Ethanol human liver alcohol dehydrogenase

Yeast and mammalian alcohol dehydrogenases differ in substrate specificity and catalytic activity. The yeast enzyme is more specific for acetaldehyde and ethanol, but mammalian enzymes have a broad substrate specificity, and even with primary alcohols maximum activity is not observed with ethanol. Because of the large amount of alcohol dehydrogenase present in human liver and its role in alcohol metabolism in man, human liver alcohol dehydrogenase is of particular interest. It was first purified by Wartburg et and crystallized by Mourad and Woronick. Human liver alcohol dehydrogenase is a dimer with subunit structures analogous to those of horse liver, and each subunit probably contains two zinc atoms. Several different types of human ADH have been isolated. with minor variations in amino acid... 

Zinc deficiency in humans is difficult to diagnose because a suitable functional test, or a test for zinc reservoirs, has been lacking, Milne et ai. (1987) documented that a variety of zinc-requiring enzymes of the red blood cell seem to resist the effects of dietary zinc deficiency, but demonstrated that liver alcohol dehydrogenase may be sensitive to the deficiency. The activity of this enzyme was assessed by a functional test — the ethanol tolerance test. The ethanol tolerance test would be expected to be influenced by factors unrelated to zinc status, such as the state of Induchon of the ethanol oxidizing system, and hence may not be the functional test of choice for assessing zinc status. 

The discovery of the steroid-active isozymes of horse liver alcohol dehydrogenase (Sections II,A,l,a and II,A,l,d) also established that 3-keto-and 3 3-hydroxysteroids are substrates, but the functional significance of this is not clear. Since this activity also seems to be present in the rat enzyme (9) and in all isozymes of the human enzyme (W), it may be more important than previously realized when the horse ethanol-active isozyme was the most studied form. It may also be noted that mammalian livers contain many different specific steroid dehydrogenases (11). Structural studies have established that mammalian alcohol dehydrogenases have a distant evolutionary link to both the yeast (ff) and bacterial enzymes (IS). 

Alcohol dehydrogenase is present in many organisms that metabolize ethanol, including humans. In human liver it catalyzes the oxidation of ethanol, either ingested or produced by intestinal microorganisms, with the concomitant reduction of NAD+ to NADH. 

The primary enzymes that metabolize alcohol in the human liver are alcohol dehydrogenase and CYP2E1. Acetaldehyde, a primary metabolite of ethanol, may have direct fibrogenic activity, and... 

The multiplicity of isozyme patterns of alcohol dehydrogenase in human liver (Section II,A,2), together with racial and acquired differences in ethanol metabolism (31,32), have attracted great interest. No clear correlation has, however, so far been found between patterns of alcohol dehydrogenase isozymes and ethanol metabolism (33) or alcoholism. 

In humans, most of ingested ethanol is oxidized to acetaldehyde in the liver by alcohol dehydrogenase (ADH) ... 

Many enzymes incorporate one or more metal ions as essential parts of their structure. Different metalloenzymes make use of ions of magnesium, calcium, manganese, iron, cobalt, copper, zinc, or molybdenum. For example, the molecule of alcohol dehydrogenase (molecular mass 87000 d), which catalyzes the oxidation of ethanol to acetic acid in the human liver, contains two atoms of zinc, and the amylase in human saliva contains an atom of calcium (Ca" " ). Some enzyme molecules contain several metal atoms, which may be of different kinds. An example is cysteamine oxidase, which catalyzes the oxidation of cysteamine, HSCH2CH2NH2 this enzyme contains an atom of iron, an atom of copper, and an atom of zinc. 

The human toxicology of methanol has been studied [6,71,72]. The skin absorption rate has been reported to be 0.19 m cm2/min [73]. Methanol vapor uptake by the lungs is effective, usually 7080% (74). In the liver, methanol goes through oxidation metabolism catalyzed by alcohol dehydrogenase (an enzyme), producing toxic formaldehyde and formic acid. The accumulation of formic acid leads to acidosis, dama g the nervous system, particularly the optic nerves, and the retina. In the copresence of ethanol, ethanol is selectively metabolized by alcohol dehydrogenase over methanol this delays methanol intoxication and allows detoxication by the natural elimination of methanol via respiration and urination. The methanol elimination half-life is about 23 h [6]. Because of the slow elimination, methanol can be re rded as a cumulative poison [68]. Chronic oq)osure may result in sufficient methanol accumulation in the body, and illness. 

In human liver cells, the enzyme alcohol dehydrogenase (LADH) catalyzes the oxidation of ethanol to yield acetaldehyde. In this reaction, the coenzyme nicotinamide adenine dinucleotide, NAD, is converted to its reduced form, NADH. 

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