Biomaterial Database

Relationship between kinetics of liver alcohol dehydrogenase and alcohol metabolism. 1983

W F Bosron, and D W Crabb, and T K Li

Since alcohol dehydrogenase (ADH) catalyzes the rate-limiting step for ethanol metabolism, knowledge of the steady-state kinetics of ADH in liver is fundamental to the understanding of the pharmacokinetics of ethanol elimination. Accordingly, we have determined the kinetic properties of purified ADH isoenzymes in rat and human liver. At low ethanol concentrations, rat liver ADH obeys the Theorell-Chance mechanism and the equation predicts that activity in vivo is limited below Vmax mainly by NADH inhibition. At ethanol concentrations above 10 mM, substrate inhibition, consistent with the formation a dead-end ADH-NADH-ethanol complex, also becomes a rate-limiting factor. ADH activity, calculated from this equation and the concentrations of substrates and products present in liver during ethanol oxidation, agrees well with ethanol elimination rates measured in vivo. With human liver ADH, large differences are observed in the kinetic properties of 5 homodimeric isoenzymes: gamma 1 gamma 1 and gamma 2 gamma 2 exhibit negative cooperativity for ethanol saturation, while alpha alpha, beta 1 beta 1 and beta ind beta ind obey Michaelis-Menten kinetics. At pH 7.5, Km values for ethanol and Vmax values range 0.048 mM and 9 min-1 for beta 1 beta 1 to 64 mM and 560 min-1 for beta ind beta ind, respectively. Therefore, individuals with different ADH phenotypes should display different ethanol elimination profiles.

UI	MeSH Term	Description	Entries
D007527	Isoenzymes	Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.	Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008657	Metabolic Clearance Rate	Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.	Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D009243	NAD	A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)	Coenzyme I,DPN,Diphosphopyridine Nucleotide,Nadide,Nicotinamide-Adenine Dinucleotide,Dihydronicotinamide Adenine Dinucleotide,NADH,Adenine Dinucleotide, Dihydronicotinamide,Dinucleotide, Dihydronicotinamide Adenine,Dinucleotide, Nicotinamide-Adenine,Nicotinamide Adenine Dinucleotide,Nucleotide, Diphosphopyridine
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D004592	Electrophoresis, Starch Gel	Electrophoresis in which a starch gel (a mixture of amylose and amylopectin) is used as the diffusion medium.	Starch Gel Electrophoresis
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000426	Alcohol Dehydrogenase	A zinc-containing enzyme which oxidizes primary and secondary alcohols or hemiacetals in the presence of NAD. In alcoholic fermentation, it catalyzes the final step of reducing an aldehyde to an alcohol in the presence of NADH and hydrogen.	Alcohol Dehydrogenase (NAD+),Alcohol Dehydrogenase I,Alcohol Dehydrogenase II,Alcohol-NAD+ Oxidoreductase,Yeast Alcohol Dehydrogenase,Alcohol Dehydrogenase, Yeast,Alcohol NAD+ Oxidoreductase,Dehydrogenase, Alcohol,Dehydrogenase, Yeast Alcohol,Oxidoreductase, Alcohol-NAD+
D000429	Alcohol Oxidoreductases	A subclass of enzymes which includes all dehydrogenases acting on primary and secondary alcohols as well as hemiacetals. They are further classified according to the acceptor which can be NAD+ or NADP+ (subclass 1.1.1), cytochrome (1.1.2), oxygen (1.1.3), quinone (1.1.5), or another acceptor (1.1.99).	Carbonyl Reductase,Ketone Reductase,Carbonyl Reductases,Ketone Reductases,Oxidoreductases, Alcohol,Reductase, Carbonyl,Reductase, Ketone,Reductases, Carbonyl,Reductases, Ketone