Inhibition of cellular glutathione biosynthesis by rifampicin in Mycobacterium smegmatis.
This study was carried out to investigate the mechanism of Rifampicin (RIF) induced glutathione (GSH) depletion in M. smegmatis. RIF at various concentrations decreased the activities of gamma glutamyl cysteine synthetase (GGCS) and GSH synthetase. Maximum decrease in the activities of biosynthetic enzymes of GSH was observed when 15 micrograms RIF ml-1 medium was incorporated in the growth medium before performing inoculations. The activity of GGCS was also decreased when three day grown M. smegmatis was exposed to 60 micrograms RIF ml-1 medium for a period of 6 h and 9 h. RIF did not alter the activity of gamma glutamyl transferase. The results of the present study demonstrate that the depletion caused by RIF in cellular GSH is due to its decreased biosynthesis whereas its degradation is not affected in M. smegmatis.
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
S
S
Kumar
N K
NK
Ganguly
K K
KK
Kohli
D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000096:biosynthesis*; D005981:Glutathione Synthase / Q000037:antagonists & inhibitors; D009161:Mycobacterium / Q000187:drug effects / Q000378:metabolism*; D012293:Rifampin / Q000494:pharmacology*; D005723:gamma-Glutamyltransferase / Q000187:drug effects / Q000378:metabolism
D005723:gamma-Glutamyltransferase; D005721:Glutamate-Cysteine Ligase; D005981:Glutathione Synthase; D005978:Glutathione; D012293:Rifampin