Mechanism of thiamine-induced respiratory deficiency in Saccharomyces carlsbergensis.
Cells of Saccharomyces carlsbergensis 4228 grown aerobically with added thiamine (1 microgram . ml-1) in a vitamin B6-free medium contained no detectable heme precursors, such as delta-aminolevulinate, coproporphyrin III, or protoporphyrin IX. The deficiency in heme precursors in the thiamine-grown cells was accompanied by previously reported phenomena, i.e., growth depression, vitamin B6 deficiency, and respiratory deficiency due to a marked decrease in the activities of heme-containing enzymes and cytochrome level (I. Nakamura et al., FEBS Lett. 62: 354-358, 1976). It has been reported that all of the effects of thiamine are abolished by adding pyridoxine to the medium. delta-Aminolevulinate was found to have quite similar effects to those of pyridoxine, except that growth was partially improved by delta-aminolevulinate, whereas it was fully restored by pyridoxine. Incubation of the thiamine-grown cells with delta-aminolevulinate resulted in the appearance of the heme precursors and the heme-containing enzymes. Consistent with the lowered amount of vitamin B6, the thiamine-grown cells had a lowered activity of delta-aminolevulinate synthase, a pyridoxal phosphate-dependent enzyme. Not only the holoenzyme activity but also the apoenzyme activity was very low in these cells. These results indicate that the thiamine-induced vitamin B6 deficiency brings about the decrease in delta-aminolevulinate synthase activity, which leads to heme deficiency and therefore to respiratory deficiency.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000378:metabolism / Q000494:pharmacology; D003306:Coproporphyrins / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis*; D011524:Protoporphyrins / Q000378:metabolism; D011736:Pyridoxine / Q000378:metabolism*; D012440:Saccharomyces / Q000378:metabolism*; D013831:Thiamine / Q000494:pharmacology*
D003306:Coproporphyrins; D003580:Cytochromes; D011524:Protoporphyrins; C026971:coproporphyrin III; D006418:Heme; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D000624:5-Aminolevulinate Synthetase; D011736:Pyridoxine; D013831:Thiamine