A Nonketotic Hyperglycinemia Mouse Shows Wide-Ranging Biochemical Consequences of Elevated Glycine, Reduced Folate One-Carbon Charging, and Serine Deficiency.

ABSTRACT: Nonketotic hyperglycinemia is a severe neonatal epileptic encephalopathy caused by deficient glycine cleavage enzyme activity, for which currently no effective treatment exists. Incomplete understanding of brain biochemistry represents a major knowledge gap to develop new treatments. We examined the biochemistry in blood, liver, cortex, hippocampus, and cerebellum of a mouse model homozygous for the Gldc variant p.Ala394Val. Glycine was increased in all compartments and caused increased brain neurotoxic metabolites guanidinoacetate and methylglyoxal, and also N-acetylglycine and cystathionine. The glycine extruding transporter Slc6a20 was increased. There was reduced one-carbon folate charging with secondarily reduced methionine in the cortex, and reduced alternative one-carbon donors L-se

SUBMITTER: Swanson MA 

PROVIDER: S-EPMC12848846 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature