Regeneration Urea cycle

Fig. 6.14. Biosynthesis of NO. The starting point of NO synthesis is arginine. Arginine is converted by NO synthase, together with O, and NAD PH, to NO and citruUine. Arginine can be regenerated from citrulline via reactions of the urea cycle.

However, the urea cycle also causes a net conversion of oxaloacetate to fumarate (via aspartate), and the regeneration of oxaloacetate (Fig. 18-12) produces NADH in the malate dehydrogenase reaction. Each NADH molecule can generate up to 2.5 ATP during mitochondrial... 

Ammonia is highly toxic to animal tissues. In the urea cycle, ornithine combines with ammonia, in the form of carbamoyl phosphate, to form citrulline. A second amino group is transferred to citrulline from aspartate to form arginine—the immediate precursor of urea. Arginase catalyzes hydrolysis of arginine to urea and ornithine thus ornithine is regenerated in each turn of the cycle. 

Formation of citrulline Ornithine and citrulline are basic amino acids that participate in the urea cycle. [Note They are not incorporated into cellular proteins, because there are no codons for these amino acids (see p. 429).] Ornithine is regenerated with each turn of the urea cycle, much in the same way that oxaloacetate is regenerated by the reactions of the citric acid cycle (see p 109). The release of the high-energy phosphateof carbamoyl phosphate as inorganic phosphate drives the reaction in the forward direction. The reaction product, citrulline, is trans ported to the cytosol. 

In the urea cycle ammonia is first combined with C02 to form carbamoyl phosphate. This then combines with ornithine to form citrulline. Citrulline then condenses with aspartate, the source of the second nitrogen atom in urea, to form argininosuccinate. This compound is in turn split to arginine and fumarate, and the arginine then splits to form urea and regenerate ornithine The first two reactions take place in the mitochondria of liver cells, the remaining three in the cytosol. 

The other part of the urea cycle that has occurred is the conversion of the carbons of aspartate to fumarate. The fumarate is recycled back to oxaloacetate through TCA cycle reactions in the mitochondrion. Transamination with glutamate regenerates aspartate. The glutamate comes from the glutamate dehydrogenase reaction. 

The final step of the urea cycle is the cleavage of arginine to release urea and regenerate ornithine. Ornithine then reenters the mitochondria via the ORNT-1 ornithine-citrulline antiporter. ARG-1 is a cytosolic homotrimeric enzyme of 35-kd monomers that is expressed in fiver and red blood cells. A second mitochondrial arginase (ARG-2) most likely plays a role in nitric oxide synthesis and is most abundant in brain, kidney, and prostate. ARG-1 deficiency is unique among the urea cycle deficiencies as patients do not present with hyperammonemia and encephalopathy but rather develop progressive spasticity of the lower limbs. Biochem-... 

FIGURE 8.11 The urea cycle. The urea cycle is based on the ornithine molecule. Ornithine acts as a chemical scaffold, on which a moiety of urea is built- Ibe finished moiety of urea is discharged by hydrolysis, prtKluctng free urea and regenerating the original molecule of ornithine. 

Ornithine An a-amino acid similar in structure to lysine but having one methylene group less in the side chain. It is carbamoylated to form cit-rulline to begin the urea cycle and is regenerated in the final step that releases urea. 

NO is formed enzymatically from arginine with the help of NO synthase, producing citrulline (Fig. 6.18). Citrulline and arginine are intermediates of the urea cycle, and arginine can be regenerated from citrulline by urea cycle enzymes. 

The term Krebs bicycle refers to two interlocking cyclic reaction pathways. The aspartate-arginosuccinate shunt of the citric acid cycle is responsible for regenerating the aspartate needed for the urea cycle from fumarate. The molecule that the two cycles have in common is arginosuccinate. 

Ornithine is an amino acid. However, it is not incorporated into proteins during the process of protein synthesis because no genetic codon exists for this amino acid. Although ornithine is normally regenerated by the urea cycle (one of the products of the arginase reaction), ornithine also can be synthesized de novo if needed. The reaction is an unusual transamination reaction catalyzed by ornithine aminotransferase under specific conditions in the intestine (Fig. 38.14). The usual direction of this reaction is the formation of glutamate semialdehyde, which is the first step of the degradation pathway for ornithine. 

The Krebs cycle completes the disassembly of glucose to six molecules of CO2 by combining the two carbon atoms from acetyl-CoA with oxaloacetate to make citrate this is then successively transformed to release two molecules of CO2 and to regenerate oxaloacetate. This reformation of a carrier molecule in a cyclic manner led Hans Krebs to the concept of a metabolic cycle, he first observed this with the urea cycle (Sec. 14.8). 

F7 Fausto, N., Brandt, J. T. and Kesner, L. Possible interactions between the urea cycle and synthesis of pyrimidines and polyamines in regenerating liver. Cancer Res., 35, 397-404 (1975)... 

Two different arginase (ARG) isoforms, with different biochemical characteristics and tissue distribution, have been identified (Reddi etal, 1975). These enzymes were shown to be the product of two different, but related genes (see Cederbaum et al, 2004). ARG I (liver type) is cytosolic and the last step of the urea cycle which regenerates ornithine and releases urea. In contrast, ARG II (kidney type) is present in the mitochondria and is involved in providing ornithine for poly amine and prohne synthesis (Cederbaum et al, 2004) and in regulating arginine availability for nitric oxide synthesis (Topal et al, 2006). ARG II is present in enterocytes and thus has the potential to generate ornithine... 

In the final step, isourea is released from the guanidinium group of the arginine by hydrolysis (not shown), and is immediately rearranged into urea. In addition, ornithine is regenerated and returns via the ornithine transporter into the mitochondria, where it becomes available for the cycle once again. 

In the synthesis of carbamates, R NH.C02R, from A iV -dialkylureas, (R NH)2CO, and dialkyl carbonates, (RO)2CO, dibutyltin oxide, Bu2SnO, acted as an efficient catalyst. The proposed mechanism (Scheme 13) involves addition of the dialkyl carbonate to Bu2SnO to give an adduct (43), which is attacked by the urea to yield a new tin complex (44) and one molecule of carbamate. Attack by dialkyl carbonate upon this complex (44) yields a further molecule of carbamate and regenerates the original tin complex (43), which can continue the catalytic cycle.42... 

The simultaneous decomposition of pentachlorophenol and regeneration of activated carbon, using microwaves was reported [46], claiming that the quality of the carbon was maintained or actually increased after several adsorption/microwave-regeneration cycles. Carbon, in graphite form, has also been used as a microwave absorbent for the microwave pyrolysis of urea [47]. 

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