Glycine amidinotransferase (GATM) (GATM)

Glycine amidinotransferase (GATM), also known as L-arginine:glycine amidinotransferase (AGAT), is a mitochondrial enzyme that catalyzes the first and rate-limiting step of creatine biosynthesis by transferring an amidino group from arginine to glycine to form guanidinoacetate (GAA) (UniProt P50440). This process is vital for maintaining cellular energy stores, particularly in the brain and muscles, where creatine acts as a critical ATP buffer (MedlinePlus). Mutations in the GATM gene can lead to autosomal recessive AGAT deficiency, characterized by intellectual disability and muscle weakness, or an autosomal dominant form of renal Fanconi syndrome caused by the formation of toxic intramitochondrial protein aggregates (NIH). GATM is also recognized as a significant pharmacogenomic marker; specific genetic variants are associated with an increased risk of statin-induced myopathy due to their influence on GATM expression levels (Nature). Furthermore, GATM is being investigated as a therapeutic target in oncology and endometriosis, where its upregulation supports tumor progression and resistance to cell death (Heliyon). Current clinical management primarily involves creatine supplementation for deficiency states, while research into small-molecule inhibitors is ongoing for other indications.

Other names

AGATATCCDS3FRTS1L-arginine:glycine amidinotransferaseTransamidinaseMitochondrial glycine amidinotransferase

Substrate supplementation for deficiency states; competitive inhibition of enzymatic activity; pharmacogenomic modulation of expression levels.