleotide - essential coenzyme for energy metabolism, DNA repair, and sirtuin activation.
Metabolites

S-Adenosylhomocysteine (SAH)
SAHH cleaves SAH to produce homocysteine and adenosine
Product of SAMe after methyl group donation; must be rapidly converted to homocysteine to prevent methylation inhibition.

S-Adenosylhomocysteine (SAH)
SAHH enzyme converts SAH to homocysteine; this reaction is reversible and equilibrium-dependent
Product of SAMe after methyl group donation; must be rapidly converted to homocysteine to prevent methylation inhibition.
