Kumar S, Ganguly N K, Kohli K K
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, UT, India.
Folia Microbiol (Praha). 1994;39(6):571-5. doi: 10.1007/BF02814111.
The mechanism of glutathione (GSH) depletion by isoniazid (INH) was studied in M. smegmatis. INH increased the activity of gamma-glutamyl transferase (GGT) whether added before medium inoculation or to actively growing cells. The activity of GGT in cells grown from the beginning in INH-containing medium increased significantly on growth days 2-6. Three-day old M. smegmatis cells treated with INH exhibited a 30-65% increase in the activity of GGT. The activities of gamma-glutamyl-cysteine synthase (GGCS) and GSH synthase (GS) were lowered by 50 and 56% respectively on the second day of growth when M. smegmatis was grown in a medium supplemented with 1.5 mg INH per L. In 3-day old M. smegmatis, INH significantly inhibited the activities of GSH biosynthetic enzymes. The results demonstrate that the increased activity of GGT and decreased activities of GSH biosynthetic enzymes are responsible for GSH depletion by INH in M. smegmatis.
在耻垢分枝杆菌中研究了异烟肼（INH）导致谷胱甘肽（GSH）耗竭的机制。无论在培养基接种前添加还是添加到活跃生长的细胞中，INH都会增加γ-谷氨酰转移酶（GGT）的活性。从一开始就在含INH的培养基中生长的细胞，其GGT活性在生长第2 - 6天显著增加。用INH处理3日龄的耻垢分枝杆菌细胞，其GGT活性增加了30 - 65%。当耻垢分枝杆菌在每升添加1.5毫克INH的培养基中生长时，γ-谷氨酰半胱氨酸合成酶（GGCS）和GSH合成酶（GS）的活性在生长第二天分别降低了50%和56%。在3日龄的耻垢分枝杆菌中，INH显著抑制了GSH生物合成酶的活性。结果表明，GGT活性增加和GSH生物合成酶活性降低是INH导致耻垢分枝杆菌中GSH耗竭的原因。
