Iron and the liver: acute effects of iron-loading on hepatic heme synthesis of rats. Role of decreased activity of 5-aminolevulinate dehydrase.
Acute iron loading of rats, by intraperitoneal administration of iron-dextran (500 mg Fe/kg body wt 18-20 h before killing) decreased by 30% the rate of conversion of 5-amino-[14C]levulinate ([14C]ALA) into heme as measured with a recently described procedure for liver homogenates (1981. Biochem. J. 198: 595-604). The decrease in conversion of labeled ALA into heme caused by iron loading was shown to be due to a 70-80% decrease in activity of ALA dehydrase. The decrease in activity of ALA dehydrase caused by iron loading was not associated with a decrease in hepatic concentrations of GSH, nor could it be reversed by addition of dithiothreitol, Zn2+ or chelators of Fe2+ and Fe3+. Addition of FeSO4, ferric citrate, or ferritin to homogenates of control liver had no effect of activity of ALA dehydrase. The decrease in activity of ALA dehydrase, caused by iron-dextran, was mirrored by a reciprocal increase in ALA synthase. Iron-dextran potentiated the induction of ALA synthase by allylisopropylacetamide. However, this potentiation could be dissociated from the decrease in ALA dehydrase caused by iron loading.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000502:Allylisopropylacetamide / Q000494:pharmacology; D000622:Aminolevulinic Acid / Q000378:metabolism; D000818:Animals; D003911:Dextrans / Q000494:pharmacology*; D004357:Drug Synergism; D006418:Heme / Q000096:biosynthesis*; D007501:Iron / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors*; D011524:Protoporphyrins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014575:Uroporphyrinogen Decarboxylase / Q000378:metabolism
D003911:Dextrans; D011524:Protoporphyrins; D000502:Allylisopropylacetamide; D006418:Heme; D000622:Aminolevulinic Acid; D007501:Iron; D000624:5-Aminolevulinate Synthetase; D014575:Uroporphyrinogen Decarboxylase; D000623:Porphobilinogen Synthase