title: Ethanol-metabolizing activities and isozyme protein contents of alcohol and aldehyde dehydrogenases in human liver: phenotypic traits of the ADH1B*2 and ALDH2*2 variant gene alleles.
abstract: OBJECTIVE
  Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for the metabolism of ethanol. East Asian populations are unique in that they carry both a prevalent ADH1B*2 and a dominant-negative ALDH2*2 allele. A systematic investigation of ethanol-metabolizing activities in normal livers correlated with the corresponding functional allelic variations and protein contents of the relevant isozymes in respective enzyme families has been lacking.
  
  
  METHODS
  To obtain a reasonable sample size encompassing all possible genetic allelotypes of the ADH1B and ALDH2, 141 surgical liver specimens from adult Han Chinese were studied. Expression patterns and activities of ADH and ALDH were determined with stratification of the genetic phenotypes. Absolute protein contents as well as cellular localization of the activity and protein of ADH/ALDH isozymes were also investigated.
  
  
  RESULTS
  The activities of ADH1B*1/*2 and ADH1B*2/*2 allelic phenotypes were 5-6-fold those of the ADH1B*1/*1, suggesting that ADH1B*2 allele-encoded subunits are dominant over expression of hepatic ADH activity. The activities of the ALDH2-active phenotype were 90% higher than those of the ALDH2-inactive phenotype. Sex and age did not significantly influence the hepatic ADH and ALDH activities with specified genetic phenotypes. The isozyme protein contents were as follows in decreasing order: ADH1, ADH2, ALDH1A1, ALDH2, and ADH3. Both ADH1, but not ADH2/3, and ALDH1A1/2 showed a preferential expression in perivenular hepatocytes.
  
  
  CONCLUSIONS
  Functional correlations of ADH1B*2 and ALDH2*2 variant alleles in the liver provide a biochemical genetic basis suggesting their contribution toward variability in ethanol metabolism as well as susceptibility to alcoholism and alcohol-related diseases in East Asians.
authors: Departments of aDermatology bDentistry cPathology, Tri-Service General Hospital dDepartment of Biochemistry, National Defense Medical Center eDepartment of Emergency Medicine, Cathay General Hospital fDepartment of Surgery, Veterans General Hospital, Taipei gDepartment of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
authors: Chien-Ping
authors: CP
authors: Chiang
authors: Ching-Long
authors: CL
authors: Lai
authors: Shiao-Pieng
authors: SP
authors: Lee
authors: Wan-Lin
authors: WL
authors: Hsu
authors: Yu-Chou
authors: YC
authors: Chi
authors: Hong-Wei
authors: HW
authors: Gao
authors: Chung-Tay
authors: CT
authors: Yao
authors: Gar-Yang
authors: GY
authors: Chau
authors: Shih-Jiun
authors: SJ
authors: Yin