Browsing by Author "NERVI, FO"

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    ACYL-COA SYNTHETASE AND THE PEROXISOMAL ENZYMES OF BETA-OXIDATION IN HUMAN-LIVER - QUANTITATIVE-ANALYSIS OF THEIR SUBCELLULAR-LOCALIZATION
    (1984) BRONFMAN, M; INESTROSA, NC; NERVI, FO; LEIGHTON, F
    The presence of acyl CoA synthetase (EC 6.2.1.3) in peroxisomes and the subcellular distribution of .beta.-oxidation enzymes in human liver were investigated by using a single-step fractionation method of whole liver homogenates in metrizamide continuous density gradients and a novel procedure of computer analysis of results. Peroxisomes contain 16% of the liver palmitoyl CoA synthetase activity, and 21% and 60% of the enzyme activity was localized in mitochondria and microsomal fractions, respectively. Fatty acyl CoA oxidase was localized exclusively in peroxisomes, confirming previous results. Human liver peroxisomes contribute 13%, 17% and 11% of the liver activities of crotonase, .beta.-hydroxyacyl CoA dehdyrogenase and thiolase, respectively. The absolute activities found in peroxisomes for the enzymes investigated suggest that in human liver fatty acyl CoA oxidase is the rate-limiting enzyme of the peroxisomal .beta.-oxidation pathway, when palmitic acid is the substrate.
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    BILE-ACID POOL CHANGES AND REGULATION OF CHOLATE SYNTHESIS IN EXPERIMENTAL DIABETES
    (1978) NERVI, FO; SEVERIN, CH; VALDIVIESO, VD
    The effect of alloxan-diabetes and insulin treatment in bile acid pool size and composition, bile acid secretion and cholic acid synthesis was investigated in the rat. The size of the cholate pool was significantly increased 4 days after diabetes induction. It reached a constant size 3 times that of control animals after 2 wk of diabetes. Changes in bile acid pool size and secretion were directly dependent on the insulin deficiency state since they were reversed by insulin treatment and were not influenced by the caloric intake of the animal nor the pharmacologic effect of alloxan. Biliary cholate secretion was also 3-fold increased in diabetic rats and it accounted for more than 80% of the total bile acids compared to 60% in the control group. The calculated daily rate of cholate synthesis was increased in diabetic rats and the circadian rhythm of cholate synthesis was abolished in this condition. The negative feedback mechanism that regulates bile acid synthesis was deleted in diabetes and was partially restored after 2 wk of insulin treatment. Bile acid metabolism was profoundly changed in alloxan-diabetic rats. Insulin may play an important role in the regulation of bile acid synthesis and intestinal absorption.
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    THE EFFECT OF PROGESTERONE ON THE REGULATORY MECHANISMS OF BILIARY CHOLESTEROL SECRETION IN THE RAT
    (1983) NERVI, FO; DELPOZO, R; COVARRUBIAS, CF; RONCO, BO
    The hypothesis was tested that progesterone [P4], an inhibitor of cholesterol esterification in liver microsomes, increases biliary cholesterol output by increasing the availability of cholesterol. Initial bile samples of 20 min were obtained from acute bile fistula rats after 7 daily doses of P4 (5-55 mg per kg of body wt). Biliary cholesterol output correlated with the doses of P4 r = 0.64 (P < 0.005). A 100% increment in biliary cholesterol output was obtained with P4 doses of 30-55 mg/kg of body wt. Under these conditions, biliary phospholipid output increased 50% (P < 0.02), but bile salt output remained normal. The relationship between biliary cholesterol and phospholipids as a function of bile salt output was studied after acute depletion of the bile salt pool. A rectangular hyperbola was the best curve fitting for the experimental data in control and P4 injected rats. In the physiological range of bile salt output, between 60 and 120 nmol/g per min, P4-injected rats secreted 100% more biliary cholesterol than did controls. The calculated theoretical maximal cholesterol and phospholipid outputs were significantly increased in P4-injected animals. Serum and hepatic cholesterol pool, free and ester fractions, remained normal. The acyl-CoA:cholesterol acyltransferase reaction was 30% inhibited in hepatic microsomes of P4-injected rats, (P < 0.05). The changes in biliary phospholipids and cholesterol output produced by P4 were rapidly reversed by either 0.5% cholesterol feeding or 2 mg/kg of body wt ethynylestradiol injection. These manipulations simultaneously produced a 100% increment in the microsomal acyl-CoA:cholesterol acyltransferase activity (P < 0.005) and increased 4-fold the concentration of hepatic cholesterol esters. This experimental model suggests a functional interrelationship between biliary cholesterol output and the rate at which the liver esterifies cholesterol.