Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The blood levels of zinc, lead, copper and albumin and the activity of erythrocyte delta-aminolevulinic acid dehydratase (ALA D), with and without addition of zinc in vitro, were measured in healthy subjects and in patients with cirrhosis. In cirrhosis there was a decrease, of zinc (-40%) albumin (-38%) and of activity of ALA D (-48%) and an increase in blood lead (+80%). Correlation between these results has been studied. The increase of blood lead is probably the result of zinc decrease. Moreover, as the urinary excretion of zinc is enhanced by chelation therapy, the prescription of zinc in lead intoxication is to be recommended. The activity of ALA D in patients with cirrhosis is less enhanced by addition of zinc in vitro than is the activity in patients intoxicated with lead. Probably in cirrhosis there is especially a decrease in the synthesis of ALA D, and lead intoxication the enzyme is inhibited.
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PMID:[The relationship between zinc levels in blood and the activity of delta-amino-levulinic acid dehydratase in human erythrocytes (author's transl)]. 88 56

Liver transplantation is the only effective treatment for hereditary tyrosinaemia type I (McKusick 276700). We have treated one acute and four subacute-chronic cases with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27), to prevent the formation of maleylacetoacetate and fumarylacetoacetate and their saturated derivatives. The oral daily dose was 0.1-0.6 mg/kg. The excretion of succinylacetoacetate and succinylacetone decreased from 15-103 mmol/mol creatinine to the detection limit or slightly above (ie, to 20-150 mumol/mol creatinine). The concentration of succinylacetone in plasma decreased from 5.8-43 mumol/l to the detection limit (0.1 mumol/l) over 2-5 months of treatment. The almost complete inhibition of porphobilinogen synthase in erythrocytes was abolished and the excretion of 5-aminolevulinate decreased to within or slightly above the reference range. The concentration of alpha-fetoprotein decreased in four patients to 1.3-7.5% of initially high values over 6-8 months. Improved liver function was reflected by normal concentrations of prothrombin complex and in decreased activities of alkaline phosphatase and gamma-glutamyltransferase in serum. Computed tomography revealed regression of hepatic abnormalities in three patients. One patient developed rickets 6 months before treatment and had excreted high concentrations of markers of tubular dysfunction--after 3 weeks of treatment, this excretion had disappeared. No side-effects were encountered. Inhibition of 4-hydroxyphenylpyruvate dioxygenase may prevent the development of liver cirrhosis and abolish or diminish the risk of liver cancer. Normalisation of porphyrin synthesis will eliminate the risk of porphyric crises. This type of treatment may thus offer an alternative to liver transplantation in hereditary tyrosinaemia.
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PMID:Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenase. 135 48

Rats fed chow containing finely divided elemental iron (from carbonyl-iron) develop hepatic iron overload resembling human hereditary hemochromatosis in that deposition of iron is primarily in periportal hepatocytes and with hepatic iron concentrations sufficiently high to be associated in the human disease with hepatic fibrosis or cirrhosis. In recent studies using this model, we reported changes in hepatic hemoproteins and heme oxygenase, the rate-controlling enzyme of heme breakdown. We now report effects of iron-loading on three enzymes of heme synthesis: 5-aminolevulinate synthase; the first and rate-controlling enzyme of the pathway, 5-aminolevulinate dehydrase (or porphobilinogen synthase), and uroporphyrinogen decarboxylase, the activity of which is decreased in porphyria cutanea tarda, a liver disease in which iron is known to play an important but still poorly understood role. Of the three enzymes, only activity of the dehydrase was altered by iron-loading: it was decreased significantly as early as 1 week after starting iron feeding, and with marked iron overload was 30 to 32% of control values. The degree of decrease was inversely related (r = -0.77 to -0.88) to the degree of iron overload and was partially reversed within 1 to 3 days when feeding of the iron-supplemented diet was stopped. The decrease in dehydrase activity was not attributable to lack of reduced glutathione or other disulfide-reducing agents or to zinc deficiency; nor was evidence found for inhibition by iron compounds or other possible inhibitors present in iron-loaded livers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic heme synthesis in a new model of experimental hemochromatosis: studies in rats fed finely divided elemental iron. 367 87

Delta-Aminolevulinate synthase and delta-aminolevulinate dehydratase activities were determined in liver biopsy specimens obtained from 12 patients with hepatic cirrhosis. Delta-Aminolevulinate synthase activity was determined by the incorporation of [1,4-14C]succinyl coenzyme A into delta-aminolevulinate. The mean activity of delta-aminolevulinate synthase was significantly higher in cirrhotic liver specimens (mean +/- SE, 193.7 +/- 34.5 picomoles delta-aminolevulinate per milligram protein per 30 minutes) than in controls with minimal histologic changes (32.7 +/- 13.6, p less than 0.01). Furthermore, the mean activity of delta-aminolevulinate synthase was higher in micronodular cirrhosis (281.6 +/- 58.8) than in the other types of cirrhosis (131.0 +/- 23.1, p less than 0.05). Levels of indocyanine green retention at 15 min correlated with the activity of hepatic delta-aminolevulinate synthase (p less than 0.05). The mean activity of delta-aminolevulinate dehydratase, in contrast, was significantly lower in cirrhotic liver specimens (9.4 +/- 1.3 nanomoles porphobilinogen per milligram protein per hour) than in controls (22.0 +/- 2.6, p less than 0.05). These results suggest that the extent of liver injury or the degree of portosystemic shunting, or both, influence the rate of hepatic heme biosynthesis.
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PMID:Changes in aminolevulinate synthase and aminolevulinate dehydratase activity in cirrhotic liver. 684 3