Proline degradation

Oxoglutarate, one of the substrates of hydroxylation, is supplied from glucose in the reaction medium via the EMP pathway and TCA cycle in E. coli and the product succinate is recycled. The mutant strain of E. coli which lacks L-proline-degrading enzyme was obtained and used for the host cells of production of L-hydroxyproline. 

GSA produced as products of ornithine and proline degradation are in the same pool in the mitochondria. 

Increased blood levels are found in the rare inborn errors, the hyperprolinaemias. The metabolic defect in type I hyper-prolinaemia is an absence of proline oxidase, the first enzyme of the proline degradative pathway. A deficiency of A -pyrroline-5-carboxylic acid dehydrogenase, another enzyme involved in proline degradation, may be responsible for type II hyper-prolinaemia. 

The incretin effect is reduced in type 2 diabetes, and this is attributed, at least in part, to reduced secretion of GLP-1. The biological actions of GLP-1 remain essentially intact in type 2 diabetes, but administration of extra GLP-1 is not a practical therapeutic option because the peptide is degraded rapidly if A < 2 min) by the enzyme dipeptidyl peptidase IV (DPP-4). DPP-4 cleaves the N-terminal dipeptide from many of the peptides that have either an alanine or a proline residue penultimate to the N-terminus (Fig. 6). 

Based on these studies, it is obvious that poly(N-acylhydroxy-proline esters) are very slowly degrading polymers. These materials may therefore be useful for long-term applications, such as implantable, multiyear contraceptive formulations. For such applications the degradation rates of poly (lactic acid)/poly (glycolic acid) devices would probably be too rapid. 

At present there is no reason evident why poly(N-acylhydroxy-proline esters) should not be suitable for the formation of microcapsules or microspheres as well. For microencapsulated drug fonmula-tions the longer degradation times of poly(N-acylhydroxyproline esters) as compared to poly (lactic acid) could again be a distinctive advantage for long-term applications. 

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. 

Hare, P.D., Cress, W.A., and Van Staden, J., Proline synthesis and degradation a model system for elucidating stress-related signal transduction, J. Exp. Bot, 50, 413,... 

The best known catabolic pathways of nitrogenous compounds are those of arginine, proline, allantoin and 4-aminobutyrate (GABA) degradation. Each of these is inducible under specific conditions, and all are subject to nitrogen-catabo-lite repression (see [7,9] and section 6.3). 

As proposed schematically in Fig. 13.2, RNI may block PHD-activity, attenuate proline hydroxylation of HIF-la, dissociate HIF-la from pVHL with the consequence of protein stabilization based on decreased proteasomal degradation. 

Plaquet et al. (PI) found in the urine of rachitic children peptides consisting of proline, hydroxyproline, and glycine, which they believed to be the products of collagen degradation. Two similar peptides containing considerable amounts of proline and hydroxyproline were isolated from the urine of a patient with rheumatoid arthritis by Mechanic et al. (Ml). One of these peptides consisted of three proline, two hydroxyproline, and nine glutamic acid residues, the second one consisted of four proline, four hydroxyproline, and one glutamic acid residues. The N-terminal amino acid in the first peptide was demonstrated to be hydroxyproline. 

Valine, leucine, and isoleucine biosynthesis Lysine biosynthesis Lysine degradation Arginine and proline metabolism Histidine metabolism Tyrosine metabolism Phenylalanine metabolism Tryptophan metabolism Phenylalanine, tyrosine, and tryptophan biosynthesis Urea cycle and metabolism of amino groups... 

Okazaki, K., Tanaka, H., Ogawa, Y. and Sagata, N. Degradation of Mos by the N-terminal proline (Pro2)-dependent ubiquitin pathway on fertilization of Xenopus eggs possible significance of natural selection for Pro2 in Mos. EMBOJ., 1993, 12, 4021-4027. 

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