Developmental aspects of hepatic heme biosynthetic capability and hematotoxicity-II. Studies on uroporphyrinogen decarboxylase.
delta-Aminolevulinic acid (ALA) synthetase is considered the rate-limiting enzyme in heme biosynthesis in mature mammalian liver. However, under various physiologic or toxicologic conditions, other enzymes of the heme biosynthetic pathway may become rate-limiting in this process. In the present studies, the ontogenic development of uroporphyrinogen (uro) decarboxylase was measured in rat liver, and the properties and potential influence of this enzyme on heme biosynthetic capability in adult and fetal liver were assessed. In addition, a quantitative comparison of the activity of uro decarboxylase with that of ALA synthetase was made as a means of estimating the relative effects of specific inhibitors of uro decarboxylase on hepatic heme biosynthetic capability at each stage of development. The results indicate that fetal uro decarboxylase activity is over three times that of the adult and that enzyme activity declines to the adult levels concomitant with a decrease in the hematopoietic cell composition of the liver near the time of birth. Moreover, fetal uro decarboxylase may be substantially more susceptible to physiologic or toxicologic alteration than is the adult enzyme. The fetus may, therefore, be at greater risk with respect to compromise of heme biosynthetic capability by agents which alter uro decarboxylase activity.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D005978:Glutathione / Q000633:toxicity; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006418:Heme / Q000096:biosynthesis*; D007700:Kinetics; D008099:Liver / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D008627:Mercuric Chloride; D008628:Mercury / Q000633:toxicity; D008930:Mitochondria, Liver / Q000201:enzymology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D014575:Uroporphyrinogen Decarboxylase / Q000378:metabolism*
D006418:Heme; D008627:Mercuric Chloride; D000624:5-Aminolevulinate Synthetase; D002262:Carboxy-Lyases; D014575:Uroporphyrinogen Decarboxylase; D008628:Mercury; D005978:Glutathione