Search PubMed⌕ Search

Biomedical subjects

R Teschke

Publications and source records attributed to R Teschke.

At least 91 records · Page 5Linked to original sources
PubMed1975

Hepatic microsomal alcohol-oxidizing system. Affinity for methanol, ethanol, propanol, and butanol.

Oxidation of methanol, ethanol, propanol, and butanol by the microsomal fraction of rat liver homogenate is described. This microsomal alcohol-oxidizing system is dependent on NADPH and molecular oxygen and is partially inhibited by CO, features which are common for microsomal drug-metabolizing enzymes. The activity of the microsomal alcohol-oxidizing system could be dissociated from the alcohol peroxidation via catalase-H2O2 by differences in substrate specificity, since higher aliphatic alcohols react only with the microsomal system, but not with catalase-H2O2. Following solubilization of microsomes by ultrasonication and treatment with deoxycholate, the activity of the microsomal alcohol-oxidizing system was separated from contaminating catalase by DEAE-cellulose column chromatography, ruling out an obligatory involvement of catalase-H2O2 in the activity of the NADPH-dependent microsomal alcohol-oxidizing system. In intact hepatic microsomes, the catalase inhibitor sodium azide slightly decreased the oxidation of methanol and ethanol, but not that of propanol and butanol, indicating a facultative role of contaminating catalase in the microsomal oxidation of lower aliphatic alcohols only. It is suggested that the microsomal alcohol-oxidizing system accounts, at least in part, for that fraction of hepatic alcohol metabolism which is independent of the pathway involving alcohol dehydrogenase activity.

1-Propanol↗
PubMed1975

Acetaldehyde oxidation by hepatic mitochondria: decrease after chronic ethanol consumption.

Prolonged consumption of ethanol significantly reduces the capacity of rat liver mitochondria to oxidize acetaldehyde. This is associated with decreased mitochondrial respiration with acetaldehyde as substrate. The reduced ability of mitochondria to metabolize acetaldehyde may explain the high levels of acetaldehyde in the blood of alcoholics, which in turn could promote the perpetuation of liver injury.

Acetaldehyde↗
PubMed1975

Effect of chronic alcohol consumption on ethanol and acetaldehyde metabolism.

Hepatic metabolism of ethanol to acetaldehyde by the alcohol dehydrogenase (ADH) pathway is associated with the generation of reducing equivalents as NADH. Conversely, reducing equivalents are consumed when ethanol oxidation is catalyzed by the NADPH dependent microsomal ethanol oxidizing system (MEOS). Since the major fraction of ethanol metabolism proceeds via ADH and since the oxidation of acetaldehyde also generates NADH, an excess of reducing equivalents is produced. This explains a variety of effects following acute ethanol administration, including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation. To the extent that ethanol is oxidized by the alternate MEOS pathway, it slows the metabolism of other microsomal substrates. Following chronic ethanol consumption, adaptive microsomal changes prevail, which include enhanced ethanol and drug metabolism, and increased lipoprotein production. Eventually, injury develops with alterations of the rough endoplasmic reticulum and structural and functional abnormalities of the mitochondria.

Acetaldehyde↗
PubMed1975

Hepatic microsomal ethanol-oxidizing system (MEOS): dissociation from reduced nicotinamide adenine dinucleotide phosphate oxidase and possible role of form I of cytochrome P-450.

The activity of the hepatic microsomal ethanol-oxidizing system (MEOS) was compared with the content of three forms of cytochrome P-450. Measurements were also made of the activity of microsomal reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the enzyme which generates H2O2 in microsomes and which has been considered by some to be the rate-limiting step of MEOS activity. Ethanol feeding to rats for 4 to 5 weeks significantly enhanced the activities of MEOS and NADPH oxidase by 102 and 62%, respectively. Concomitantly, form I of cytochrome P-450 was increased by 88% (P less than .001). Acute administration of a large dose of ethanol to animals pretreated chronically with ethanol enhanced MEOS activity by 21% (P less than .05), whereas NADPH oxidase activity remained unchanged. In addition, an acute dose of ethanol enhanced form I of cytochrome P-450 by 20% (P less than .05); thus its increase was comparable to that of MEOS activity. Pretreatment of rats with phenobarbital increased the specific activity of microsomal NADPH oxidase by 40% (P less than .05) but not that of MEOS. By contrast, CCl4 administration to rats diminished MEOS activity by 33% (P less than .01), whereas NADPH oxidase activity remained unchanged. The CCl4 treatment was found to decrease significantly all three forms of cytochrome P-450: form I by 45%, form II by 56% and form III by 24%. These results suggest that in the presence of NADPH microsomes oxidize ethanol to acetaldehyde by a process which involves, at least in part, the form I of cytochrome P-450 and in which H2O2 generation by NADPH oxidase is not the rate-limiting step.

