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M Oratz

Publications and source records attributed to M Oratz.

At least 55 records · Page 3Linked to original sources

Effects of carbon tetrachloride on albumin synthesis.

The effects of CCl(4) on albumin synthesis were studied employing the isolated perfused liver. Carbonate-(14)C was used to measure newly synthesized albumin. 2.5 ml of CCl(4) was administered by stomach tube 2 hr before perfusion. Albumin synthesis decreased from 36 to 5 mg following the ingestion of CCl(4). Preperfusing the livers for 1 hr before measuring albumin synthesis resulted in an increase to 12 mg, and the addition of tryptophan to a final concentration of 10 mM resulted in a further increase to 19 mg. Cortisone did not protect against the toxic effects of CCl(4) when administered to the donor rabbits. Fasting resulted in an increased sensitivity to CCl(4) and an antioxidant was not effective in protecting against the toxic manifestations of CCl(4).

Albumins↗

Ethanol, acetaldehyde, and myocardial protein synthesis.

The cause of alcoholic myocardiopathy is unknown. The effects of acute exposure to ethanol or its metabolite acetaldehyde on protein synthesis in working, intact, guinea pig hearts in vitro were studied utilizing lysine-(14)C perfusion. Ethanol at 250 mg/100 ml, a level sufficient to markedly inhibit hepatic production of albumin, did not alter cardiac function, the equilibration of the intracellular free lysine pool in either ventricle, or the incorporation of lysine-(14)C into protein. Thus, in controls and ethanol-perfused hearts, the incorporation of lysine in 3 hr was 44.1+/-1.5 and 42.8+/-1.2 mumoles lysine/g protein N for the right ventricles and 25.6+/-1.0 and 24.3+/-0.8 for the left ventricles, respectively. Only at lethal levels, 1500 mg/100 ml ethanol, was protein synthesis depressed. Acetaldehyde 3.5 mg/100 ml (0.8 mM) effected a markedly positive chronotropic and inotropic effect on the perfused heart and slightly depressed equilibration of the intracellular free lysine pool. However, determinations of protein incorporation of lysine-(14)C based on intracellular lysine-(14)C specific activities showed a significant decrease from control right and left ventricle values, to 27.1+/-2.8 and 14.9+/-1.9. Propanalol, which abolished the chronotropic effect, did not prevent the inhibition of protein synthesis. The studies suggest that acetaldehyde, which inhibits cardiac protein synthesis in vitro, may play a role in alcoholic myocardiopathy by interfering with normal myocardial protein synthesis.

Acetaldehyde↗

Bile acid synthesis in the isolated, perfused rabbit liver.

These experiments were carried out to demonstrate the usefulness of the perfused rabbit liver for studies of bile acid metabolism, and to determine the rate-limiting enzyme of bile acid synthesis. Rabbits were fed a semisynthetic diet, with or without the addition of 1% cholestyramine, under controlled conditions. At the end of 2-5 wk, the livers were removed and perfused for 2.5 hr employing various (14)C-labeled precursors to measure de novo cholic acid synthesis. The livers were then analyzed for cholesterol, and the bile collected during the perfusion was analyzed for cholesterol and bile acids. Control bile contained, on the average, 0.34 mg of glycocholate, 7.4 mg of glycodeoxycholate, and 0.06 mg of cholesterol. After cholestyramine treatment of the donor rabbits, the bile contained 3.3 mg of glycocholate, 3.7 mg of glycodeoxycholate, and 0.05 mg of cholesterol. It was assumed that in cholestyramine-treated animals the enterohepatic circulation of the bile acids had been interrupted sufficiently to release the feedback inhibition of the rate-controlling enzyme of bile acid synthesis. Therefore, a given precursor should be incorporated into bile acids at a more rapid rate in livers of cholestyramine-treated animals, provided that the precursor was acted upon by the rate-controlling enzyme. It was found that the incorporation of acetate-(14)C, mevalonolactone-(14)C, and cholesterol-(14)C into cholate was 5-20 times greater in the livers of cholestyramine-treated animals than in the controls. In contrast, there was no difference in the incorporation of 7alpha-hydroxycholesterol-(14)C into cholate regardless of dietary pretreatment. It was concluded that given an adequate precursor pool, the 7alpha-hydroxylation of cholesterol is the rate-limiting step in bile acid formation.

Acetates↗

Alcohol-induced depression of albumin synthesis: reversal by tryptophan.

The influence of alcohol on albumin synthesis was studied in the isolated perfused rabbit liver. Carbonate-(14)C was used to label the intracellular arginine pool which serves as the precursor of both the carbon of urea and the guanido carbon of arginine in albumin. The control group synthesized albumin at a rate of 33 mg/100 g of wet liver weight during 2.5 hr of perfusion. When alcohol, 220 mg/100 ml, was added to the perfusate, albumin synthesis decreased to between 7 and 11 mg, less than one-third the control rate. The addition of 10 mM tryptophan to perfusates containing alcohol prevented most of the inhibitory effects and albumin synthesis increased to average 24 mg. Further, the addition of alcohol to the perfusate decreased the hepatic protein/DNA ratio from 70 to 54 and the RNA/DNA ratio from 2.3 to 1.8, changes equivalent to those seen after a 24 hr fast. The addition of tryptophan to the perfusate prevented these findings in both instances. Endoplasmic membrane-bound polysomes were examined for aggregation. Alcohol decreased the quantity of heavier aggregates. Reaggregation occurred when tryptophan was added but quantitative changes in albumin synthesis could not be related to the degree of reaggregation.

Animals↗