Biosynthesis Of Urea

Urea biosynthesis occurs in four stages: (1) transamination, (2) oxidative deamination of glutamate, (3) ammonia transport, and (4) reactions of the urea cycle (Figure 29-2).

Transamination Transfers a-Amino Nitrogen to a-Ketoglutarate, Forming Glutamate

Transamination interconverts pairs of a-amino acids and a-keto acids (Figure 29-3). All the protein amino acids except lysine, threonine, proline, and hydroxypro-line participate in transamination. Transamination is readily reversible, and aminotransferases also function in amino acid biosynthesis. The coenzyme pyridoxal phosphate (PLP) is present at the catalytic site of aminotransferases and of many other enzymes that act on amino acids. PLP, a derivative of vitamin Bg, forms an enzyme-bound Schiff base intermediate that can rearrange in various ways. During transamination, bound PLP serves as a carrier of amino groups. Rearrangement forms an a-keto acid and enzyme-bound pyridoxamine phosphate, which forms a Schiff base with a second keto acid. Following removal of a-amino nitrogen by transamination, the remaining carbon "skeleton" is degraded by pathways discussed in Chapter 30.

Alanine-pyruvate aminotransferase (alanine amino-transferase) and glutamate-a-ketoglutarate aminotrans-ferase (glutamate aminotransferase) catalyze the transfer a-Amino acid a-Amino acid a-Keto acid a-Ketoglutarate L-Glutamate

a-Ketoglutarate L-Glutamate

UREA CYCLE

UREA CYCLE

Urea

Urea

Figure 29-2. Overall flow of nitrogen in amino acid catabolism.

fvch-co-

II O

Figure 29-3. Transamination. The reaction is freely reversible with an equilibrium constant close to unity.

of amino groups to pyruvate (forming alanine) or to a-ketoglutarate (forming glutamate) (Figure 29-4). Each aminotransferase is specific for one pair of substrates but nonspecific for the other pair. Since alanine is also a substrate for glutamate aminotransferase, all the amino nitrogen from amino acids that undergo transamination can be concentrated in glutamate. This is important because L-glutamate is the only amino acid that undergoes oxidative deamination at an appreciable rate in mammalian tissues. The formation of ammonia from a-amino groups thus occurs mainly via the a-amino nitrogen of L-glutamate.

Transamination is not restricted to a-amino groups. The 5-amino group of ornithine—but not the e-amino group of lysine—readily undergoes transamination. Serum levels of aminotransferases are elevated in some disease states (see Figure 7-11).

l-glutamate dehydrogenase

Diabetes 2

Diabetes 2

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