Alcohol dehydrogenase (ADH) is an enzyme. Since then, there has been extensive research on the enzyme.Alcohol dehydrogenase is a dimer, weighing 80 kDa. Alcohol dehydrogenases (EC 188.8.131.52) are a group of seven dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of NAD+ to NADH.
See Blood alcohol content for rates of metabolism.
Reaction catalysed An alcohol + NAD <=> an aldehyde or ketone + NADH
Wikigenes ADH human
SYNTHESIS AND TURNOVER
Regulation of gene expression of class I alcohol dehydrogenase by glucocorticoids
In the presence of ethanol, alcohol dehydrogenase I (AHH I) is induced and alcohol dehydrogenase II (ADH II) is repressed. ADH I and ADH II have molecular weights of 39,000 and 36,000 respectively. At least ADH I is under the control of alcR, a transacting regulatory gene that is adjacent to alcA (the structural gene for ADH I, Pateman et al. 1983). Mutations in the alcR regulatory gene result in non inducibility of ADH I specific mRNA. Extreme alcA and alcR mutations result in derepressed levels of ADH II, and it is not clear whether alcR controls ADH II directly or through its control of ADH I synthesis. Both enzymes are subject to carbon catabolite repression. Induction of ADH I and ADH II operates at the level of synthesis or processing of mRNA.
The regulation of mRNA production for the yeast positive activator ADR1, a gene required for the expression of the glucose-repressible alcohol dehydrogenase (ADH II), was studied. ADR1 mRNA levels did not vary when yeasts were switched from glucose- to ethanol-containing medium, while ADH II expression increased 100-fold. The mRNA for the ADR1-5c allele, which augments ADH II expression 60-fold during glucose repression, was not present in greater abundance than ADR1 mRNA.
The 5' region of this cDNA is interesting: the AUG that initiates the ADH polypeptide is preceded by an AUG that would encode the first amino acid of a tripeptide. Presumably termination of this tripeptide is followed by reinitiation at the AUG immediately preceding the sequence of the
the ubiquitin–proteasome pathway plays a role in the degradation of ADH and in the enhanced degradation of this enzyme by DHT.
Locus Location ADH1A chr4:100,424,853-100,431,165
Locus Location ADH1B chr4:100,446,550-100,461,595
Locus Location ADH1C chr4:100,476,672-100,492,940
Chemical structure and images
Protein Aminoacids Percentage
The Protein Aminoacids Percentage gives useful information on the local environment and the metabolic status of the cell (starvation, lack of essential AA, hypoxia)
cellular localization, stomach and in the liver
In humans, it exists in multiple forms as a dimer and is encoded by at least seven different genes. There are five classes (I-V) of alcohol dehydrogenase, but the hepatic form that is primarily used in humans is class 1. Class 1 consists of A,B, and C subunits that are encoded by the genes ADH1A, ADH1B, and ADH1C. The enzyme is contained in the lining of the stomach and in the liver. It catalyzes the oxidation of ethanol to acetaldehyde:
CH3CH2OH + NAD+ ? CH3CHO + NADH + H+
The ADH class I forms constitute the classical enzyme responsible for the liver ethanol metabolism, whereas the ADH class III form is a ubiquitous glutathione-dependent formaldehyde dehydrogenase. Both these classes are well established in structure, variability, internal architecture, origin, and function , with class III as a probable ancestor and class I reflecting a duplicatory emergence at early vertebrate times .
ADH class IV exhibits a unique epithelial tissue distribution and is the characteristic stomach ADH, where it has been suggested to function in the first-pass metabolism of ethanol (7). More importantly, however, class IV has been ascribed a special function, based on its high activity with retinol , in the regulation of retinoic acid formation and hence in regulation of cellular growth and differentiation in vertebrates.
Vitamin A (retinaldehyde) and Alcohol Abuse
Chronic ethanol consumption leads to vitamin A deficiency but also to enhanced toxicity of vitamin A and beta-carotene when supplemented. Changes in retinol metabolism due to alcohol may have a pathophysiological impact in both alcoholic liver disease and alcohol associated cancer as retinoic acid, the most active form of vitamin A, is an important regulator of normal epithelial cell growth, function, and differentiation. Under normal conditions, ingested retinol is metabolised to retinaldehyde via cytosolic alcohol dehydrogenase (ADH), microsomal retinol dehydrogenase (three types), and several types of cytosolic retinol dehydrogenases, and retinaldehyde is further oxidised to retinoic acid via aldehyde dehydrogenase (ALDH). Retinoic acid binds to retinoic acid receptors (RAR), initiating intracellular signal transduction leading to a cascade of events and finally to a decrease in cell regeneration
Involved subunits and Active site
The substrate is coordinated to the zinc; and this enzyme has two zinc atoms per subunit. One is the active site, which is involved in catalysis.
Alcohol dehydrogenase is also involved in the toxicity of other types of alcohol: for instance, it oxidizes methanol to produce formaldehyde and ethylene glycol to ultimately yield glycolic and oxalic acids. Humans have at least six slightly different alcohol dehydrogenases. All of them are dimers (consist of two polypeptides), with each dimer containing two zinc ions Zn2+. One of those ions is crucial for the operation of the enzyme: it is located at the catalytic site and holds the hydroxyl group of the alcohol in place.
Isoenzyme class I (liver) et class IV (stomach)
The most important form of gastric ADH is isoenzyme of class IV, less important is the isoenzyme of class III.
ADH classes I and II seem to have no role in the stomach.
Alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide, also known as ADH7, is a human gene.
This gene encodes class IV alcohol dehydrogenase 7 mu or sigma subunit, which is a member of the alcohol dehydrogenase family.
The enzyme encoded by this gene is inefficient in ethanol oxidation, but is the most active as a retinol dehydrogenase;
thus it may participate in the synthesis of retinoic acid, a hormone important for cellular differentiation.
The expression of this gene is much more abundant in stomach than liver, thus differing from the other known gene family members
ALCOHOL DEYDROGENASE ACTIVITY
Varies between men and women, between young and old, and between populations from different areas of the world. The level of activity may not only be dependent on level of expression but due to allelic diversity among the population. These allelic differences have been linked to region of origin. For example, populations from Europe have been found to express an allele for the alcohol dehydrogenase gene that makes it much more active than those found in populations from Asia or the Native Americas. This may be a correlating evolution with the rise of aldehyde dehydrogenase, which has been suggested as one of the more recognizable recent evolutionary changes in humans (along with lactose tolerance) - in order to make water safe in cities too dense to use springs, Europeans fermented alcoholic (and hence antiseptic) beverages, while Asians typically boiled their water (creating, among other things, tea). This selected for those who didn't suffer from violent alcohol flush response in European populations.
variation in alcohol dehydrogenase with alcohol dependence in Native Americans
ASSOCIATIONS AND INTERACTIONS
To examine the association between ADH1B, ADH1C, and ALDH2 polymorphisms and head and neck cancer, we undertook a pooled analysis of all relevant studies.