Rapid stimulation of hepatic microsomal heme oxygenase in selenium-deficient rats. An effect of phenobarbital.
Hepatic microsomal heme oxygenase, the rate-limiting enzyme in heme degradation, is rapidly and markedly stimulated in selenium-deficient rats but not in controls, after a single injection of phenobarbital sodium. This stimulation occurred as early as 2 h and reached an 8- to 10-fold maximum 6 h following the drug. These observations suggest that phenobarbital rapidly and markedly enhances the degradation of hepatic heme in selenium deficiency. The cause for this rapid phenobarbital-mediated stimulation of heme degradation was investigated. It could not be ascribed to either accelerated turnover of cytochrome P-450, or enhanced lipid peroxidation possibly resulting from the concomitant lack of glutathione peroxidase in selenium deficiency. For these reasons, the metabolism of hepatic heme in the selenium-deficient rat liver was further examined during the 6-h period following phenobarbital. These studies indicated that whereas heme was synthesized much faster and to a greater extent in the selenium-deficient rat liver than in the control, its utilization in the formation of hemoproteins such as cytochrome P-450 and tryptophan pyrrolase was apparently impaired in selenium deficiency. Such defective utilization of heme in the 6-h period following phenobarbital could effectively result in a relative excess of unutilized "free" heme; hence the consequent stimulation of microsomal heme oxygenase for its disposal.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D006418:Heme; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D012643:Selenium / Q000172:deficiency*
D006418:Heme; D008748:Methylcholanthrene; D006899:Mixed Function Oxygenases; D000624:5-Aminolevulinate Synthetase; D012643:Selenium; D010634:Phenobarbital