Animals↗
PubMed1975

Differences in hepatic and metabolic changes after acute and chronic alcohol consumption.

Hepatic metabolism of ethanol to acetaldehyde by the alcohol dehydrogenase pathway is associated with the generation of reducing equivalents as NADH. Conversely, reducing equivalents are consumed when ethanol oxidation is catalyzed by the NADPH dependent microsomal ethanol oxidizing system. Since the major fraction of ethanol metabolism proceeds via alcohol dehydrogenase and since the oxidation of acetaldehyde also generates NADH, an excess of reducing equivalents is produced. This explains a variety of effects following acute ethanol administration, including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation. To the extent that ethanol is oxidized by the alternate microsomal ethanol oxidizing system pathway, it slows the metabolism of other microsomal substrates. Following chronic ethanol consumption, adaptive microsomal changes prevail, which include enhanced ethanol and drug metabolism, and increased lipoprotein production. Severe hepatic lesions (alcoholic hepatitis and cirrhosis) develop after prolonged ethanol consumption in baboons. These injurious alterations are not prevented by nutritionally adequate diets and can therefore be ascribed to ethanol rather than to dietary inadequacy.

Acetaldehyde↗
PubMedDate not supplied

Hepatic thyroid hormone levels following chronic alcohol consumption: direct experimental evidence in rats against the existence of a hyperthyroid hepatic state.

To study the effect of chronic alcohol consumption on hepatic levels of thyroid hormones, female Sprague-Dawley rats (n = 24) were pair-fed nutritionally adequate liquid diets containing either ethanol (36% of total calories) or isocaloric carbohydrates for 21 days. Compared to controls, chronic alcohol consumption failed to result in a significant change of hepatic thyroid hormone levels (thyroxine: 14.7 +/- 1.81 ng per gm of liver wet weight vs. 15.0 +/- 1.59; triiodothyronine: 2.60 +/- 0.16 ng per gm of liver wet weight vs. 2.66 +/- 0.18). Similar results were obtained when the hepatic levels of thyroid hormones were expressed per total liver, per gram of liver protein or per 100 gm of body weight. Moreover, prolonged alcohol ingestion led to a significant reduction of serum total thyroxine by 31.6% (p less than 0.001), free thyroxine by 38.9% (p less than 0.02), total triiodothyronine by 40.2% (p less than 0.001) and free triiodothyronine by 56.1% (p less than 0.001) when compared to their pair-fed controls, whereas thyroid-stimulating hormone levels remained virtually unchanged. These data, therefore, clearly show that chronic alcohol consumption is incapable of creating a hyperthyroid hepatic state in rats, and limit the rationale for antithyroid treatment in patients with alcoholic liver disease.

Alcoholism↗
PubMedDate not supplied

Sex-dependency of hepatic alcohol metabolizing enzymes.

In mature female rats the administration of testosterone led to a striking reduction of hepatic alcohol dehydrogenase activity, whereas the hepatic microsomal ethanol oxidizing system as well as catalase were both increased in activity under these experimental conditions. Conversely, estradiol left the activities of all hepatic alcohol metabolizing enzymes virtually unchanged. Ovariectomy also had little if any influence on the activity levels of the enzymes. There was a clear difference between the sexes in the hepatic alcohol metabolizing enzymes with higher enzymic activities of the microsomal ethanol oxidizing system and catalase in male than in female rats, whereas the opposite constellation was found for alcohol dehydrogenase activity. These data therefore indicate the sex-dependent nature of alcohol dehydrogenase, the hepatic microsomal ethanol oxidizing system and catalase activities in rat liver.

Alcohol Dehydrogenase↗