WEAK ACID EFFECTS AND FLUORIDE INHIBITION OF GLYCOLYSIS BY STREPTOCOCCUS-MUTANS GS-5

WEAK ACID EFFECTS AND FLUORIDE INHIBITION OF GLYCOLYSIS BY STREPTOCOCCUS-MUTANS GS-5
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DOI:
10.1139/m95-108
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发表时间:
1995-09-01
影响因子:
2.8
通讯作者:
MARQUIS, RE
MARQUIS, RE
中科院分区:
生物学4区
文献类型:
--
作者:
BELLI, WA;BUCKLEY, DH;MARQUIS, RE

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氟化物和其他各种弱酸的作用可逆地降低了变形链球菌GS-5完整细胞糖酵解的耐酸性,在过量葡萄糖的酸滴实验中,最终pH值较高。药效顺序为氟化物和GT;吲哚美辛和GT;布洛芬和GT;酮洛芬和GT;水杨酸盐和GT;山梨酸酯和GT;肉桂酸酯和GT;对羟基苯甲酸酯和抗坏血酸;苯甲酸酯和抗坏血酸。只有氟化物对糖酵解酶烯醇化酶有抑制作用。然而,通透性细胞中的烯醇化酶也被酸化抑制,在pH 6-5之间活性急剧下降。有人认为,包括氟化物在内的弱酸通过促进细胞质酸化从而抑制烯醇化酶等酶来降低糖酵解酸的耐受性。根据pK(A)值、辛醇-水分配系数和分子量的知识,不能准确地预测酸的势。结果表明,它们在酸敏化过程中的作用模式除了作为质子的跨膜载体外,还包括膜功能的扰动。对羟基苯甲酸甲酯(对羟基苯甲酸甲酯)也是一种增敏剂,但效果不如母酸。
Fluoride and a variety of other weak acids acted to reduce reversibily the acid tolerance of glycolysis by intact cells of Streptococcus mutans GS-5 as shown by higher final pH values in acid-drop experiments with glucose in excess. The order of effectiveness was fluoride > indomethacin > ibuprofen > ketoprofen > salicylate > sorbate > cinnamate > p-hydroxybenzoate > benzoate > ascorbate. Only fluoride also acted as an inhibitor of the glycolytic enzyme enolase. However, enolase in permeabilized cells was also inhibited by acidification with a sharp drop-off in activity between pH 6 and 5. It was proposed that the weak acids, including fluoride, acted to reduce glycolytic acid tolerance by enhancing cytoplasmic acidification and thereby inhibiting enzymes such as enolase. The potencies of the acids could not be predicted accurately from knowledge of pK(a) values, octanol-water partition coefficients, and molecular weights. It was concluded that their modes of action in acid sensitization involved perturbations of membrane function in addition to their acting as transmembrane carriers of protons. Methylparaben (methyl ester of p-hydroxybenzoate) was also a sensitizer but was less effective than the parent acid.