Glycine amidinotransferase

Table 7.2.5 Pathological values for Cr and GA. AGAT L-Arginine glycine amidinotransferase, GAMT guanidinoacetate methyltransferase...

Diagnostic enzyme assay that uses stable-isotope-labeled substrates to detect L-argi-nine glycine amidinotransferase deficiency. Clin Chem 49 803-805... 

Item CB, Stockler-Ipsiroglu S, Stromberger C, Muhl A, Alessandri MG, Bianchi MC, et al. Arginine glycine amidinotransferase deficiency the third inborn error of creatine metabolism in humans. Am J Hum Genet 2001 69 1127-33. 

The catalytic mechanism of L-arginine glycine amidinotransferase (AGAT) is a representative example. AGAT catalyzes the first step in the synthesis of creatine, which along with phosphocreatine, is an important energy reservoir in the body. The catalytic machinery is the same as that found in the hydrolases, but the substrate is repositioned in the active site so that a different C -N bond is broken. An activated urea covalent intermediate is formed and used in the subsequent reaction with glycine. 

Figure 30 The creatine (42) biosynthesis pathway consists of two enzymes L-arginine glycine amidinotransferase (AGAT) and guanidinoacetate A/-methyltransferase (GAMT). Atoms derived from glycine are shown in green, arginine in blue, and S-adenosylmethionine (AdoMet) in black.

Figure 31 Structure of L-arginine glycine amidinotransferase in complex with L-ornithine. A modified pentein fold can be seen in a top view (a) and the side view (b), with large sequence inserts found in the first and second subdomains. The bound L-ornithine inhibitor, shown asa ball-and-stick model, marks the substrate-binding site. This figure was prepared using coordinates from PDB accession code 3JDW.

Figure 32 Closed (tan) and open (blue) conformations of L-arginine glycine amidinotransferase complexed with L-arginine (blue) and glycine (tan), respectively. Ligands are shown in ball-and-stick model, and the proteins are shown using ribbon models. The figure was constructed using coordinates from PDB accession codes 4JDW and 5JDW, respectively.

Glycine amidinotransferase 2 guanidinoacetate methyltransferase 3 creatininase 4 creatine kinase... 

Fig. 24.1. Metabolic pathway of creatine/creatine-phosphate. AGAT, arginine glycine amidinotransferase GAMT, guanidinoacetate methyltransferase CRTR, creatine transporter CK, creatine kinase...

Table 24.2. Arginine glycine amidinotransferase (AGAT) deficiency n=2 [16]...

Muenchhoff J., Siddiqui, K.S., Poljak, A., Raftery, M.J., Barrow, K.D., and Neilan, B.A. (2010) A novel prokaryotic L-arginine glycine amidinotransferase is involved in cylindrospermopsin biosynthesis. FEES J., 277, 3844-3860. 

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