Disease relevance of Gamt

• Molecular cloning, sequence analysis, and expression in Escherichia coli of the cDNA for guanidinoacetate methyltransferase from rat liver [1].

High impact information on Gamt

• Five cDNA clones encoding rat liver guanidinoacetate methyltransferase (S-adenosyl-L-methionine: guanidinoacetate N-methyltransferase, EC 2.1.1.2) were isolated from a lambda gt11 cDNA library by use of a polyclonal antibody to the purified enzyme [1].
• Guanidinoacetate methyltransferase obeys an ordered Bi Bi mechanism in which AdoMet binds first [2].
• Rat guanidinoacetate methyltransferase has two aspartate residues (Asp-129 and Asp-134) conforming to the motif in close proximity to Tyr-136 that is photoaffinity-labeled by AdoMet (Takata, Y., and Fujioka, M. (1992) Biochemistry 31, 4369-4374) [2].
• Nucleotide sequence of the rat guanidinoacetate methyltransferase gene [3].
• Guanidinoacetate methyltransferase (GAMT) is the enzyme that catalyzes the last step of creatine biosynthesis [4].

Chemical compound and disease context of Gamt

• Rat liver guanidinoacetate methyltransferase, produced in Escherichia coli by recombinant DNA technique, possesses five cysteine residues per molecule [5].

Biological context of Gamt

• CrTr protein and mRNA expression, ATP, GAA, CK, GAMT, and protein tyrosine phosphorylation of CrTr were not significantly different between the two groups [6].
• CONCLUSION: Our results suggest that de novo synthesis of Cr by AGAT and GAMT, as well as cellular Cr uptake by CT1, are essential during embryonic development [7].
• GAMT has an alpha/beta open-sandwich structure, and the N-terminal section (residues 1-42) covers the active site entrance so that the active site is not visible [8].
• Recombinant rat liver guanidinoacetate methyltransferase is inactivated by glutathione disulfide (GSSG) following pseudo-first-order kinetics [9].

Anatomical context of Gamt

• AGAT and GAMT presented an ubiquitous neuronal and glial expression, whereas CRT1 was present in neurons and oligodendrocytes throughout the brain, but not in astrocytes [10].
• In order to better understand creatine synthesis and transport in the central nervous system (CNS), we studied the regional distribution of cells expressing AGAT, GAMT and the creatine transporter CRT1 in the adult rat brain by non-radioisotopic in situ hybridization [10].
• AGAT and CT1 are prominent in CNS, skeletal muscles and intestine, where they appear earlier than GAMT [7].
• RESULTS: We show that AGAT and GAMT are expressed in hepatic primordium as soon as 12.5 days, then progressively acquire their adult pattern of expression, with high levels of AGAT in kidney and pancreas, and high levels of GAMT in liver and pancreas [7].
• On the other hand, high levels of the mRNAs for both guanidinoacetate methyltransferase and Sadenosylhomocysteine hydrolase were expressed in the testis and epididymis as well as the liver and kidney [11].

Associations of Gamt with chemical compounds

• Guanidinoacetate methyltransferase (GAMT) activity, guanidinoacetic acid (GAA) content, creatine kinase (CK) activity, and creatinine (Crn) content were assayed luminometrically or spectrophotometrically [6].
• While creatine is mainly synthesized by the liver and the kidney, most of other tissues, including the brain, also express AGAT and GAMT [10].
• Creatine is synthesized from arginine by L-arginine:glycine amidinotransferase (AGAT) and S-adenosyl-L-methionine:N-guanidinoacetate methyltransferase (GAMT) and can be taken up by cells by creatine transporters (CRT) [10].
• Recombinant rat liver GAMT has been crystallized with S-adenosylhomocysteine (SAH), and the crystal structure has been determined at 2.5 A resolution [4].
• Recombinant rat guanidinoacetate methyltransferase: structure and function of the NH2-terminal region as deduced by limited proteolysis [12].

Physical interactions of Gamt

• An equilibrium binding study shows that guanidinoacetate methyltransferase in the free form binds AdoMet but not guanidinoacetate [12].

Regulatory relationships of Gamt

• Although guanidinoacetate methyltransferase is irreversibly inactivated upon ultraviolet irradiation in the absence of AdoMet, the enzyme inactivated by 1-h exposure to ultraviolet irradiation has been shown to bind AdoMet with an affinity identical to that of the native enzyme [13].

Other interactions of Gamt

• The aim of this work was to investigate the effect of guanidinoacetate (GAA), the principal metabolite accumulating in guanidinoacetate methyltransferase (GAMT)-deficiency, on Na(+), K(+)-ATPase, Mg(2+)-ATPase and acetylcholinesterase (AChE) activities in striatum of young rats [14].

Analytical, diagnostic and therapeutic context of Gamt

• Probing the S-adenosylmethionine-binding site of rat guanidinoacetate methyltransferase. Effect of site-directed mutagenesis of residues that are conserved across mammalian non-nucleic acid methyltransferases [15].
• Crystallization and preliminary x-ray diffraction studies of guanidinoacetate methyltransferase from rat liver [16].

References