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J A Handler

Publications and source records attributed to J A Handler.

40 records · Page 3Linked to original sources
PubMed1985

Fatty acid-dependent ethanol metabolism.

Rates of ethanol oxidation by perfused livers from fasted female rats were decreased from 82 +/- 8 to 11 +/- 7 mumol/g/hr by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. The subsequent addition of fatty acids of various chain lengths in the presence of 4-methylpyrazole increased rates of ethanol uptake markedly. Palmitate (1 mM) increased rates of ethanol oxidation to 95 +/- 8 mumol/g/hr, while octanoate and oleate increased rates to 58 +/- 11 and 68 +/- 15 mumol/g/hr, respectively. Hexanoate, a short-chain fatty acid oxidized predominantly in the mitochondria, had no effect. Addition of oleate also increased the steady-state level of catalase-H2O2. Pretreatment of rats for 1.5 hours with 3-amino-1,2,4-triazole (1.0 g/kg), an inhibitor of catalase, prevented the ethanol-dependent decrease in the steady-state level of catalase-H2O2 completely. Under these conditions, aminotriazole decreased rates of ethanol oxidation by about 50% and blocked the stimulation of ethanol oxidation by fatty acids. Oleate decreased rates of aniline hydroxylation by about 50%, indicating that cytochrome P450 is not involved in the stimulation of ethanol uptake by fatty acids. Furthermore, oleate stimulated ethanol uptake in livers from ADH-negative deermice indicating that fatty acids do not simply displace 4-methylpyrazole from alcohol dehydrogenase. It is concluded that the stimulation of ethanol oxidation by fatty acids is due to increased H2O2 supplied by the peroxisomal beta-oxidation of fatty acids for the catalase-H2O2 peroxidation pathway.

Alcohol Dehydrogenase↗
PubMedDate not supplied

Rates of H2O2 generation from peroxisomal beta-oxidation are sufficient to account for fatty acid-stimulated ethanol metabolism in perfused rat liver.

Fatty acids generate H2O2 via peroxisomal beta-oxidation and increase ethanol metabolism markedly in a system that involves catalase-H2O2. The present studies were conducted to understand why fatty acid-stimulated ethanol metabolism occurs much faster than rates of H2O2 generation reported previously in perfused rat liver. A new method was developed to measure rates of H2O2 generation based on the fact that methanol is oxidized only by catalase in rat liver. Rates of H2O2 generation were estimated from the time necessary for the steady-state level of catalase-H2O2 measured spectrophotometrically (660-640 nm) through a lobe of the liver to return to basal values following the addition of a known quantity of methanol in a closed perfusion system containing 4% bovine serum albumin. Under these conditions, basal rates of H2O2 production and rates of 4-methylpyrazole-insensitive ethanol oxidation were in a similar range (10 to 20 mumol/g/hr). Rates of H2O2 generation were increased up to 80 mumol/g/hr by addition of laurate, palmitate or oleate (1 mM); half-maximal increases in rates were observed with 0.6 mM oleate. Hexanoate, a short-chain fatty acid, did not stimulate H2O2 production or ethanol uptake. In these studies, rates of H2O2 generation compared well with rates of fatty acid-stimulated ethanol uptake measured in the presence of 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, with all fatty acids studied. It is concluded, therefore, that rates of H2O2 generation are sufficient to account for rates of fatty acid-stimulated ethanol metabolism via catalase-H2O2. In addition, these data indicate that catalase may contribute significantly to ethanol oxidation under physiological conditions in the presence of fatty acids.

Animals↗
PubMedDate not supplied

Involvement of hormones in the swift increase in alcohol metabolism.

The purpose of this study was to determine the time course of changes in blood levels of various hormones in C57BL/6J mice during exposure to ethanol vapor. Groups of adult male mice were given 2.0 g per kg ethanol intraperitoneally or as continuous vapor for four hours and rates of ethanol elimination were measured. In parallel, blood samples were collected at timed intervals over 5.5 hours during and following exposure to ethanol. Blood levels of epinephrine, norepinephrine, corticosterone, and glucagon were elevated two- to four-fold during ethanol treatment and declined to basal values within one hour following termination of treatment. Elevated blood levels of epinephrine, norepinephrine and corticosterone were highly correlated with higher rates of ethanol elimination (r = 0.80, 0.78, and 0.72, respectively). In contrast, thyroxine and insulin levels were not affected by ethanol. These findings are consistent with the idea that acute administration of ethanol causes the release of glycogenolytic hormones which in turn increase rates of ethanol metabolism.

Animals↗