Determination of equilibria constants of arginine:glycine amidinotransferase (AGAT)-catalyzed reactions using concentrations of circulating amino acids

Amino Acids. 2023 Feb;55(2):203-213. doi: 10.1007/s00726-022-03218-5. Epub 2022 Dec 7.

Abstract

Arginine:glycine amidinotransferase (AGAT) catalyzes mainly two reactions that generate 1) L-homoarginine (hArg) from L-arginine and L-lysine (Kharg) and 2) guanidinoacetate (GAA) and L-ornithine from L-arginine and glycine (Kgaa). Previously, we found that pharmacological treatment of Becker muscular dystrophy (BMD) patients with metformin or L-citrulline resulted in antidromic effects on serum hArg and GAA concentrations, seemingly acting as an inhibitor and effector of AGAT activity, respectively. Here, we used data of this study as a model to determine Kharg and Kgaa values by using the concentrations of the participating amino acids measured in serum samples of the BMD patients. The study aimed to prove the general utility of this approach to investigate effects of amino acids and drugs on AGAT-catalyzed reactions in vivo in humans.

Keywords: AGAT; Citrulline; Equilibrium; Guanidinoacetate; Homoarginine; Lysine; Metformin; Ornithine; Supplementation.

MeSH terms

  • Amidinotransferases / metabolism
  • Arginine* / metabolism
  • Catalysis
  • Citrulline
  • Homoarginine
  • Humans
  • Muscular Dystrophy, Duchenne*

Substances

  • Arginine
  • glycine amidinotransferase
  • Homoarginine
  • Amidinotransferases
  • Citrulline