Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.4.6 (urease)
 7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ornithine carbamyl transferase activity was determined by estimation of the citrulline formed during the reaction. Citrulline is estimated by diacetylmonoxime in the presence of thiosemicarbazide. The conditions of enzyme analysis were then studied in buffer veronal-acetate medium at 37 degrees C. The optimum pH for activity depended on the ornithine concentration, but was independent of carbamyl-phosphate concentration. At pH 7.8, ornithine at concentrations higher than 1.6 mM inhibited enzyme activity, ornithine Km was 0.208 mM and that of carbamyl-phosphate was 1.92 mM. The incubation time for determination of OCT activity was 15 minutes. Citrulline production was proportional to the enzyme concentration up to activities of 180 units/l. Serum urea was destroyed by a urease of high quality, so that the formation of citrulline in the control reagents was minimal. Reference values, determined on a hospital population, without liver, heart or pulmonary disease, lay between 4.7 +/- 2.3 units/l. The coefficient of variation of the technique, determined on a pool of serum of moderate activity was 8 units/l i.e. 5.1 per cent.
 ...
PMID:[Determination of the activity of serum ornithine carbamoyltranferase : working conditions in a veronal-acetate medium]. 0 89

Relative deficiencies of ornithine or arginine occur in the presence of excessive ammonia, excessive lysine, growth, pregnancy, trauma, or protein deficiency and malnutrition. Ammonia excess may occur in the presence of a normal liver when amino acid mixtures lacking ornithine, arginine, or citrulline are infused; when specific amino acids such as glycine are injected; when ammonium salts, urea, or urease are injected; or when the gastrointestinal tract contains an excess of protein, urea, or NH4+, as occurs after a gastrointestinal hemorrhage. In these states, ornithine is often rate-limiting for urea cycle function. Ornithine is also rate-limiting when ammonia excess occurs in the presence of hepatic failure. In three of the inherited urea cycle disorders, ornithine insufficiency and ammonia excess also occur. These disorders are citrullinemia, argininosuccinic aciduria, and argininemia. In the presence of excessive lysine the availability of arginine is reduced and the formation of ornithine is decreased in the liver; urea synthesis is reduced, but orotic acid synthesis is increased, and orotic aciduria results as carbamyl phosphate is directed toward the pyrimidine pathway. Hereditary lysinuric protein intolerance results in ornithine depletion, hyperammonemia, and orotic acid uria. Optimal growth in several species of animals requires 0.4-1.0% arginine in the diet. Diets deficient in arginine are associated with poor wound healing as well as stunted growth. The measurement of orotic acid excretion has been a convenient indicator of insufficiency of ornithine or arginine during growth or pregnancy in animals and should prove useful in assessing the requirement for arginine after trauma. Normal human pregnancy is associated with low-grade orotic aciduria. Protein deficiency and malnutrition increase the vulnerability of the animal or child to ammonia toxicity. This is presumably due to insufficient ornithine for normal urea cycle responsiveness.
 ...
PMID:Conditional deficiencies of ornithine or arginine. 308 83

This communication presents evidence from the literature and recent experiments that describe circumstances wherein arginine may be a conditional dietary essential. Previous work has established that the synthesis of orotic acid (OA), the first pyrimidine formed in the de novo pathway of nucleic acid synthesis, becomes elevated whenever the ammonia load exceeds the capacity of the urea cycle. Under these circumstances, the common intermediate, carbamyl phosphate, leaks from the mitochondria and induces OA synthesis in the cytoplasm. This leads to increased OA excretion in the urine as pyrimidine synthesis escapes feedback control. A deficiency of urea cycle substrates such as arginine, and administration of certain drugs, ammonium salts, urease, or excess amino acids raises orotic acid excretion. Our recent experiments in rats show that OA excretion is also elevated after partial hepatectomy following galactosamine administration, exposure to carbon tetrachloride, or feeding 36% of calories as ethanol. The elevation in OA excretion was suppressed by dietary supplementation with arginine, implying that arginine is conditionally essential. Adult human male alcoholics showed elevated urinary orotic acid-to-creatinine ratios early after drinking episodes, which declined with time following abstinence. Such evidence shows that well studied hepatotoxins and surgical liver injury affect pathways of ammonia metabolism and suggests that urinary orotic acid can be an indicator of hepatotoxicity and increased needs for arginine. Arginine-deficient diets and alcohol feeding both enhance fatty deposition in the liver, which can be worsened by high fat intakes in rats. Alcoholism, various other diseases, and fasting and realimentation change orotic acid excretion. Such responses will have to be taken into account in establishing "normal values" for OA excretion.
 ...
PMID:Orotic acid, arginine, and hepatotoxicity. 352 4