Arginine creatine synthesis

Arginine is the formamidine donor for creatine synthesis (Figure 31-6) and via ornithine to putrescine, spermine, and spermidine (Figure 31-3) Arginine is also the precursor of the intercellular signaling molecule ni-... 

D. Valine is an essential amino acid and is not synthesized in the human. Glydne reacts with sucdnyl CoA in the first step of heme synthesis and with arginine in the first step of creatine synthesis. The entire glycine molecule is incorporated into the growing purine ring. 

The presence of similar structural groups in their molecules led to much speculation and experimental work to demonstrate whether histidine could serve as a precursor for the synthesis of arginine, creatine, the purines, and the pyrimidines. These deductions have all been shown to be erroneous in the course of time. 

Figure 31-3. Arginine, ornithine, and proline metabolism. Reactions with solid arrows all occur in mammalian tissues. Putrescine and spermine synthesis occurs in both mammals and bacteria. Arginine phosphate of invertebrate muscle functions as a phosphagen analogous to creatine phosphate of mammalian muscle (see Figure 31-6).

Creatinine is formed in muscle from creatine phosphate by irreversible, nonenzymatic dehydration and loss of phosphate (Figure 31-6). The 24-hour urinary excretion of creatinine is proportionate to muscle mass. Glycine, arginine, and methionine all participate in creatine biosynthesis. Synthesis of creatine is completed by methylation of guanidoacetate by S-adenosylmethio-nine (Figure 31-6). 

The synthesis of creatine. In the kidney, guanidinoace-tate is produced from arginine and glycine, then released into the blood to be taken up by the liver and methylated to form creatine (Figure 8.20(a)). The creatine is, in turn, taken up by the muscle where it is phosphorylated to produce phosphocreatine, which can maintain the ATP level, especially in explosive exercise. Creatine and phosphocreatine are converted in muscle to creatinine, which is important in clinical practice (Figure 8.20(b)) (Box 8.3). 

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. 

Creatine is not a dietary essential as shown in Figure 14.5, it is synthesized from the amino acids glycine, arginine, and methionine. However, a single serving of meat will provide about 1 g of preformed creatine, whereas the average daily rate of de novo synthesis is 1 to 2 g, and endogenous synthesis is inhibited by a dietary intake. 

C) creatine requires glycine, arginine, and methionine for synthesis of its carbon skeleton... 

A. The amount of creatine in liver cells determines its rate of synthesis from glycine, arginine, and SAM. In muscle, creatine is converted to creatine phosphate, which is nonenzymati-cally cyclized to form creatinine. The amount of creatinine excreted by the kidneys each day depends on body muscle mass. In kidney failure, the excretion of creatinine into the urine will be low. 

The positively charged guanidinium group attached to the S-carbon of arginine is stabilized by resonance between the two NH2 groups and has a pK value of 12.48. Arginine is utilized in the synthesis of creatine and it participates in the urea cycle (Chapter 17). 

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. 

F. 47.7. The synthesis of creatine from arginine, glycine, and S-adenosyl methionine. Synthesis originates in the kidney and is completed in the hver. 

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