Human glycine N-methyltransferase mutations provide insight into its role in methionine metabolism

Two Italian siblings with mild liver disease carry two distinct mutations in the gene encoding Glycine N-methyltransferase (GNMT).

• GNMT is a key enzyme in the liver that uses S-adenosylmethionine to methylate glycine, producing N-methylglycine and S-adenosylhomocysteine.
• This enzyme may help regulate methyl group levels in the body by converting excess S-adenosylmethionine to S-adenosylhomocysteine.
• GNMT activity is inhibited by 5-methyltetrahydrofolate pentaglutamate, linking its function to dietary methionine availability.
• The identified mutations in GNMT are not due to common polymorphisms, indicating they may have a specific impact on enzyme function.

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