GSBS Student Publications

Title

Synergistic induction of delta-aminolevulinate synthase by glutethimide and iron: relationship to the synergistic induction of heme oxygenase

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences

Date

11-15-1991

Document Type

Article

Medical Subject Headings

5-Aminolevulinate Synthetase; Animals; Cells, Cultured; Chick Embryo; Drug Synergism; Enzyme Induction; Ferric Compounds; Glutethimide; Heme; Heme Oxygenase (Decyclizing); Iron; Liver; Metalloporphyrins; Nitrilotriacetic Acid

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Relationships between activities of delta-aminolevulinate synthase and heme oxygenase, respectively the rate-limiting enzymes of heme biosynthesis and degradation, have been studied in chick embryo liver cell cultures following exposure of the cultures to glutethimide and iron, a combination known to produce a synergistic induction of both enzymes. In time-course experiments, synergistic induction of heme oxygenase activity by glutethimide and iron preceded that of delta-aminolevulinate synthase by 4 h. Effects of selective inhibitors of both heme synthesis and degradation have also been studied with respect to effects on delta-aminolevulinate synthase and heme oxygenase activities. The synergistic induction of heme oxygenase by glutethimide and iron appears to be dependent upon cellular heme synthesis because addition of inhibitors of heme biosynthesis, 4,6-dioxoheptanoic acid or N-methyl-mesoporphyrin abolishes this synergistic induction. Exposure of cultures to tin-mesoporphyrin, a potent inhibitor of heme oxygenase, prevented the synergistic induction of delta-aminolevulinate synthase produced by glutethimide and iron, or, when added after induction was already established, promptly halted any further induction. These results suggest that the level of activity of heme oxygenase can reciprocally modulate intracellular heme levels and thus activity of delta-aminolevulinate synthase.

Rights and Permissions

Citation: Biochim Biophys Acta. 1991 Nov 15;1080(3):245-51.

Related Resources

Link to article in PubMed

Journal Title

Biochimica et biophysica acta

PubMed ID

1954232