Regulation of delta-Aminolevulinate Synthase Activity during the Development of Oxidative Stress

P. A. Kaliman^* and T. V. Barannik

Department of Biochemistry, Kharkov State University, pl. Svobody 4, Kharkov, 310077 Ukraine; fax: (0572) 47-1816; E-mail: barannik@isc.kharkov.com

^* To whom correspondence should be addressed.

Received August 17, 1998; Revision received December 24, 1998

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Activities of rat liver delta-aminolevulinate synthetase (delta-ALAS), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH), GSH content in the liver, and the absorption spectrum of blood serum were investigated after CoCl₂, HgCl₂, or beta-adrenoblocker (propranolol) injection and after CoCl₂ and propranolol co-administration. Inhibition of the activity of the key heme biosynthesis enzyme delta-ALAS was most pronounced and prolonged during the first hours after CoCl₂ and CoCl₂ plus propranolol injections; this was associated with accumulation of Co²⁺--protoporphyrin-containing products of hemolysis. Inhibition of delta-ALAS after propranolol injection is not mediated by hemolysis. A decrease in GSH content precedes the induction of heme biosynthesis only in the case of HgCl₂ administration, and this was associated with inhibition of GR and G6PDH. The decreased GSH content during the first hours after injection of propranolol and co-administration of CoCl₂ and propranolol was not followed by increase in delta-ALAS activity 24 h after the injection. The mechanisms of the increase in the free heme content in the liver during the early stages of oxidative stress and the regulation of the key heme biosynthesis enzyme are discussed.

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KEY WORDS: delta-aminolevulinate synthase, cobalt chloride, mercuric chloride, hemopexin, reduced glutathione, heme-binding proteins, oxidative stress

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