Arginine:glycine amidinotransferase (AGAT) (AGAT)

Arginine:glycine amidinotransferase (AGAT) is a mitochondrial enzyme that catalyzes the initial and rate-limiting step of creatine biosynthesis [UniProt: P50440]. It functions by transferring an amidino group from L-arginine to glycine, producing guanidinoacetate (GAA) and L-ornithine [PubMed: 10951540]. This enzyme is primarily expressed in the kidney and pancreas, providing the precursor GAA which is subsequently methylated in the liver to form creatine, a critical component for cellular energy buffering in the brain and skeletal muscle [NCBI Gene: 2628]. Genetic mutations in the GATM gene result in AGAT deficiency, a rare metabolic disorder known as Cerebral Creatine Deficiency Syndrome 3, which manifests as severe intellectual disability and developmental delays [OMIM: 602360]. Therapeutic strategies currently focus on oral creatine supplementation to restore systemic creatine levels and bypass the enzymatic defect [PubMed: 23660395]. Beyond its role in rare diseases, AGAT has been implicated in broader metabolic contexts, including potential associations with chronic kidney disease and statin-induced myopathy [PubMed: 23995135].

Other names

L-arginine:glycine amidinotransferaseGlycine amidinotransferaseGATMTransamidinase

Catalyzes the transfer of an amidino group from L-arginine to glycine to form guanidinoacetate and L-ornithine, serving as the rate-limiting step in creatine biosynthesis [UniProt: P50440].