Ornithine reactions

Figure 29-9. Reactions and intermediates of urea biosynthesis. The nitrogen-containing groups that contribute to the formation of urea are shaded. Reactions and occur in the matrix of iiver mitochondria and reactions , , and in iiver cytosoi. COj (as bicarbonate), ammonium ion, ornithine, and cit-ruiiine enter the mitochondriai matrix via specific carriers (see heavy dots) present in the inner membrane of iiver mitochondria.

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... 

Hyperammonemia Type 2. A deficiency of ornithine transcarbamoylase (reaction 2, Figure 29-9) produces this X chromosome-linked deficiency. The mothers also exhibit hyperammonemia and an aversion to high-protein foods. Levels of glutamine are elevated in blood, cerebrospinal fluid, and urine, probably due to enhanced glutamine synthesis in response to elevated levels of tissue ammonia. 

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).

Diethylenetriaminepentaacetic acid DFMO al-Difluoromethyl ornithine DFP Diisopropyl fluorophosphate DFX Desferrioxamine DGLA Dihomo-y-linolenic acid DH Delayed hypersensitivity DHA Docosahexaenoic acid DHBA Dihydroxybenzoic acid DHR Delayed hypersensitivity reaction... 

Also N, N -bisprotected pyrazole-l-carboxamidines are applied for preparation of guanidines.[91,[9al A variation of this reaction permitted the copper salt of ornithine to be converted to the copper salt of arginine [10]... 

The glutamic moiety of TNP-351, a pyrrolo[2,3-d]pyrimidine glutamic acid derivative, and related compounds have been transformed into their A-co-masked ornithine analogs which show remarkable antifolate activity <00CPB1270>. The reaction of the heterocyclic enamine 77 with tosyl azide leads to the tosylimino derivative of 1,2,4-triazolo[l, 5-a]pyrimidine 79. Extrusion of nitrogen from the primary adduct 78 is followed by a 1,2-shift of a methyl group to yield 79 <00JHC195>. 

Carbamyl phosphate condenses with ornithine to yield citrulline in the ornithine transcarbamylase (OTC) reaction. OTC is encoded on band p21.1 of the X chromosome, where the gene contains 8 exons and spans 85 kb of DNA. The activity of this enzyme is directly related to dietary protein. There may be tunneling of ornithine transported from the cytosol to OTC, with the availability of intramitochondrial ornithine serving to regulate the reaction. 

Argininosuccinate lyase (AL) (Fig. 40-5 reaction 4) cleaves argininosuccinate to form fumarate, which is oxidized in the tricarboxylic acid cycle, and arginine, which is hydrolyzed to urea and ornithine via hepatic arginase. Both AL and arginase are induced by starvation, dibutyryl cyclic-AMP and corticosteroids. 

The paper by Krebs and Henseleit (1932), Experiments on the Formation of Urea in Animal Bodies (Klinische Wochenschrift 11,759), contained the phrases... in the synthesis of urea in the living cell, ornithine acts like a catalyst. We therefore draw the conclusion. .. that the primary reaction for the synthesis of urea from ammonia is... 

Cohen and Grisolia then concentrated on the first step in the reaction, obtaining citrulline from ornithine. The reaction appeared to depend on oxygen, a requirement traced to the need for high concentrations of ATP. Physiologically the formation of urea occurs at very low levels of ammonia, which is extremely toxic as it is also lipid soluble and enters cells very easily. Cells are not very effectively buffered against OH. ... 

Some studies document hydrolysis of an arginine residue to ornithine and/or citrulline [87], The reactions are insufficiently understood, but an attractive hypothesis is that they involve the hydrolysis of the imine bond of the guanidino group (see also Sect. 11.6). 

Examples of this reaction are provided by the hexapeptide [Arg6,D-Trp7,9,MePhe8]substance P-(6-ll) (6.52, Fig. 6.17) and the two model tripeptides Phe-Trp-Arg-NH2 and Phe-Trp-Arg (6.51, R=NH2 and OH, respectively) [76b], Under alkaline conditions, all three compounds formed the ornithine analogue as an important product (Fig. 6.17, Reactions c), irrespective of whether arginine was at the N-terminus (6.52) or the C-ter-minus (6.51). In contrast, the model tripeptides Arg-Trp-Phe-NH2 and Arg-Trp-Phe (6.50, R=NH2 and OH, respectively), which also have arginine at the N-terminus, did not yield ornithine. This discrepancy was ascribed to steric differences, as the tripeptides contain L-Trp and the hexapeptide contains D-Trp. 

