You are not currently logged in.
Access your personal account or get JSTOR access through your library or other institution:
If You Use a Screen ReaderThis content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Selenium Regulation of Hepatic Heme Metabolism: Induction of δ -aminolevulinate Synthase and Heme Oxygenase
Mahin D. Maines and Attallah Kappas
Proceedings of the National Academy of Sciences of the United States of America
Vol. 73, No. 12 (Dec., 1976), pp. 4428-4431
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/66126
Page Count: 4
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Preview not available
Selenium was found to be a novel regulator of cellular heme metabolism in that the element induced both the mitochondrial enzyme δ -aminolevulinate synthase [succinyl-CoA:glycine C-succinyltransferase (decarboxylating); EC 184.108.40.206] and the microsomal enzyme heme oxygenase [heme, hydrogen-donor:oxygen oxidoreductase(α -methene-oxidizing, hydroxylating); EC 220.127.116.11] in liver. The effect of selenium on these enzyme activities was prompt, reaching a maximum within 2 hr after a single injection. Other changes in parameters of hepatic heme metabolism occurred after administration of the element. Thirty minutes after injection the cellular content of heme was significantly increased; however, this value slightly decreased below control values within 2 hr, coinciding with the period of rapid induction of heme oxygenase. At later periods heme content returned to normal values. Selenium treatment caused only a slight decrease in microsomal cytochrome P-450 content. However, drug-metabolizing activity was severely inhibited by higher doses of the element. Unlike other inducers of δ -aminolevulinate synthase, which as a rule are also porphyrinogenic agents, selenium induction of this enzyme was not accompanied by an increase in the cellular content of porphyrins. When rats were pretreated with selenium 90 min before administration of heme, a potent inhibitor of δ -aminolevulinate synthase production, the inhibitory effect of heme on formation of this mitochondrial enzyme was completely blocked. Selenium, at high concentrations in vitro, was inhibitory to δ -aminolevulinate synthase activity. It is postulated that selenium may not be a direct inducer of heme oxygenase as is the case with trace metals such as cobalt, but may mediate an increase in heme oxygenase through increased production and cellular availability of ``free'' heme, which results from the increased heme synthetic activity of hepatocytes. Subsequently, the increased heme oxygenase activity is in turn responsible for the lack of increase in the microsomal heme content, thus maintaining heme levels at normal values despite the highly increased activities of both heme oxygenase and δ -aminolevulinate synthase. It is further suggested that the increase in δ -aminolevulinate synthase activity is not due to a decreased rate of enzyme degradation or an activation of preformed enzyme, but to increased rate of synthesis of enzyme protein. Although selenium in trace amounts has been postulated to be involved in microsomal electron transfer process, the data from this study indicate that excess selenium can substantially inhibit microsomal drug metabolism.
Proceedings of the National Academy of Sciences of the United States of America © 1976 National Academy of Sciences