Proline ornithine

C. S5mthesis and Catabolism of Proline, Ornithine, Arginine, and Polyamines... 

The 5-carbon skeleton of glutamic acid gives rise directly to those of proline, ornithine, and arginine. The reactions are outlined in Fig. 24-9. Arginine, in turn, is involved in the urea cycle, which is shown in detail in Fig. 24-10. Arginine is also a biosynthetic precursor of the polyamines. Another important biosynthetic product of glutamate metabolism is 8-aminolevulinate, a precursor to porphyrins (Eq. 24-44) in some organisms.139... 

Experiments (although subject to some criticism) carried out by Klein and Linser (57) would indicate that stachydrine formation in the plant is markedly increased by injection into the hollow stalks of the possible precursor of the betaine. On the assumption that stachydrine could result from simple methylation of proline which in turn might be derived from glutamic acid via pyrrolidonecarboxylic acid, or from arginine via ornithine, injections were made of 1-2 % solutions of proline, ornithine dihydrochloride and sodium glutamate. The experiments carried out on Stachys palustris L., Stachys recta L., and Galeopsis ochroleuca Lam. revealed an apparent increase in stachydrine content as a result of these injections. 

T. a. for therapeutic purposes are derived almost entirely from plant sources. The tropane ring is derived biosynthetically from compounds of the glutamic acid/proline/ornithine group, via an iV-methylpyrro-line cation which condenses with acetoacetic acid to form ketones (of the tropinone type). Following reduction of the ketone function, the resulting amino alcohol becomes esterified with an appropriate aromatic acid (ecgonine is esterified with benzoic acid, with additional methylation of the 2-carboxyl function to form cocaine tropine is esterified with tropic acid to form hyoscyamine, which can be further epox-idized to scopolamine). See Fig. 2. 

Fig. 217. Biosynthesis and transformation of the amino acids of the glutamic acid-proline-ornithine family...

The interrelationships between proline, ornithine, and glutamic acid are discussed further in the chapter Synthetic Processes Involving Amino Acids. 

Three of the amino acids, alanine, aspartic acid, and glutamic acid are readily formed by transamination from products of the citric acid cycle. This has been explained in the chapter. Carbon Catabolism of Amino Acids. Glutamic acid is the probable precursor of a considerable number of the other nonessential amino acids, namely, proline, hydroxy-proline, ornithine, and from it arginine. 

As a redox couple, proline and pyrroline-5-carboxylate provide a mechanism for the intercompartmental and intercellular transfer of redox potential. The transfer of redox potential alters the ratio of NADP /NADPH thereby activating certain metabolic pathways. Although the reduction of pyrroline-5-carboxylate is the central mechanism in the transfer of redox potential, the metabolic interconversions of proline, ornithine, and glutamate with pyrroline-5-carboxylate as the obligate intermediate also may play a role. The endpoint of this regulation appears to be the formation of purine ribonucleotides by both salvage and de novo mechanisms. Proline and pyrroline-5-carboxylate appear to be metabolic signals which can be fine-tuned by humoral factors to coordinate the metabolism of amino acids and ribonucleotides. When the transfer is from cell to cell, proline and pyrroline-5-carboxyl-ate can function as intercellular communicators. 

Fig. 2. Metabolic scheme for the interconversions of proline, ornithine and glutamate. Enzymes catalyzing the reactions are designated by the following numbers (1) P5C synthase (2) P5C dehydrogenase (3) ornithine aminotransferase (4) P5C reductase (5) proline oxidase, Step 6 is spontaneous. Adapted from ref. (85).

B. Theoretical Redox Transfers Mediated by the Interconversions of Proline, Ornithine, and Glutamate... 

Based on the general hypothesis—the interconversions of proline, ornithine and glutamate regulate the NADF " - NADPH redox state — one can reexamine the diverse regulatory mechanisms regulating this enzyme system relative to a metabolic endpoint other than the exchange... 

In these studies the proline-P5C interconversions as central to redox exchange have been emphasized. But hydroxyproline and 3-OH-P5C, the degradative product of hydroxyproline, also may produce regulatory effects, at least theoretically. Since 3-OH-P5C derives only from the degradation of hydroxyproline (1-3), direct effects mediated by their interconversions seem unlikely. However, 3-OH-P5C can interact with the proline - ornithine - glutamate system at several steps (35, 102). Such an interaction is of considerable interest since the intake of hydroxyproline, an animal product, can be nutritionally controlled. Even the endogenous release of hydroxyproline from the breakdown of connective tissue and bone collagen may depend, at least in part, on nutritional factors such as calcium and vitamin D. 

P5C transfers redox potential as metabolic information. And as a transducing mechanism, the metabolism of proline-P5C can be acted upon by more specific humoral regulators. With the production of ribonucleotides as an endpoint, this mechanism coordinates the metabolism of amino acids and ribonucleotides. Indeed, much needs to be done to prove these hypotheses and to fully explore their implications. But the work summarized here leads to proposals that can serve as a new conceptual framework for regulatory mechanisms mediated by proline, ornithine, and glutamate. 

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