Genetic ethanol

Biochemistry resulted from the early elucidation of the pathway of enzymatic conversion of glucose to ethanol by yeasts and its relation to carbohydrate metaboHsm in animals. The word enzyme means "in yeast," and the earfler word ferment has an obvious connection. Partly because of the importance of wine and related products and partly because yeasts are relatively easily studied, yeasts and fermentation were important in early scientific development and stiU figure widely in studies of biochemical mechanisms, genetic control, cell characteristics, etc. Fermentation yeast was the first eukaryote to have its genome elucidated. 

These findings were unexpected because previous studies had demonstrated that the y2 subunit is required for potentiation of GABAa receptor function by low concentrations of ethanol [2]. The y2 subunit gene is located within a definitely mapped quantitative trait locus (QTL) for acute alcohol withdrawal on mouse chromosome 11 [1]. Allelic variation was genetically... 

Sun F, Tsuritani 1, Yamada Y Contribution of genetic polymorphisms in ethanol-metabolizing enzymes to problem drinking behavior in middle-aged Japanese men. Behav Genet 32 229—236, 2002... 

Hood HM, Buck KJ. Allelic variation in the GABA-A receptor yl subunit is associated with genetic susceptibility to ethanol-induced motor incoordination and hypothermia, conditioned taste aversion, and withdrawal in BxD/Ty recombinant inbred mice. Alcohol Clin Exp Res 2000 24 1327-1334. 

Xu Y, Demarest K, Hitzemann R, Sike-la J. Gene coding variant in Casl between the C57BC/6J and DBA/2J inbred mouse strains Linkage to a QTL for ethanol-induced locomotor activation. Alcohol Clin Exp Res 2001, in press. Foroud T, Li T-K. Genetics of alcoholism. A review of recent studies in human and animal models. Am J Addict 1999 8 261-278. 

Monzoni A, Masutti F, Saccoccio G et al. Genetic determinants of ethanol-induced liver damage. Mol Med 2001 7 255-262. 

Alcoholism is a chronic relapsing disorder. The risk of alcoholism depends on interactions between genetic, environmental and neurobiological factors. Historically, ethanol s actions were attributed to nonspecific disruption of the lipid bilayer of neurons. It is now recognized that ethanol has specific targets, and that effects of longterm ethanol exposure are due to neuroadaptations as well as neurotoxicity [42-45]. 

Some populations, most notably East Asians, exhibit an unusual response after drinking ethanol. The symptoms include facial flushing, vasodilation, and tachycardia. These individuals apparently have a genetic deficiency of the enzyme aldehyde dehydrogenase, which leads to an accumulation of acetaldehyde even after they drink relatively small amounts of ethanol. If drugs such as metronidazole, griseofulvin, quinacrine, the hypoglycemic sulfonylureas, phenothiazines, and phenylbutazone are coadministered with ethanol, a similar accumulation of acetaldehyde may occur. 

Conversions of primary feedstocks by fermentations (such as glucose to ethanol) are not included in this book. However, fermentations are usually required to produce the enzymes or cells in the first place, and therefore chapter 5 includes a review of this type of fermentation. Chapter 5 also covers the other aspects of biocatalyst production, except immobilization and protein and genetic engineering, which are treated in chapter 6 and 7, respectively. 

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