• VandeBerg, John L (PI)

    Project: Research project

    Project Details


    The long-term objective is to enhance our understanding of
    mechanisms responsible for individual variation in rate of ethanol
    metabolism. This proposal focuses on the major enzyme of alcohol
    metabolism, alcohol dehydrogenase (ADH), and takes advantage of the
    baboon as a unique primate model in which influences of genetic
    variation and of alcohol consumption on alcohol elimination rates
    can be investigated. The specific aims are 1) to determine if
    deficiency of the liver class II ADH isozyme (ADH-4), which is
    present in some baboons but not others, is associated with reduced
    rate of alcohol clearance; 2) to determine the effect of moderate
    and moderately high levels of alcohol consumption on liver ADH
    isozyme phenotype and on rate of alcohol clearance; and 3) to
    determine the genetic basis of the liver ADH-4 deficiency that
    exists in some baboons. Baboons with and without liver ADH-4
    activity will be selected by analysis of liver biopsy samples, and
    ethanol infusion experiments will be conducted to determine the
    rate of ethanol clearance in relation to liver ADH-4 phenotype.
    Alcohol feeding studies will be undertaken with baboons, using the
    Lieber-DeCarli liquid diet technique, to determine the influence
    of moderate and moderately high alcohol consumption on changes in
    liver ADH phenotype, monitored by liver biopsy, and on changes in
    ethanol clearance rate determined by ethanol infusion. The genetic
    basis of ADH-4 deficiency will determined by typing ADH-4 activity
    levels in liver samples of pedigreed baboons that have been
    necropsied and of those from which biopsies will be taken for this
    project. The results of these experimental manipulations, not
    possible with human subjects, will provide new insights that can
    be applied to understanding the ways in which heredity and alcohol
    consumption affect rate of alcohol metabolism in humans.
    Effective start/end date4/1/893/31/90


    • National Institutes of Health


    • Medicine(all)


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