title: Promiscuous activity of arginine:glycine amidinotransferase is responsible for the synthesis of the novel cardiovascular risk factor homoarginine.
abstract: Low plasma homoarginine has emerged as a risk marker for cardiovascular disease. We exploited cells of a patient with a rare inborn error of metabolism to explore potential pathways of homoarginine synthesis, using stable isotopes and mass spectrometry. Control lymphoblasts, as opposed to lymphoblasts from an arginine:glycine amidinotransferase (AGAT)-deficient patient, were able to synthesize homoarginine from arginine and lysine. In contrast, in a patient with a deficiency of the urea cycle enzyme argininosuccinate synthase, plasma homoarginine was not decreased. We conclude that promiscuous activity of AGAT, a key enzyme in creatine synthesis, plays a pivotal role in homoarginine synthesis.
authors.affiliation: Metabolic Laboratory, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mariska
authors.initials: M
authors.lastname: Davids
authors.forename: Joseph D T
authors.initials: JD
authors.lastname: Ndika
authors.forename: Gajja S
authors.initials: GS
authors.lastname: Salomons
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Blom
authors.forename: Tom
authors.initials: T
authors.lastname: Teerlink
mesh_terms: D000579:Amidinotransferases / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism*; D002658:Developmental Disabilities / Q000097:blood / Q000378:metabolism; D006709:Homoarginine / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000097:blood / Q000378:metabolism; D008297:Male; D012307:Risk Factors; D013064:Speech Disorders / Q000097:blood / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D006709:Homoarginine; D000579:Amidinotransferases; C020681:glycine amidinotransferase