Ornithine metabolism

D-Arginine and D-ornithine metabolism D-Alanine metabolism Glutathione metabolism Alkaloid biosynthesis I Alkaloid biosynthesis II Metabolism of Complex Carbohydrates Starch and sucrose metabolism Biosynthesis and degradation of glycoprotein... 

Six patients with severe epilepsy developed stuporous encephalopathy with marked cognitive impairment when taking topiramate with valproate (5 patients) or when taking topiramate alone (1 patient). Four of the patients had hyperammonaemia which resolved when topiramate or valproate were withdrawn. The toxicity was possibly due to a synergistic effect of valproate and topiramate on liver ornithine metabolism resulting in hyperammonaemia. It was also possible that the encephalopathy was due to topiramate toxicity in at-risk patients such as those with pre-existing chronic encephalopathy. ... 

Fig. 4. Outline of synthetic and degradative pathways of arginine and proline in plant cells. This figure emphasizes the synthetic and degradative aspects of arginine and proline metabolism. Protein is considered the end-product of synthesis and the starting point of degradation. Compounds on both sides of center line are considered to be in separate pools (possibly separated by membranes). Subscript "ex refers to ornithine supplied from outside the cell. The dotted arrows indicate that,a small proportion of the ornithine metabolized goes to KAV. Abbreviations not explained in the legend to Fig. 3 are as follows AcGLU, acetylglutamic acid AcORN, acetylornithine.

Herzfeld, A., and S.M. Raper, 1976. Enzymes of ornithine metabolism in adult and developing rat intestine. Biochim. Biophys. Acta 428, 600-610. 

Matsuzawa, T., T. Kobayashi, K. Tashiro, and M. Kasahara, 1994. Changes in ornithine metabolic enzymes induced by dietary-protein in small-intestine and liver-intestine-liver relationship in ornithine supply to liver. J. Biochem. 116,721-727. 

Riby, J.E., R.E. Hrrrwitz, and N. Kretchmer, 1990. Development of ornithine metabolism in the mouse intestine. 

A -Pyrroline has been prepared in low yield by oxidation of proline with sodium hypochlorite (71), persulfate (102), and periodate (103). A -Pyrroline and A -piperideine are products of enzymic oxidation via deamination of putrescine and cadaverine or ornithine and lysine, respectively (104,105). This process plays an important part in metabolism and in the biosynthesis of various heterocyclic compounds, especially of alkaloids. 

Certain amino acids and their derivatives, although not found in proteins, nonetheless are biochemically important. A few of the more notable examples are shown in Figure 4.5. y-Aminobutyric acid, or GABA, is produced by the decarboxylation of glutamic acid and is a potent neurotransmitter. Histamine, which is synthesized by decarboxylation of histidine, and serotonin, which is derived from tryptophan, similarly function as neurotransmitters and regulators. /3-Alanine is found in nature in the peptides carnosine and anserine and is a component of pantothenic acid (a vitamin), which is a part of coenzyme A. Epinephrine (also known as adrenaline), derived from tyrosine, is an important hormone. Penicillamine is a constituent of the penicillin antibiotics. Ornithine, betaine, homocysteine, and homoserine are important metabolic intermediates. Citrulline is the immediate precursor of arginine. 

L-Ornithine transcarbamoylase catalyzes transfer of the carbamoyl group of carbamoyl phosphate to ornithine, forming citrulline and orthophosphate (reaction 2, Figure 29-9). While the reaction occurs in the mitochondrial matrix, both the formation of ornithine and the subsequent metabolism of citmlline take place in the cytosol. Entry of ornithine into mitochondria... 

There are numerous abnormalities of cysteine metabolism. Cystine, lysine, arginine, and ornithine are excreted in cystine-lysinuria (cystinuria), a defect in renal reabsorption. Apart from cystine calculi, cystinuria is benign. The mixed disulfide of L-cysteine and L-homocysteine (Figure 30-9) excreted by cystinuric patients is more soluble than cystine and reduces formation of cystine calculi. Several metabolic defects result in vitamin Bg-responsive or -unresponsive ho-mocystinurias. Defective carrier-mediated transport of cystine results in cystinosis (cystine storage disease) with deposition of cystine crystals in tissues and early mortality from acute renal failure. Despite... 

