Journal of Clinical Investigation
Geisel School of Medicine
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.
Bonkowsky HL, Healey JF, Sinclair PR, Sinclair JF, Shedlofsky SI, Elder GH. Iron and the liver: acute effects of iron-loading on hepatic heme synthesis of rats. Role of decreased activity of 5-aminolevulinate dehydrase. J Clin Invest. 1983;71(5):1175-1182. doi:10.1172/jci110866
Dartmouth Digital Commons Citation
Bonkowsky, H L.; Healey, J F.; Sinclair, P R.; Sinclair, J F.; Shedlofsky, S I.; and Elder, G H., "Iron and the Liver: Acute Effects of Iron-Loading on Hepatic Heme Synthesis of Rats. Role of Decreased Activity of 5-Aminolevulinate Dehydrase." (1983). Dartmouth Scholarship. 3614.