Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dibutyryl cyclic adenosine 3':5'-monophosphate (DBcAMP) has been reported to cause numerous alterations in the activity of hepatic monooxygenase enzymes following in vivo administration or in vitro addition to intact liver preparations. In the present report the effect of the nucleotide on metabolism of p-nitroanisole (pNA) and aniline was studied in isolated rat hepatocytes. Initial studies indicated that in vitro addition of DBcAMP to hepatocytes increased metabolism of both pNA and aniline as determined by the production of oxidized metabolites, p-nitrophenol (pNP) and p-aminophenol, respectively. After enzymatic hydrolysis with beta-glucuronidase and arylsulfatase, it was determined that DBcAMP had increased accumulation of pNP formed from pNA by inhibiting further metabolism via conjugation reactions. Further studies using pNP directly as substrate confirmed the finding and revealed that glucuronidation was more sensitive to the inhibitory effect of DBcAMP than was sulfation. The 8-bromo derivative of cAMP was more potent than DBcAMP at inhibiting glucuronidation, whereas cyclic AMP and dibutyryl cyclic guanosine 3':5'-monophosphate were without effect. Noncyclic adenine nucleotides (ATP, ADP, AMP) also altered pNA and pNP metabolism. ATP and ADP increased pNP accumulation from pNA while ATP and AMP inhibited glucuronidation of pNP. DBcAMP was further found to decrease UDP-glucuronic acid levels in a concentration-dependent manner without disrupting the redox state (NAD+/NADH) in hepatocytes. The data suggest that adenine nucleotides exert a nonspecific inhibition upon glucuronidation and sulfation reactions.
 ...
PMID:Inhibition of glucuronidation and sulfation by dibutyryl cyclic AMP in isolated rat hepatocytes. 287 57

The mechanism by which various chemicals induce renal cystic disease is unknown. To examine the early events in cystogenesis the ultrastructure and biochemistry of liver and kidney were analyzed after the administration of a chemical that induces renal cyst formation. Special emphasis was placed on examining potential mechanisms that would account for the observed loss of extracellular proteoglycans. Renal cystic disease was chemically induced in rats by feeding 2-amino-4,5-diphenylthiazole (DPT) for up to 4 weeks. After 4 days of feeding, DPT had induced a 4-fold increase in total urine output relative to diet-restricted control groups. Both groups maintained, but did not gain, weight during the feeding schedule. Cyst formation was localized to the medullary collecting tubules. Relative to diet-restricted controls, rats fed DPT exhibited diminished renal and hepatic catalase activity, but elevated activity for UDP-glucuronosyltransferase. Medulla showed an increase in the specific activities of the enzymes galactosyltransferase and sulfatase B. These enzymological findings correlated with ultrastructural observations of a loss of peroxisomes, proliferation of endoplasmic reticulum and enlargement of the golgi apparatus. Serum and urinary levels of inorganic sulfate were significantly increased in DPT-fed rats relative to controls. Tissue levels of UDP-glucuronic acid and adenosine 3'-phosphate 5'-phosphosulfate were not depressed by DPT feeding. Thus, DPT-induced cyst formation and loss of staining for glycosaminoglycans does not involve gross depletions of UDP-glucuronic acid and adenosine 3'-phosphate 5'-phosphosulfate, mutual cosubstrates for Phase II drug conjugation reactions and glycosaminoglycan synthesis.
 ...
PMID:Diphenylthiazole-induced changes in renal ultrastructure and enzymology: toxicologic mechanisms in polycystic kidney disease? 311 18