On an average Western diet, adnlt hnmans excrete around 30 g of nrea per day but this can easily triple on a protein-rich diet. The reactions and the concept of a cycle were discovered by Krebs Henseleit (1932). Snbseqnent work clari-hed the details of what has become known as the ornithine or the nrea cycle. 

From Pseudomonas mendocina five siderophores were isolated by chromatography. They are reported to have identical molecular masses of 1,152 Da (the also reported 3a) value of 929 Da is an error L. E. Hersman, private communication) and an identical amino acid composition, which has not been revealed 141a). Color reactions show the presence of a hydroxamate, but not of a catecholate grouping. A gene analysis suggests a partial sequence acyl-Asp-Dab-Ser-formylOHOm-Ser-formylOHOm where asparagine could be OHAsp and the C-terminal ornithine cOHOm 9b). In which way the five isomeric siderophores with identical molecular masses differ from each other is not clear. 

This enzyme [EC 3.5.1.16], also known as acetylornithi-nase and A -acetylornithinase, catalyzes the reaction of water with A -acetylornithine to produce acetate and ornithine. The enzyme also catalyzes the hydrolysis of A -acetylmethionine. 

This enzyme [EC 3.5.3.12], also known as agmatine imi-nohydrolase, catalyzes the hydrolysis of agmatine to produce A/ -carbamoylputrescine and ammonia. The plant enzyme also catalyzes the reactions of EC 2.1.3.3 (ornithine carbamoyltransferase), EC 2.1.3.6 (putrescine car-bamoyltransferase) and EC 2.122 (carbamate kinase), thereby functioning as a putrescine synthase, converting agmatine and ornithine into putrescine and citrulline, respectively. 

This enzyme catalyzes the reaction of an w-amino acid with pyruvate to produce L-alanine and an aldehyde-containing carboxyhc acid. See Lysine 6-Aminotransferase Ornithine Aminotransferase... 

This enzyme [EC 1.5.1.24], also referred to as A -(1-l-carboxyethyl)-L-ornithine NADP+ oxidoreductase, reversibly catalyzes the reaction of ornithine with pyruvate and NADPH to produce A -(l-carboxyethyl)ornithine, NADP+, and water. Lysine can also serve as a substrate, acting on A , albeit not as effectively as ornithine. 

This enzyme [EC 2.3.1.35], also known as ornithine ace-tyltransferase, and ornithine transacetylase, catalyzes the reversible reaction of A -acetyl-L-ornithine with L-gluta-mate to produce L-ornithine and A-acetyl-L-glutamate. This protein also exhibits a low hydrolysis activity (about 1% of that of the transferase activity) of iV -acetyl-L-ornithine to yield acetate and L-ornithine. This enzyme is not identical with A-acetylglutamate synthase [EC 2.3.1.1]. 

This enzyme [EC 2.1.4.1], also known as L-arginine gly-cine amidinotransferase, catalyzes the reaction of L-argi-nine with glycine to produce L-ornithine and guanidi-noacetate. Canavanine can serve as the substrate instead of arginine. 

This enzyme [EC 2.1.4.2] catalyzes the reaction of arginine with l-amino-l-deoxy-xcyZ/o-inositol 4-phosphate to produce ornithine and l-guanidino-l-deoxy-scy//o-inositol 4-phosphate. Other substrates include lo-l-gua-nidino-3-amino-l,3-dideoxy-xcy//o-inositol 6-phosphate, streptamine phosphate and 2-deoxystreptamine phosphate. Canavanine can substitute for arginine. 

This enzyme [EC 1.5.1.19], also known as D-nopaline synthase, catalyzes the reaction of Al -(D-l,3-dicarboxy-propyl)-L-arginme with NADP+ and water to produce L-arginine, NADPH, and a-ketoglutarate (or, 2-oxoglu-tarate). In the reverse direction, the enzyme catalyzes the formation of D-nopaline from L-arginine as well as D-ornaline from L-ornithine. 

This enzyme [EC 1.5.1.11], also known as D-octopine synthase, catalyzes the reversible reaction of A -(d-1-carboxyethyl)-L-arginine with NAD+ and water to produce L-arginine, pyruvate, and NADH. The enzyme, in the reverse direction, will also act on L-ornithine, L-ly-sine, and L-histidine. 

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