Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.5.5 (CPS)
 1,262 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased blood ammonia was induced in fasting mice by ip administration of 200 mg/kg Na-valproate followed 1 h later by 13 and 4 mmol/kg alanine and ornithine, respectively. When valproate was not used blood or liver ammonia was not increased, but increases were observed in liver glutamate (5-fold), glutamine (2-fold), aspartate (5-fold), acetylglutamate (15-fold), citrulline (35-fold), argininosuccinate (11-fold), arginine (11-fold), and urea (3-fold). The level of carbamoyl phosphate (less than 2 nmol/g) was, by far, the lowest of all urea cycle intermediates. The large increase in citrulline indicates that argininosuccinate synthesis was limiting, and that the increase in acetylglutamate induced a considerable activation of carbamoyl phosphate synthetase, which agrees with theoretical expectations, irrespective of the actual KD value for acetylglutamate. Pretreatment with valproate resulted in lower hepatic levels of glutamate, glutamine, aspartate, acetyl-CoA, and acetylglutamate. At the level found of acetylglutamate the activation of carbamoyl phosphate synthetase would be expected to be similar to that without valproate. Indeed, the levels of citrulline were similar with or without valproate. Argininosuccinate, arginine, and urea levels exhibited little if any change. Although the model used may not replicate exactly the situation in patients, from our results it appears that changes in citrullinogenesis or in other steps of the urea cycle do not account for the increase in blood ammonia induced by valproate, and it is proposed that valproate may alter glutamine metabolism.
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PMID:Changes in urea cycle-related metabolites in the mouse after combined administration of valproic acid and an amino acid load. 250 68

Citrulline, a non-protein amino acid, is present in large amounts in watermelon (Citrullus lanatus (Thunb.) Matsum. & Nakai Cucurbitaceae) fruits. Amino acid profiling of various tissues of cv. Charleston Gray during plant development confirmed progressive accumulation of citrulline only in the fruit flesh and rind tissues. Citrulline content was positively correlated with precursor (ornithine) and by-product (arginine) amino acids during fruit ripening. Genetic variation in the partitioning of citrulline and related amino acids in the flesh and rind tissues was confirmed in a sub-set of watermelon cultivars. No correlation was established between morphological fruit traits (size and rind properties) and citrulline content. To understand the regulation of citrulline accumulation, we investigated the expression of genes associated with its biosynthesis and catabolism in flesh and rind tissues during fruit development. The expression of ornithine carbamoyltransferase (OTC) involved in the ultimate step of citrulline synthesis remained steady in both tissues. The expression of N-acetylornithine aminotransferase (N-AOA) involved in the production of N-acetylornithine and N-acetylornithine deacetylase (AOD-3) involved in ornithine synthesis coincided with increasing accumulation of citrulline in flesh and rind tissues during fruit development. Down-regulation N-acetylornithine-glutamate acetyltransferase (N-AOGA) suggests the subordinate role of the non-cyclic pathway in citrulline synthesis. Eccentricity between citrulline accumulation and expression of carbamoyl phosphate synthases (CPS-1, CPS-2) during fruit development suggest that the localized synthesis of carbamoyl phosphates may not be required for citrulline synthesis. Most genes involved in citrulline break-down (Argininosuccinate synthases - ASS-1, ASS-2, and ASS-3, Argininosuccinate lyases - ASL-1, Ornithine decarboxylase - ODC, Arginine decarboxylase - ADC) were consistently down-regulated during fruit development.
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PMID:Systematized biosynthesis and catabolism regulate citrulline accumulation in watermelon. 3088 57