Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of gender as a variable that might affect the metabolism of ethanol and thus the consequences of ethanol metabolism is reviewed. First, the pharmacodynamics of ethanol are reviewed. Specific differences between males and females relative to ethanol pharmacokinetic parameters are discussed including gender differences in the volume of distribution and putative hormonal effects on achieved blood alcohol levels. In addition, attention is directed toward the metabolic capacity of alcohol dehydrogenase and the microsomal ethanol oxidizing system with respect to effects of both sex differences and hormonal manipulations on the activities of these ethanol metabolizing enzymes. Finally, the data upon which the concept of sex-related differences in susceptibility to alcohol induced end organ failure are presented.
Adv Alcohol Subst Abuse 1988
PMID:Ethanol, its metabolism and gonadal effects: does sex make a difference? 306 89

Using protein and enzymatic methods, a major role in ethanol metabolism was assigned to the alcohol dehydrogenase (ADH) enzymes. Three major classes of ADHs were described on the basis of structure and function, including timing and location of expression. Polymorphic variants, including a common functional variant, were identified. Molecular cloning allowed the demonstration of a high degree of sequence homology between the three class I ADH genes and enabled the definition of ADH variants at the DNA sequence level. The existence of an ADH gene cluster on chromosome 4 and the shared evolutionary roots of these genes suggests that the continued integration of studies of the different ADH genes will yield further insights into alcohol metabolism in humans.
Adv Alcohol Subst Abuse 1988
PMID:Review of the molecular biology of the human alcohol dehydrogenase genes and gene products. 306 90

Pyrazole and 4-methylpyrazole are potent inhibitors of liver alcohol dehydrogenase and as such have been proposed as potential antidotes to alcohol poisoning. These drugs are also inducers of hepatic cytochrome P-450. We tested pyrazole and four 4-substituted pyrazoles for their potential as inducers of cytochrome P-450 and drug metabolism in mature male rats. Total cytochrome P-450 was significantly increased (p less than 0.05) 1.3 fold by treatment with 4-methylpyrazole. P-nitrophenol hydroxylase (PNPH) activity (nmol/min/mg protein) was increased 1.9 fold following treatment with pyrazole and with 4-methylpyrazole. Treatment with 4-methylpyrazole also resulted in a 2.9 fold increase in ethoxyresorufin demethylase (EROD) activity. In addition, pyrazole treatment led to a significant decrease in the activity of benzphetamine demethylase. 4-Iodopyrazole increased the turnover (nmol/min/nmol P-450) of EROD and PNPH by 1.5 fold each. 4-Nitropyrazole had no significant effect on any of the activities or turnover rates tested. In contrast to results with cultured chick hepatocytes, where induction was directly related to the hydrophobicity of the 4-substituent, the present data indicate that the process of induction of in vivo is more complex.
Adv Alcohol Subst Abuse 1988
PMID:Induction of rat hepatic microsomal drug metabolizing enzymes by pyrazole and 4-substituted pyrazoles. 322 28

Adult male and female rats were subjected to gonadectomy by means of surgical removal of the gonads. In the male, castration resulted in a significant decrease in both body and liver weights compared to intact controls, which persisted for at least 3 weeks. Conversely, ovariectomy was associated with a significant enhancement in both growth rate and liver weight from intact controls. Castration of male rats resulted in induction of hepatic L-ADH (cytosolic alcohol dehydrogenase) and L-ALDH (cytosolic aldehyde dehydrogenase) as contrasted with inhibition of mitochondrial ALDH which was evident in the enzyme with the apparent high Km. Kinetic studies indicate that there was an increase in apparent Km of L-ADH, and hence reduced affinity to hepatic metabolism of ethanol as a consequence of castration in the male rat. This is compared with few changes occurring in the apparent Km value of L-ALDH. Ovariectomy did not alter endogenous L-ADH or L-ALDH. Short-term administration of a synthetic estrogenic steroid ethinyl estradiol, inhibited liver mitochondrial ALDH in the intact female rat but not in the ovariectomized female. Short-term administration of the same dose of an androgen, testosterone, did not alter specific activities of the liver enzymes measured in the intact or in the castrated male rat. Administration of both components of OCs (oral contraceptives) combined or the estrogen alone in behavioral experiments profoundly reduced ethanol drinking by voluntary intake of diluted ethanol solution by the intact female rat. These results suggest a hepatic-gonadal link may exist and that a toxic interaction between the OCs and alcohol drinking is definitely possible.
Res Commun Subst Abuse 1980
PMID:Studies on ethanol and oral contraceptives: feasibility of a hepatic-gonadal link. 1231 Sep 79