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R Teschke

Publications and source records attributed to R Teschke.

At least 19 recordsLinked to original sources
PubMed1978

[Biochemical and pathophysiological aspects of alcohol metabolism (author's transl)].

The metabolism of ethanol to acetaldehyde proceeds in the liver via alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system (MEOS), whereas catalase plays no significant role. ADH is localized in the cytosol, required required NAD+ as cofactor and exhibits a pH optimum in the alkaline range and a Km of less than 2 mM for ethanol. Conversely, the MEOS resides in the endoplasmic reticulum, requires NADPH and O2, is inhibited by CO, and exhibits a Km of about 10 mM for ethanol. The microsomal system also metabolizes higher aliphatic alcohols such as butanol which is not a substrate for catalase. Moreover, it could be separated from ADH and catalase by column chromatography. The MEOS exhibits a variety of properties similar to those of other microsomal drug metabolizing enzymes and is characterized by inducibility of its activity following chronic alcohol consumption, which suggests the involvement of the microsomal system in the adaptive enhancement of ethanol clearance commonly observed in alcoholics.

Acetaldehyde↗
PubMed1978

[Clinical aspects of alcohol induced liver injury (author's transl)].

Chronic alcohol consumption results in early biochemical and ultrastructural alterations of the hepatocyte which in turn may lead to alcoholic fatty liver as well as alcoholic hepatitis and via the central hyaline sclerosis to fibrosis and cirrhosis of the liver. Already at the stage of the alcoholic fatty liver an isolated increase of serum gamma-glutamyltransferase activity can often be observed; it results from hepatic microsomal enzyme induction and may facilitate early recognition of alcoholic liver injury. To establish the diagnosis, however, a histological examination of the liver is necessary. The therapy of alcohol-induced liver injury is based upon an absolute alcohol abstinence since alcohol itself or one of its metabolites are hepatotoxic.

Albumins↗
PubMed1977

Metabolism of alcohol at high concentrations: role and biochemical nature of the hepatic microsomal ethanol oxidizing system.

At intermediate and higher alcohol concentrations, ethanol metabolism proceeds via alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system (MEOS), whereas catalase plays no significant role. Following prolonged ethanol consumption, an enhancement of both MEOS activity as well as the rates of ethanol metabolism occurs; the latter persisted despite inhibition of ADH by pyrazole and catalase by sodium axide, suggesting the involvement of MEOS in the adaptive increase. MEOS exhibits characteristics similar to those of other microsomal drug metabolizing enzymes and can be differentiated and isolated from both ADH and catalase activities. Reconstitution of MEOS activity was achieved with partially purified cytochrome P-450 and NADPH-cytochrome c reductase in the presence of synthetic phospholipid.

Alcohol Oxidoreductases↗
PubMed1976

Characteristics of acetaldehyde oxidation in rat liver mitochondria.

Rat liver mitochondria oxidized acetaldehyde (180 muM) at the rate of approximately 12 nmol/min/mg of protein at 37 degrees. This was stimulated by 88% with the addition of ADP. The ADP/O ratio (2.6) was similar to that with glutamate as substrate. 2,4-Dinitrophenol and phenazine methosulfate also stimulated the rate of acetaldehyde oxidation in the mitochondria. By contrast, acetaldehyde metabolism was virtually abolished by rotenone and antimycin A. These results indicate that acetaldehyde oxidation is linked to the mitochondrial respiratory chain and coupled with mitochondrial oxidative phosphorylation. Indeed, little acetaldehyde was metabolized when mitochondrial membranes were disrupted by sodium deoxycholate. In the disrupted mitochondria, however, acetaldehyde oxidation was fully recovered by addition of NAD+, suggesting that the ability of mitochondria to supply NAD+ controls the rate of acetaldehyde oxidation in intact mitochondria. The stimulatory effect of ADP on mitochondrial acetaldehyde oxidation was diminished by increasing the acetaldehyde concentration. Concomitantly, the ADP/O ratio decreased, suggesting an inhibitory effect of high concentrations of acetaldehyde on mitochondrial respiration. Chronic feeding of ethanol significantly reduced the capacity of intact liver mitochondria to oxidize acetaldehyde. This was associated with a significant reduction of the mitochondrial respiration. By contrast, the activity of aldehyde dehydrogenase in disrupted mitochondria remained unchanged.

Acetaldehyde↗
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↗