Figure 31-3. Arginine, ornithine, and proline metabolism. Reactions with solid arrows all occur in mammalian tissues. Putrescine and spermine synthesis occurs in both mammals and bacteria. Arginine phosphate of invertebrate muscle functions as a phosphagen analogous to creatine phosphate of mammalian muscle (see Figure 31-6).

Yudkoff, M., Daikhin,Y., Nissim, I., Jawad,A.,Wilson, J. and Batshaw, M. B. In vivo nitrogen metabolism in ornithine transcarbamylase deficiency. /. Clin. Invest. 98 2167-2173, 1996. 

Ye, X., Robinson, M. B., Batshaw, M. L., Furth, E. E., Smith, I. and Wilson, J. M. Prolonged metabolic correction in adult ornithine transcarbamylase-deficient mice with adenoviral vectors. / Biol. Chem. 271 3639-3646,1996. 

Hippuric acid is a normal product of metabolism. It is produced in the kidney by the enzymic union of benzoic acid and glycine (Schmiede-berg and Bunge, 1877). In birds benzoic acid is rendered innocuous by combination with ornithine (aS-diamino-valeric acid) to form the dibenzoyl-derivative, so-called ornithuric acid (Jaffe). 

In the next 2 to 3 years further experiments, particularly by Eggleston, who had joined Krebs in January 1936, confirmed and extended the observations. Careful quantitative evaluation of the data indicated that citrate like fumarate (Szent-Gyorgi) and like ornithine in the urea cycle exerted a catalytic effect on muscle metabolism. If arsenite, which blocks 2-oxoglutarate oxidation, was added with citrate to a respiring pigeon-muscle preparation, 2-oxoglutarate accumulated. 

Kestens, P.J. (1964). La Perfusion du Foie Isole. Editions Arscia S.A. Bruxelles. Meyer, AJ. Lamers, W.H., Chamulead, R.A.F.M. (1990). Nitrogen metabolism and ornithine cycle fixation. Physiol. Rev. 70, 701-748. 

Ammonia is generated mainly from the metabolism of amino acids and from the catabolism of purine and pyrimidine bases, which are produced from nucleic acids. Since it is toxic, it must be converted to a non-toxic compound for excretion from the body. This is achieved via the ornithine cycle, more usually known as the urea cycle. 

Research is currently directed towards a better understanding of the metabolic alterations of cancer patients, the definition of nutritional regimens that can efficiently support the host without promoting tumour growth, and on the impact of nutritional pharmacology on the host-tumour relationship. Glutamine, arginine, ornithine-... 

Ornithine is a metabolically quite active amino acid, and the important precursor of pyrrolidine nucleus, which is found in pyrrolizidine alkaloids. Ornithine itself is a non-protein amino acid formed mainly from L-glumate in plants, and synthesized from the urea cycle in animals as a result of the reaction catalyzed by enzymes in arginine. 

Among the numerous enzymes that utilize pyridoxal phosphate (PLP) as cofactor, the amino acid racemases, amino acid decarboxylases (e.g., aromatic amino acids, ornithine, glutamic acid), aminotransferases (y-aminobutyrate transaminase), and a-oxamine synthases, have been the main targets in the search for fluorinated mechanism-based inhibitors. Pharmaceutical companies have played a very active role in this promising research (control of the metabolism of amino acids and neuroamines is very important at the physiological level). 

Metabolism of polyamines has a direct action on cell proliferation. Thus, it is a therapeutic target for the design of antitumor agents. However, inhibition of ornithine decarboxylase (ODC) by specific inhibitors does not completely cancel the activity. This is due to the existence of other biosynthetic pathways (i.e., SAM-DC). These pathways are themselves regulated by polyamines. 

---