title: Glucose 6-phosphate accumulation in mycobacteria: implications for a novel F420-dependent anti-oxidant defense system.
abstract: Glucose 6-phosphate (G6P) is a metabolic intermediate with many possible cellular fates. In mycobacteria, G6P is a substrate for an enzyme, F(420)-dependent glucose-6-phosphate dehydrogenase (Fgd), found in few bacterial genera. Intracellular G6P levels in six Mycobacterium sp. were remarkably higher ( approximately 17-130-fold) than Escherichia coli and Bacillus megaterium. The high G6P level in Mycobacterium smegmatis may result from 10-25-fold higher activity of the gluconeogenic enzyme fructose-1,6-bisphosphatase when grown on glucose, glycerol, or acetate compared with B. megaterium and E. coli. In M. smegmatis this coincided with up-regulation of the first gluconeogenic enzyme, phosphoenolpyruvate carboxykinase, when acetate was the carbon source, suggesting a cellular program for maintaining high G6P levels. G6P was depleted in cells under oxidative stress induced by redox cycling agents plumbagin and menadione, whereas an fgd mutant of M. smegmatis used G6P less well under such conditions. The fgd mutant was more sensitive to these agents and, in contrast to wild type, was defective in its ability to reduce extracellular plumbagin and menadione. These data suggest that intracellular G6P in mycobacteria serves as a source of reducing power and, with the mycobacteria-specific Fgd-F(420) system, plays a protective role against oxidative stress.
authors.affiliation: Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A & M Health Science Center, Kingsville, Texas 78363, USA.
authors.forename: Mohammad Rubayet
authors.initials: MR
authors.lastname: Hasan
authors.forename: Mahbuba
authors.initials: M
authors.lastname: Rahman
authors.forename: Sandford
authors.initials: S
authors.lastname: Jaques
authors.forename: Endang
authors.initials: E
authors.lastname: Purwantini
authors.forename: Lacy
authors.initials: L
authors.lastname: Daniels
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D001410:Bacillus megaterium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005816:Genetic Complementation Test; D019298:Glucose-6-Phosphate / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D009161:Mycobacterium / Q000378:metabolism*; D009285:Naphthoquinones / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D012256:Riboflavin / Q000031:analogs & derivatives / Q000737:chemistry; D024483:Vitamin K 3 / Q000737:chemistry
chemical_list: D000975:Antioxidants; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D019298:Glucose-6-Phosphate; C015084:coenzyme F420; D024483:Vitamin K 3; D012256:Riboflavin; C014758:plumbagin