L-arginine:glycine amidinotransferase (AGAT) (AGAT)

L-arginine:glycine amidinotransferase (AGAT) is a mitochondrial enzyme that catalyzes the initial and rate-limiting step in creatine biosynthesis [UniProt P50440]. It functions by transferring a guanidino group from L-arginine to glycine, resulting in the formation of guanidinoacetate (GAA) and L-ornithine [NCBI Gene GATM]. This process primarily occurs in the kidneys and pancreas, after which GAA is transported to the liver for final conversion into creatine, a vital molecule for cellular energy homeostasis [PubMed PMID: 21302317]. Genetic mutations in the GATM gene lead to Cerebral Creatine Deficiency Syndrome type 3 (CCDS3), a condition characterized by intellectual disability, severe speech delay, and behavioral issues [OMIM 602360]. Therapeutic intervention for this deficiency typically involves oral creatine supplementation to bypass the enzymatic block and restore brain creatine levels [GeneReviews]. Additionally, AGAT expression levels have been linked to cardiovascular health, where its downregulation is observed in failing hearts, suggesting a potential role as a target for metabolic modulation in heart failure [Journal of Molecular and Cellular Cardiology, 2018]. The enzyme is also implicated in renal Fanconi syndrome, where specific mutations cause mitochondrial dysfunction and tubular damage [New England Journal of Medicine, 2013]. Research continues into AGAT as a biomarker for renal health and a potential therapeutic node for managing energy-related metabolic disorders.

Other names

Glycine amidinotransferaseGATMTransamidinaseArginine-glycine amidinotransferaseKidney amidinotransferase

Substrate replacement therapy to bypass enzymatic deficiency; metabolic modulation of the creatine synthesis pathway.