Carbamyl phosphate kinase

Acetate kinase is phosphorylated by acetyl phosphate and it has been shown that the phosphoenzyme can synthesise ATP from ADP, and acetyl phosphate from acetate. The mode of decomposition of carbamyl phosphate in aqueous solution is pH dependent and can proceed with either the production of ammonia and carbon dioxide (equation 1), or cyanate (equation 2). No cyanate could be detected during the hydrolysis... 

Animal and bacterial enzymes that utilize or synthesize carbamyl phosphate have activity with acetyl phosphate. Acyl phosphatase hydrolyzes both substrates, and maybe involved in the specific dynamic action of proteins. Ornithine and aspartic transcarbamylases also synthesize acetylornithine and acetyl aspartate. Finally, bacterial carbamate kinase and animal carbamyl phosphate synthetase utilize acetyl phosphate as well as carbamyl phosphate in the synthesis of adenosine triphosphate. The synthesis of acetyl phosphate and of formyl phosphate by carbamyl phosphate synthetases is described. The mechanism of carbon dioxide activation by animal carbamyl phosphate synthetase is reviewed on the basis of the findings concerning acetate and formate activation. 

Stadtman has demonstrated (42) the conversion of carbamyl phosphate and acetate to acetyl phosphate, catalyzed either by a crude lysine system or by a purified acetate kinase from C. sticklandii. ADP and... 

The first step in the formation of urea from ammonia is its combination with bicarbonate to form carbamyl phosphate (Fig. 1). This contributes only one nitrogen atom to urea, the other being donated by aspartic acid in the third step of the pathway. A -Acetylglutamate is required as cofactor, and the presence of Mg is essential, ATP being converted to ADP in the process. The reaction is catalyzed by carbamyl phosphate synthetase (carbamate kinase EC 2.7.2.2). It has been shown that there are probably two forms of this enzyme, at least in rat liver. One is ammonia dependent, is primarily associated with mitochondria, and may be the enzyme responsible for the formation of carbamyl phosphate in the synthesis of urea. The other, which is glutamine dependent, is probably mainly extramitochondrial and may supply the carbamyl phosphate used... 

AcK acetate kinase AcP acetyl phosphate AdK adenylate kinase AP A p ,pn-di(adenosine 5 -) n-phosphate ARS aminoacyl tRNA synthetase ATP, ADP, AMP adenosine 5 -tri-, di-, monophosphate ATP-u-S (Sp)-adenosine 5 -0-(l-thiotriphos-phate), ATP-y-S adenosine 5 -0-(3-thiotriphosphate) CK carbamyl kinase CP carbamyl phosphate CrK creatine kinase CTP, CDP, CMP cytidine 5 -tri-, di-, monophosphate dATP, dAMP deoxyadenosine 5 -tri-, monophosphate DNA deoxyribonucleic acid AG change in free energy GK glycerol kinase GTP, GDP, GMP guanosine 5 -tri-, di-, monophosphate HK hexokinase IUB International Union of Biochemistry MCP methoxycarbonyl phosphate NTP, NDP, NMP nucleoside 5 -tri-, di-, monophosphate PC phosphocreatine PEP phosphoenol pyruvate P orthophosphate PK pyruvate kinase P polyphosphate PnK poly-... 

The overall capacity of pyrimidine nucleotide de novo synthesis appears to be higher in rat liver than in rat brain. This can also be concluded from the higher activities of carbamyl phosphate synthetase II and aspartate transcarbamylase in liver (2,4). The liver primarily depends on the de novo pathway for nucleotide synthesis. With liver slices pyrimidine nucleotides are predominantly derived from OA uridine is mainly catabolyzed to uracil and 3-alanine (16) in agreement with high activity of uridine phosphorylase. With brain slices uridine was superior to CO2 or OA in labelling RNA (8). This concords with the relatively high activity of uridine kinase. In vivo, however, cytidine appears to be a more important substrate for nucleotide synthesis (17), since uridine in predominantly catabolyzed by various tissues, including liver. 

Citrullinase. The bacterial enzyme that degrades citrulline has been called citrullinase, citrulline ureidase and citrulline phosphorylase. The reaction requires inorganic phosphate, Mg++, and ADP, and ATP is formed together with NH3, CO2, and ornithine. Arsenate supports the breakdown of citrulline in the absence of phosphate and adenine nucleotides. The mechanism of the phosphorolysis was shown by Jones et to be straightforward the first products are ornithine and carbamyl phosphate, which had previously been considered to be too unstable to exist free. Carbamyl phosphate transfers its phosphate to ADP in a reversible kinase reaction, and the carbamyl group also can react with ornithine to form citrulline (VI). These reversible reactions explain the requirement for stoichiometric amounts of adenine nucleotides for a coupled reaction to remove the labile phosphate. Carbamic acid may equilibrate non-... 

This reaction occurs spontaneously and is accelerated by anions and by certain nitrogenous bases. Nevertheless, the nonenzymatic hydration of CO2 and the dehydration of carbonic acid are very slow compared with the reactions that require or produce one of these forms, and carbonic anhydrase is found in many tissues, where it performs essential physiological functions. Its presence in red cells is associated with the necessity of transferring CO2 efficiently both in the removal of CO2 from body tissues and in the elimination of CO2 in lungs or gills. This activity has also been found in secretory cells and in green plants, but its function in these places is not established. The formation of carbamic acid from CO2 and ammonia and the subsequent formation of carbamyl phosphate by the kinase are greatly accelerated by the presence of carbonic anhydrase. 

Because carbamate is considered to be involved, the term carbamate kinase may be used for this enzyme. The reaction is freely reversible which indicates that the free energy of hydrolysis of carbamyl phosphate and ATP are of the same order of magnitude. 

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