Heme biosynthesis and drug metabolism in mice with hereditary hemolytic anemia

Abstract

Mice homozygous for the nb (normoblastosis) gene have severe hemolytic anemia characterized by increased catabolism were measured in the tissues of homozygous (nb/nb), heterozygous (+/nb), and control (+/+) mice generated on the same genetic background. The functional capacity of the microsomal hemeprotein, cytochrome P-450, was also determined in the livers of these animals. Mice homozygous for the nb gene defect had a marked increase in protoporphyrin content, delta-aminolevulinic acid (ALA)-dehydratase, and uroporphyrinogen I (URO)-synthase activities in erythrocytes. Lesser increases were observed in liver and spleen of nb/nb mice. The homozygous mice also had a marked increase in microsomal heme oxygenase activity in the liver, kidney, and spleen compared to normal controls. The increase in heme oxygenase activity is attributable to a higher specific activity per mg of microsomal protein in the case of the liver and the kidney and to the marked organamegaly in the case of the spleen.