Guanidinoacetate methylation

Guanidinoacetate methyl-transferase (GAMT) defi dency Liver virus-transformed lymphoblasts cultured fibroblasts cultured amnio-cytes 19pl3J 601240... 

Stockier, S. and E Hanefeld, Guanidinoacetate methyl transferase deficiency a newly recognized inborn error of creatine biosynthesis. Wiener Klinische Wochenschrift, 109 86-88, 1997. 

Figure 8.20 (a) The synthesis of phosphocreatine. The compound guanidinoacetate is formed from arginine and glycine in the kidney and is then transported to the liver where it is methylated addition of CHj (see Chapter 15) to form creatine (see Appendix 8.4 for details). Creatine is taken up by tissues/ organs/cells and phosphorylated to form phosphocreatine, particularly in muscle, (b) Conversion of phosphocreatine and creatine to creatinine in muscle. Creatinine is gradually formed and then released into blood and excreted in urine. 

Since the overall reaction of cyclosporin formation is a very complex process (at least 40 single reactions), for the investigation of the A-methylation reaction, the formation of the diketopiperazines cyclo(D-alanine-A-methylleucine) and cyclo (L-alanine-A-methylleucine) was used. In contrast to other A-methyltrans-ferases such as guanidinoacetate methyltransferase [94] or indolethylamine meth-yltransferase [95], in which AdoHcy acts as a competitive inhibitor, in the case... 

The urea cycle intermediate arginine can be condensed with glycine to form guanidinoacetate, which in turn is methylated by the methyl donor S-adenosyl methionine to creatine. The creatine is then phosphorylated to form creatine phosphate, a high-energy store found in muscle. 

The first reaction in creatinine formation is the transfer of the amido (or amidine) group of arginine to glycine, forming guanidinoacetate. Subsequently, a methyl group is transferred from the ubiquitous 1-carbon-donor S-adenosylmethionine to guanidinoacetate to produce creatine (from which phosphocreatine is formed), some of which spontaneously cyclizes to creatinine, and is eliminated in the urine. 

Creatine is synthesized in the kidneys, liver, and pancreas by two enzymatically mediated reactions. In the first, transami-dation of arginine and glycine forms guanidinoacetic acid in the second, methylation of guanidinoacetic acid occurs with S-adenosylmethionine as the methyl donor. Creatine is then transported in blood to other organs, such as muscle and brain, where it is phosphorylated to phosphocreatine, a high-energy compound. 

Van Pilsum JF, Martin RP, Kito E. Determination of creatine, creatinine, arginine, guanidinoacetic acid, guanidine and methyl-guanidine in biological fluids. 

In the next step guanidinoacetate is methylated by S-adenosylmethionine by cytosolic S-adenosylmethionine guanidinoacetate-N-methyltransferase to form creatine. 

Creatine is synthesized in an interorgan metabolic pathway that spans the kidney and liver. In the kidney, arginine and glycine are condensed to form guanidinoacetate, which is exported from the kidney and taken up by hepatocytes in which it is methylated. Creatine phosphate is chemically rmstable and spontaneously cyclizes to give creatinine and phosphate it cannot be reverted back to creatine, so it is a metabolic end product that is excreted in the urine. Because the size of the creatine phosphate pool is relatively constant, the amount of creatinine produced in 24 h is also relatively constant. Thus, the amoruit of creatinine excreted in the urine is used clinically to gauge renal excretory function. 

Norepinephrine is methylated in the presence of a specific enzyme (S-adenosylmethionine transferase) and a cofactor (S-adenosylmethionine) to form epinephrine. This reaction is analogous to the methyla-tion of guanidinoacetic acid, which occurs in liver. Two distinct enzyme reactions are involved methionine is converted to S-adenosylmethionine in the presence of a methionine-activating enzyme and ATP, in which reaction all the phosphates of ATP are lost, the terminal phosphorus of ATP is liberated as inorganic phosphate and the two internal phosphoryl groups yield pyrophosphate and (2) norepinephrine is then methylated in the presence of a specific enzyme S-adenosylmethionine transferase to form epinephrine. 

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