The Genetic and Developmental Regulation of Hepatic δ-Aminolevulinate Dehydratase in Mice

Abstract The mechanism by which the levulinate locus (Lv) regulates the tissue activity of δ-aminolevulinate dehydratase in mice has been examined. The assayable hepatic enzyme activity in homozygous Lvb mouse strains represented by C57B1/6 is between one-third and one-half that of homozygous Lva strains. This difference in enzyme activity is due to a difference in amount of enzyme protein as demonstrated by immunochemical techniques with an antibody specific for δ-aminolevulinate dehydratase. Combined immunochemical and isotopic techniques show that the levulinate locus regulates the concentration of hepatic δ-aminolevulinate dehydratase by acting at the level of enzyme synthesis. The rate of degradation of hepatic enzyme is the same in both low and high activity strains; when expressed as a half-life, this is equal to 5 to 6 days. The pattern of δ-aminolevulinate dehydratase development with age is similar in livers of both low and high activity strains. The specific activity of the enzyme is high in fetal liver, decreases during the several days prior to birth, and increases to the adult level during the first 3 weeks of postnatal life. The activity of δ-aminolevulinate dehydratase in fetal liver is also regulated by the levulinate locus. The enzyme in fetal liver is approximately twice as active catalytically as the enzyme in adult liver relative to its function as an antigen. The fetal enzyme also appears to be different in stability to heat and proteolytic inactivation. However, fetal and adult enzymes are similar by other physiochemical criteria, including electrophoretic mobility, sedimentation coefficient, and Km for the substrate.