Arginine transamination

Vitamin Ba (pyridoxine, pyridoxal, pyridoxamine) like nicotinic acid is a pyridine derivative. Its phosphorylated form is the coenzyme in enzymes that decarboxylate amino acids, e.g., tyrosine, arginine, glycine, glutamic acid, and dihydroxyphenylalanine. Vitamin B participates as coenzyme in various transaminations. It also functions in the conversion of tryptophan to nicotinic acid and amide. It is generally concerned with protein metabolism, e.g., the vitamin B8 requirement is increased in rats during increased protein intake. Vitamin B6 is also involved in the formation of unsaturated fatty acids. 

After formation of the aldimine, numerous factors in the enzyme facilitate deprotonation of the a-carbon (Fig. 3, Step II). The lysine liberated by transimi-nation is utilized as a general base and is properly oriented for effective deprotonation [11]. Furthermore, the inductive effects of the ring system are tuned to increase the stabilization of the quinoid intermediate. For example, the aspartate group that interacts with the pyridyl nitrogen of the co enzyme promotes proto-nation to allow the ring to act as a more effective electron sink. In contrast, in alanine racemase, a less basic arginine residue in place of the aspartic acid is believed to favor racemization over transamination [12]. 

Muscle activity involves processes such as aerobic and anaerobic glycolysis and is therefore accompanied by an increased pyruvate production. Consequently, the pyruvate transamination product alanine will be increased after exercise. Heavy exercise may be associated with an increased need of creatine biosynthesis from arginine. Ornithine is a by-product of this pathway and may be increased under these conditions. 

An essential step in the transamination reaction is the protonation of the quinonoid intermediate to form the external aldimine. The chirality of the amino acid formed is determined by the direction from which this proton is added to the quinonoid form. (Figure 24.10). This protonation step determines the 1 configuration of the amino acids produced. The interaction between the conserved arginine residue and the a-carboxylate group helps orient the substrate so that, when the lysine residue transfers a proton to the face of the quinonoid intermediate, it generates an aldimine with an 1 configuration at the C center. 

Glutamic y-semialdehyde cyclizes with a loss of H2O in a nonenzymatic process to give A i-pyrroline-5-carboxylate, which is reduced by NADPH to proline. Alternatively, the semialdehyde can be transaminated to ornithine, which is converted in several steps into arginine (Section 23.4.1). 

Arginine, via three reactions of the urea cycle, can be derived from ornithine, which is produced by transamination of glutamate semialdehyde. 

Arginine can be cleaved by arginase in the liver to form urea and ornithine. Ornithine can be transaminated to glutamate semialdehyde, which can be oxidized to glutamate. 

B. In the synthesis of these three amino acids from glucose, serine is produced from the glycolytic intermediate phosphoglyceric acid. Arginine is produced from the TCA cycle intermediate cc-ketoglutarate, and aspartate by transamination of oxaloacetate. Therefore, glyceraldehyde 3-phosphate is the only common intermediate. 

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