Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of 1-benzylimidazole on the activities of hepatic monooxygenases cytochromes P-450 dependent, epoxide hydrolases and UDP-glucuronosyltransferases was investigated in male Wistar rats. Several doses (25, 75 and 100 mg/kg/day) were administered gastrically during 5 days in order to evaluate the dose-related induction. The treatment caused a dose-dependent hepatomegaly. 1-Benzylimidazole decreased the plasma level in triglycerides by 60-70%; by contrast the cholesterol content was not changed during the time course of the experiment. Lauric acid hydroxylase, benzphentamine N-demethylase, 7-ethoxyresorufin O-deethylase, 7-ethoxycoumarin O-deethylase activities were increased 3.5-, 4-, 13- and 46-fold, respectively with the highest dose. By immunoblotting, an enhancement in the protein bands corresponding to cytochromes P-450c and P-450b could be simultaneously observed, whatever the dose administered, thus suggesting an induction process. However, 1-benzylimidazole failed to bind with high affinity to the cytosolic Ah receptor. On the other hand, measurement of the activity of the microsomal epoxide hydrolase with benzo(a)pyrene-4,5-oxide as substrate and quantitation of the enzyme protein by immunoassay revealed that the increase in the activity after treatment with the compound was the result of enzyme activation only. By contrast, cytosolic epoxide hydrolase was not affected by 1-benzylimidazole. This compound also stimulated three distinct forms of UDP-glucuronosyltransferase. The activities towards 4-methylumbelliferone, 1-naphthol, morphine or a monoterpenoid alcohol, nopol, supported by two different isozymes were significantly increased only with the highest dose; meanwhile bilirubin glucuronidation was 2-fold enhanced, whatever the dose used. These observations emphasize the variety of the effects of 1-benzylimidazole on drug-metabolizing enzymes.
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PMID:Effect of 1-benzylimidazole on cytochromes P-450 induction and on the activities of epoxide hydrolases and UDP-glucuronosyltransferases in rat liver. 284 Sep 13

Various metabolic studies were performed in a patient with the idiopathic Fanconi syndrome in whom constant ketonuria suggested that organic acidemia might contribute to the metabolic acidosis. Glucose intolerance with a diminished insulin release was found after PO or IV glucose loads and after glucagon administratio. An insulinopenic "diabetes-like" state has not previously been described in such patients. The patient had impaired galactose-glucose interconversion, elevated blood lactate levels, reduced pyruvate levels, and an increased lactate:pyruvate ratio. Hepatomegaly and hypoglycemia were not present, and liver and muscle biopsies revealed no enzymatic evidence of glycogenosis. The erythrocyte UDP galactose transferase activity was normal. The patient failed to convert fructose to glucose and had a rise in blood lactate after ethanol administration. Further studies revealed no production of glucose after alanine or glycerol administraion, each test being associated with elevated blood lactate levels and, after alanine, an increased lactate:pyruvate ratio. The lactate:pyruvate ratio was elevated after glucagon administration with increased lactate and reduced pyruvate concentrations.
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PMID:Abnormalities of carbohydrate metabolism in idiopathic Fanconi syndrome. 738 41

Classical galactosaemia (Mendelian Inheritance in Man, no 230400) is an autosomal recessive disorder of galactose metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT). The GALT enzyme is responsible for the conversion of galactose-1-phosphate with UDP glucose to glucose-1-phosphate and UDP galactose. The gene encoding for GALT is located on chromosome 9p13. Patients present with hepatomegaly, liver failure, food intolerance, hypoglycaemia, muscle hypotonia, sepsis and cataract. Treatment involving the total restriction of lactose-containing foods is life-saving but many patients develop late complications such as problems of mental development, disorders of motor function, disorders of speech and hypergonadotrophic hypogonadism.
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PMID:[From gene to disease; galactosemia and galactose-1-phosphate uridyltransferase deficiency]. 1475 29