Hydroxyproline, catabolism

Figure 30-11. Intermediates in i-hydroxyproline catabolism. (a-KA, a-keto acid a-AA, a-amino acid.) Numerals identify sites of metabolic defects in hyperhydroxyprolinemia and type II hyperprolinemia.

Removal of a-amino nitrogen by transamination (see Figure 28-3) is the first catabolic reaction of amino acids except in the case of proline, hydroxyproline, threonine, and lysine. The residual hydrocarbon skeleton is then degraded to amphibolic intermediates as outhned in Figure 30-1. 

L18. Lindstedt, S., and Prockop, D. J., Isotopic studies on urinary hydroxyproline as evidence for rapidly catabolized forms of collagen in the young rat. J. Biol. Chem. 236, 1399-1403 (1961). 

Uremic patients are often catabolic and exhibit a negative nitrogen balance that takes a greater protein intake to correct (K9), Moreover, amino acid losses during hemodialysis (K10) and albumin losses from peritoneal dialysis are not insignificant. There is a decrease in the body pool of albumin and other proteins (Z2). Several essential amino acids in the plasma are decreased, while some non-essential ones are increased. Tyrosineiphenylalanine and valine glycine ratios are decreased. A most common abnormality is an increase in hydroxyproline, citrul-line, and 1,3-methylhistidine. These abnormalities are corrected by hemodialysis (F14). 

In vivo, KHG aldolase catalyzes the reversible condensation of pyruvate and glyox-ylate to form KHG (Fig. 14.1-26) 166, 167. This enzyme participates in the terminal step of mammalian catabolism of L-hydroxyproline[166. The enzymes isolated and purified from bovine liver and E. coli are both type I aldolases. Limited substrate... 

In considering amino acid catabolism, one must distinguish the catabolism of the carbon chain from that of the nitrogen moiety. The breakdown of the carbon chain of the amino acids yields carbon units that can be used in carbohydrate metabolism, acetate metabolism, or the metabolism of single carbon units. The fate of the carbon units of the individual amino acids has been discussed in other sections of this book, and only a synopsis of the results will be presented here. The carbon skeletons of isoleucine, phenylalanine, threonine, tryptophan, valine, histidine, alanine, arginine, aspartic acid, glycine, proline, glutamic acid, and hydroxyproline are ultimately converted to pyruvic acid. 

In the oxidation of proline, glutamic acid is formed and in the oxidation of hydroxyproline, y-hydroxyglutamic acid is formed. Other intermediates are glutamic-y-semialdehyde and y-hydroxyglutamic-y-semi-aldehyde. These findings suggest the pattern of catabolism shown in Fig. 13. 

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