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)

We report a patient who was first diagnosed as having congenital carbamoyl-phosphate synthetase-1 (CPS-1) deficiency on the basis of significantly low CPS-1 activity in the liver at 1 year of age. We then started therapy against hyperammonaemia with little effect and, at the age of 15 years, we analysed the GLUD1 gene and found a previously reported gain-of-function mutation in the gene, resulting in a change of her diagnosis to hyperinsulinism/hyperammonaemia (HI/HA) syndrome. This case demonstrates that low CPS-1 activity in liver, however significant it might be, does not always come from a primary CPS-1 deficiency and that we have to take into consideration the possibility of a secondary CPS-1 deficiency, such as HI/HA syndrome.
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PMID:A case of hyperinsulinism/hyperammonaemia syndrome with reduced carbamoyl-phosphate synthetase-1 activity in liver: a pitfall in enzymatic diagnosis for hyperammonaemia. 1615 98

High fructose consumption is associated with the development of fatty liver and dyslipidemia with poorly understood mechanisms. We used a matrix-assisted laser desorption/ionization-based proteomics approach to define the molecular events that link high fructose consumption to fatty liver in hamsters. Hamsters fed high-fructose diet for 8 weeks, as opposed to regular-chow-fed controls, developed hyperinsulinemia and hyperlipidemia. High-fructose-fed hamsters exhibited fat accumulation in liver. Hamsters were killed, and liver tissues were subjected to matrix-assisted laser desorption/ionization-based proteomics. This approach identified a number of proteins whose expression levels were altered by >2-fold in response to high fructose feeding. These proteins fall into 5 different categories including (1) functions in fatty acid metabolism such as fatty acid binding protein and carbamoyl-phosphate synthase; (2) proteins in cholesterol and triglyceride metabolism such as apolipoprotein A-1 and protein disulfide isomerase; (3) molecular chaperones such as GroEL, peroxiredoxin 2, and heat shock protein 70, whose functions are important for protein folding and antioxidation; (4) enzymes in fructose catabolism such as fructose-1,6-bisphosphatase and glycerol kinase; and (5) proteins with housekeeping functions such as albumin. These data provide insight into the molecular basis linking fructose-induced metabolic shift to the development of metabolic syndrome characterized by hepatic steatosis and dyslipidemia.
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PMID:Proteomic analysis of fructose-induced fatty liver in hamsters. 1864 Mar 90

Hyperammonemia is a true neonatal emergency with high toxicity for the central nervous system and developmental delay. The causes of neonatal hyperammonemia are genetic defects of urea cycle enzymes, organic acidemias, lysinuric protein intolerance, hyperammonemia-hyperornithinemia- homocitrullinemia syndrome, transient hyperammonemia of the newborn, and congenital hyperinsulinism with hyperammonemia. In some of these conditions the high blood ammonia levels are due to the reduction of N-acetylglutamate, an essential cofactor necessary for the function of the urea cycle, or to the reduction of carbamoyl-phosphate synthase-I activity. In these cases, N-carbamylglutamate (carglumic acid) can be administered together with the conventional therapy. Carglumic acid is an analog of N-acetylglutamate that has a direct action on carbamoyl-phosphate synthase-I. Its effects are reactivation of the urea cycle and reduction of plasma ammonia levels. As a consequence it improves the traditional treatment, avoiding the need of hemodialysis and peritoneal dialysis. In this review we evaluate the possible field of application of carglumic acid and its effectiveness and safety.
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PMID:New developments in the treatment of hyperammonemia: emerging use of carglumic acid. 2140 88

Proteins involved in mitochondrial metabolic pathways engage in functionally relevant multi-enzyme complexes. We previously described an interaction between short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD) and glutamate dehydrogenase (GDH) explaining the clinical phenotype of hyperinsulinism in SCHAD-deficient patients and adding SCHAD to the list of mitochondrial proteins capable of forming functional, multi-pathway complexes. In this work, we provide evidence of SCHAD's involvement in additional interactions forming tissue-specific metabolic super complexes involving both membrane-associated and matrix-dwelling enzymes and spanning multiple metabolic pathways. As an example, in murine liver, we find SCHAD interaction with aspartate transaminase (AST) and GDH from amino acid metabolic pathways, carbamoyl phosphate synthase I (CPS-1) from ureagenesis, other fatty acid oxidation and ketogenesis enzymes and fructose-bisphosphate aldolase, an extra-mitochondrial enzyme of the glycolytic pathway. Most of the interactions appear to be independent of SCHAD's role in the penultimate step of fatty acid oxidation suggesting an organizational, structural or non-enzymatic role for the SCHAD protein.
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PMID:Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways. 2249 90