Carbamyl phosphate

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... 

Reactions involving carbamyl phosphate in the degradation of arginine in Clostridia, and the fermentation of allantoin by Streptococcus allantoicus... 

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. 

Urinary orotic acid generally is very elevated in babies with OTC deficiency and normal or even low in the infant with CPS deficiency. Patients with OTC deficiency have orotic aciduria because carbamyl phosphate spills into the cytoplasm, where it enters the pathway of pyrimidine synthesis. 

Diagnosis of CPS or OTC deficiency may not be apparent from the blood aminogram. Ornithine levels typically are normal. The presence of hyperammonemia, hyperglu-taminemia, hyperalaninemia and orotic aciduria in a critically ill infant affords presumptive evidence for OTC deficiency. The presence of this blood aminogram without orotic aciduria suggests carbamyl phosphate synthetase deficiency. 

Carbamyl phosphate synthetase deficiency. Carbamyl phosphate synthetase deficiency is rare. Neonates quickly develop lethargy, hypothermia, vomiting and irritability. The hyperammonemia typically is severe, even exceeding 1 mmol/1. Occasional patients with a partial enzyme deficiency have had a relapsing syndrome of lethargy and irritability upon exposure to protein. Brain damage can occur in both neonatal and late-onset groups. 

The underlying biochemical defect is a failure of mitochondrial uptake of ornithine. This results in a failure of citrulline synthesis and a consequent hyperammonemia. Urinary orotic acid is high, presumably because of underutilization of carbamyl phosphate. In contrast, excretion of creatine is low, reflecting the inhibition of glycine trans-amidinase by excessive levels of ornithine. 

CPS carbamyl phosphate synthetase FSH follicle-stimulating hormone... 

Fig. 7. A pictorial representation of two views of the structure of aspartate transcarbamyl-ase. The hatched portions are regulatory subunits and the white portions are catalytic subunits. The binding sites for CTP ( ), carbamyl phosphate (O), and aspartate ( ) are indicated along with an SH group that is near the active site and a Zn atom that is required for the binding between regulatory and catalytic subunits.

Carbamyl phosphate synthase deficiency p Glnt, Citt, Alat, Lyst... 

Davis, R.H. Carbamyl phosphate synthesis in Neurospora crassa. I. Preliminary characterization of arginine-specific carbamyl phosphokinase. Biochim. Biophys. Acta, 107, 44-53 (1965)... 

The affinities of the transport protein for the nucleoside triphosphates ITP and GTP and the corresponding diphosphates deduced from the concentration dependence of either calcium-dependent phosphate liberation or phosphate incorporation during calcium efflux are at least 10 to 400 times lower than the affinity of the adenine nucleotides (Fig. 12). The affinities for acetyl phosphate, carbamyl phosphate, para-nitro-... 

Precursors for the biosynthesis of biodn include pimelic acid, cysieinc, and carbamyl phosphate. Desthiobiotin acts as an intermediate. In plants, the production sites are seedlings and leaves In most animals, production is in the intestine. Storage site is the liver... 

Ovalbumin Conalbumin Ovomucoid Lysozyme Vitellogenin apo-VLDL Glucose-6-P-dehydrogenase Oviduct Oviduct (liver) Oviduct Oviduct Liver Liver Uterus Thyroid Hormones Carbamyl phosphate synthase Growth hormone Prolactin ( ) a-Glycerophosphate dehydrogenase Malic enzyme Liver Pituitary Pituitary Liver (mitochondria) Liver... 

This is an allosteric enzyme that requires zinc for structural stability. It catalyzes the condensation of carbamyl phosphate with L-aspartate to give carbamyl-L-aspartate and phosphate (equation... 

Hyperammonemia has occurred during parenteral nutrition as a component of therapy for renal insufficiency (905). The hyperammonemia presented as a change in mental status, developing about 3 weeks after initiation of parenteral nutrition therapy in most cases the episodes are of increasing duration and paroxysmal. In three of the patients, serum amino acid analysis in the acute phase showed reduced concentrations of ornithine and citrulline (the respective substrate and product of condensation with carbamyl phosphate at its entry into the urea cycle). Concentrations of arginine, the precursor to ornithine, were raised. 

Carbamyl phosphate synthetase catalyzes the synthesis of carbamyl-P from HCO3-, glutamine, and 2 moles of ATP. The enzyme also catalyzes the HC03 -dependent hydrolysis of ATP. Raushel and Villafranca (5) followed the exchange of from the bridge to the nonbridge position of [y- 0]ATP after Incubation with enzyme and bicarbonate. The exchange rate was O.A times the rate of ADP formation. These results support the formation of carboxy phosphate as the first Intermediate In the catalytic sequence. 

The positional Isotope exchange has also been measured with 31p-nmr In the reverse reaction of carbamyl phosphate synthetase ... 

Carbamyl phosphate was synthesized with In all oxygens except the carbonyl oxygen of carbon. The exchange of the bridge oxygen Into the carbonyl oxygen was followed by nmr and was evidence for the following series of reactions... 

Production of urea by cestodes suggests the existence of the urea (Krebs-Henseleit) cycle, which is shown in Fig. 6.11. One of the key enzymes, arginase, has been widely reported in cestodes (796, 185-187). However, some of the other enzymes, notably carbamyl phosphate synthetase and ornithine transcarbamyl, are either absent or present in only low amounts (39) and it is doubtful if a complete cycle operates in cestodes. It is likely that the urea excreted by tapeworms comes from the activity of arginase alone. The uric acid produced and excreted by cestodes probably arises from the breakdown of purines (39). 

Fig. 6.11. The (Krebs-Henseleit) ornithine cycle. Numbers refer to enzymes as follows. (1) Carbamyl phosphate synthetase (E.C.2.7.2.a). (2) Ornithine transcarbamylase (E.C.2.1.3.3). (3) Arginino-succinate synthetase (E.C.6.3.4.5). (4) Arginino-succinate lyase (E.C.4.3.2.1). (5) Arginase (E.C.3.5.3.1). (After Smyth, 1969.)...

CPSase catalyzes the formation of carbamyl phosphate from glutamine, bicarbonate, and two equivalents of ATP. The biosynthesis involves four partial reactions. GLNase catalyzes the formation of ammonia from glutamine. The remaining three partial reactions are catalyzed by SYNase. Bicarbonate is activated by ATP to form carboxyphosphate, which reacts with ammonia to form carbamate. The ATP-dependent phosphorylation of carbamate results in the production of carbamyl phosphate. 

Guy, H. I., and Evans, D. R. (1996). Function of the major synthetase subdomains of carbamyl-phosphate synthetase. / Biol. Chern., 271, 13762-13769. 

Biosynthesis and Utilization of Acetyl Phosphate, Formyl Phosphate, and Carbamyl Phosphate and their Relations to the Urea Cycle... 

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. 

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