SUCCINYLACETONE, A POTENT INHIBITOR OF HEME-BIOSYNTHESIS - EFFECT ON CELL-GROWTH, HEME CONTENT AND DELTA-AMINOLEVULINIC-ACID DEHYDRATASE ACTIVITY OF MALIGNANT MURINE ERYTHROLEUKEMIA-CELLS
SUCCINYLACETONE, A POTENT INHIBITOR OF HEME-BIOSYNTHESIS - EFFECT ON CELL-GROWTH, HEME CONTENT AND DELTA-AMINOLEVULINIC-ACID DEHYDRATASE ACTIVITY OF MALIGNANT MURINE ERYTHROLEUKEMIA-CELLS
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DOI：
10.1016/0006-291x(79)91133-1
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发表时间：
1979-01-01
影响因子：
3.1
通讯作者：
TSCHUDY, DP
中科院分区：
文献类型：
--
作者：
EBERT, PS;HESS, RA;TSCHUDY, DP
检查4，6-二氧庚酸（琥珀酰丙酮，SA）[在遗传性酪氨酸血症患者中分泌的代谢物]抑制血红素途径的第二种酶δ-的能力。在培养的小鼠红白血病（MEL）细胞中，氨基白蛋白酸（ALA）还原酶降低血红素浓度并抑制细胞生长。SA在低至10-7 M的浓度下深刻地抑制破碎细胞制备物中的ALA脱氢酶。通过向细胞培养基中添加SA抑制了MEL细胞中DMSO [二甲基亚砜]和丁酸盐对Hb产生的刺激。当1 mM SA加入到培养基中时，ALA还原酶活性受到显著抑制，细胞的血红素浓度随着每次细胞分裂而逐渐下降。细胞分裂2次后，细胞生长明显受到抑制。
4,6-Dioxoheptanoic acid (succinylacetone, SA) [a metabolite excreted in patients with hereditary tyrosinemia] was examined with regard to its ability to inhibit the 2nd enzyme of the heme pathway, .delta.-aminoleuvulinic acid (ALA) dehydratase, lower the heme concentration and inhibit cell growth of murine erythroleukemia (MEL) cells in culture. SA profoundly inhibited ALA dehydratase in broken cell preparations at concentrations as low as 10-7 M. The stimulation of Hb production by DMSO [dimethylsulfoxide] and butyrate in MEL cells was inhibited by the addition of SA to the cell medium. When 1 mM SA was added to the medium, there was a profound inhibition of ALA dehydratase activity, and the heme concentration of cells declined progressively with each cell division. Cell growth was markedly inhibited after 2 cell divisions.