Liver and red-cell porphobilinogen synthase in the adult and fetal guinea pig

Abstract

Studies were undertaken to compare adult and fetal guinea pig liver and red-cell porphobilinogen synthase (EC 4.2.1.24). Specific activities of the enzyme from both liver and red-cell sources are higher in the fetus than in the adult. Age-activity profiles for the enzyme from both tissue sources are described. Porphobilinogen synthase from adult and fetal liver and red blood cells was purified utilizing discontinuous preparative disc gel electrophoresis as the final purification step. The enzyme preparations behave identically on DEAE-cellulose column chromatography. They have the same electrophoretic mobility, isoelectric point and pH optimum. Equivalent K m values are observed in the presence or absence of glutathione. Differences in inhibitory patterns between the various enzyme preparations are demonstrated by studies of inhibition by hemin, lead acetate and HgCl 2. Double-reciprocal plots for each of these inhibitors indicate certain kinetic differences between the adult and fetal liver and red-cell enzymes. These differences are abolished by the addition of reduced glutathione, in the presence of which inhibition is noncompetitive for all the enzyme preparations. Certain inhibitory properties of guinea pig porphobilinogen synthase have been shown to change as a function of age and tissue source, and an effect of added glutathione upon enzyme inhibition in vitro has been shown.