Alcohol dehydrogenase isoenzymes

Chick J, Lehert P, Landron F, et al Does acamprosate improve reduction of drinking as well as aiding abstinence J Psychopharmacol 17 397-A02, 2003 Chrostek L, Jelski W, Szmitkowski M, et al Gender-related differences in hepatic activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in humans. J Clin Lab Anal 17 93-96, 2003... 

Maly IP, Toranelli M, Sasse D. Distribution of alcohol dehydrogenase isoenzymes in the human liver acinus. Histo-chem Cell Biol 1999 111 391-397. 

Yeast contains two cytosolic alcohol dehydrogenase isoenzymes.66 Alcohol dehydrogenase I, present in large amounts in cells undergoing fermentation,... 

Variations in the structures of enzymes within a species can also occur between and within ethnic groups of the same species. For example, a number of different alcohol dehydrogenase isoenzymes have been observed in some Asians. 

Human alcohol dehydrogenase isoenzymes have been divided into three classes. Class I isoenzymes contain a, p, yl, and y2 subunit isoenzymes, are cationic at neutral pH, and are strongly inhibited by substituted pyrazole inhibitors. Class II isoenzymes contain the 7i isoenzyme subunit, are cationic at neutral pH, and are relatively insensitive to pyrazole inhibition. Class III isoenzymes contain the X subunit, are anionic at neutral pH and are insensitive to pyrazole inhibitors. 

S. Martinovic, L. Pasa-Tolic, C. Masselon, P.K. Jensen, C.L. Stone and R.D. Smith, Characterization of human alcohol dehydrogenase isoenzymes by capillary isoelectric focusing-mass spectrometry. Electrophoresis, 21, 2368-2375 (2000). 

Kedishvili NY, Bosron WF, Stone CL, Hurley TD, Peggs CF, Thomasson HR, Popov KM, Carr LG, Edenberg HJ, Li T-K. Cloning and expression of a human stomach alcohol dehydrogenase Comparison of structure and catalytic properties with the liver isoenzymes. J Biol Chem 1995 280 3625-3630. 

Burnell JC, Bosron WF. Genetic polymorphism of human liver alcohol dehydrogenase and kinetic properties of the isoenzymes. In Crow KE, Batt RD, eds. Human Metabolism of Alcohol. Vol. 2. Boca Raton, Florida CRC Press, Inc., 1989 65-75. 

Pyruvate is initially decarboxylated into ethanal by pyruvate decarboxylase. This enzyme needs magnesium and thiamine pyrophosphate as cofactors (Hohmann 1996). Thereafter, alcohol dehydrogenase reduces ethanal to ethanol, recycling the NADH to NAD+. There are three isoenzymes of alcohol dehydrogenase in Saccharomyces cerevisiae, but isoenzyme I is chiefly responsible for converting ethanal into ethanol (Gancedo 1988). Alcohol dehydrogenase uses zinc as cofactor (Ciriacy 1996). 

Fernandez, M.J., Gomez-Moreno, C., Ruiz-Amil, M. (1972). Induction of isoenzymes of alcohol dehydrogenase in flor yeast. Arch. Microbiol, 84, 153-160. 

For example, human alcohol dehydrogenase exists in more than twenty forms.6 These isoenzymes are all dimers, and all have molecular weights of 80 kDa, or 40 kDa per subunit. The different subunits have been called the a, p, yl, y2, n, and X subunits. All of the isoenzymes catalyze the conversion of ethanol to acetaldehyde according to Eq. 10.1 ... 

H4. Harada, S., Agarwal, D. P., and Goedde, H. W., Application of gel isoelectric focusing and electrophoresis in the study of alcohol dehydrogenase and acetaldehyde dehydrogenase isoenzymes of human tissue and fibroblasts. In Electrophoresis 78 (N. Catsimpoolas, ed.), pp. 275-282. Elsevier, Amsterdam, 1979. 

LADHee and that the activity disappeared after carboxymethylation of a cysteine residue at the active site of LADH s [145]. In a recent study by Okuda and Okuda it was demonstrated that the -hydroxysteroid dehydrogenase activity in human liver was associated with a major isoenzyme of liver alcohol dehydrogenase (/82, 2) that the activity was inhibited by a chelating agent for Zn, which resides in the active site of the enzyme [146], Kinetic studies with the highly purified isoenzyme showed that neither a Theorell-Chance mechanism nor a simple ordered BiBi mechanism applied to the reaction. Evidence was obtained that the reaction was asymmetric in both directions. It has been established by Fukuba that the 4A-hydro-gen in NADH is involved [147]. 

A study of the reduction of [24- C]3-oxo-5j8-cholanic acid in bile fistula rats given [l- Hjjethanol showed that all metabolites had a 3a-hydroxy group and all radioactive products (lithocholate, 3a,6/8-dihydroxy-5 -cholanate, chenodeoxycho-late and y8-muricholate) contained about 13 atom% excess deuterium in the 3/9 position. Thus, the 3)8-hydroxy-5/9-steroid dehydrogenase isoenzyme of alcohol dehydrogenase [172] has no function in the reductive metabolism of bile acids. Cholic acid was not radioactive but contained deuterium at the 3)8, 5)8 and other positions, probably because of the transfer of deuterium from ethanol via NADH to NADPH, which it utilized in the biosynthesis of cholesterol and bile acids and in oxido reduction of the 3-hydroxyl group of the latter [173]. 

Each of the enzyme activities involved in ethanol metabolism (alcohol dehydrogenase, acetaldehyde dehydrogenase, and CYP2E1) exist as a family of isoenzymes. Individual variations in the quantity of these isoenzymes influence a number of factors, such as the rate of ethanol clearance from the blood, the degree of inebriation exhibited by an individual, and differences in individual susceptibihty to the development of alcohol-induced liver disease. 

The interaction between alcohol and vitamin A is complex. They have overlapping metabolic pathways a similar 2-step process is involved in the metabolism of both alcohol and vitamin A, with alcohol dehydrogenases and acetaldehyde dehydrogenases being implicated in the conversion of vitamin A to retinoic acid. Alcohol appears to act as a competitive inhibitor of vitamin A oxidation. In addition, chronic alcohol intake can induce cytochrome P450 isoenzymes that appear to increase the breakdown of vitamin A (retinol and retinoic acid) into more polar metabolites in the liver, which can cause hepatocyte death. So chronic alcohol consumption may enhance the intrinsic hepatotoxicity of high-dose vitamin A. Alcohol has also been shown to alter retinoid homoeostasis by increasing vitamin A mobilisation from the liver to extrahepatic tissues, which could result in depletion of hepatic stores of vitamin A. ... 

Mitochondrial malate dehydrogenase (MDH) from several species has been shown to exist in several enzymically active forms which also appear to be conformational isoenzymes (Kitto et al, 1966, 1970). Kitto et al (1970) showed, in contrast to Epstein and Schechter (1968), that these MDH s were interconvertible in vitro, had the same amino acid compositions and molecular weights, but differed, once reversibly denatured, considerably in their heat stability. Similar interconversion of isoenzymes has also been observed with purified preparations of horse liver alcohol dehydrogenase (Lutstorf and von Wartburg, 1969). The question arises if such conformers are of any physiological or functional significance. It is possible that beeause of their differences in surface charge, the various conformative isoenzymes are differently bound within a cell. 

Jomvall H, Harris JI (1970) Horse liver alcohol dehydrogenase. On the primary structure of the ethanol-active isoenzyme. Eur J Biochem 13(3) 565-576... 

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