Benzene inhibition of in vitro rabbit reticulocyte haem synthesis at delta aminolaevulinic acid synthetase: reversal of benzene toxicity by pyridoxine.
Benzene (0.113 M) inhibited haem and protein synthesis in rabbit reticulocytes. This inhibition of haem synthesis was found when L-2-[14C]-glycine was used as the radioactive precursor. However, when 4-[14C]delta-aminolaevulinic acid (ALA) was used, there was no significant inhibition. Since ALA measures the haem synthetic pathway beyond the enzyme delta-aminolaevulinic acid synthetase (ALA synthetase), these results suggest that benzene inhibits haem synthesis at or before ALA synthetase. This was confirmed by demonstrating that 1 mM ALA both protected against and reversed the benzene inhibition of reticulocyte protein synthesis. In addition, 1 mM pyridoxine both protected against and reversed the benzene inhibition of reticulocyte protein synthesis. In addition, ImM pyridoxine both protected against and reversed the benzene inhibition of reticulocyte haem and protein synthesis. These results indicate that benzene (or a metabolite) either competes with pyridoxal phosphate at ALA synthetase or competes with pyridoxine for pyridoxal phosphokinase. These results are discussed in terms of their implications for the possible roles of ALA synthetase and the haemin-controlled repressor in benzene-induced aplastic anaemia.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D001554:Benzene / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001798:Blood Proteins / Q000096:biosynthesis; D006418:Heme / Q000096:biosynthesis*; D011736:Pyridoxine / Q000494:pharmacology; D011817:Rabbits; D012156:Reticulocytes / Q000201:enzymology / Q000378:metabolism*
D001798:Blood Proteins; D006418:Heme; D000624:5-Aminolevulinate Synthetase; D001554:Benzene; D011736:Pyridoxine