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KMID : 0385219940040020085
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Korean Journal of Gerontology
1994 Volume.4 No. 2 p.85 ~ p.92
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Nitric Oxide Inhibits the Activity of Glyceraldehyde-3-phosphate Dehydrogenase from Salmonella paratyphi B
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Kwon Nyoun-Soo
Song Chul-Yong
Baek Kwang-Jin
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Abstract
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Nitric oxide is a major biological messenger molecule responsible for endothelium-derived vascular relaxation and neurotransmission, Nitric oxide is also known as mediator for the anti-tumor and anti-bacterial actions of macrophages, Growth-inhibitory effects of macrophage-derived nitric oxide have been demonstrated on tumor cells, intracellular trophozoites, fungi, intracellular mycobacterium, and lymphocytes. In the present study anti-bacterial effects of nitric oxide were investigated, S-Nitroso-N-acetyl-D,L-pe-nicillamine (SNAP), a nitric oxide generating agent, at the concentration of 5 mM inhibited the growth of salmonella parotyphi B in a nutrient broth by 83% in 3 h incubation at 37℃, Nitric oxide produced from SNAP inhibited the activity of S. paratyphi B glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an enzyme in the glycolytic pathway, Extension of the inhibition of GAPDH activity was dependent on the concentration of SNAP and the duration of incubation, The inhibitory effects of SNAP were almost completely abolished in the presence of reduced hemoglobin, S Nitric oxide scavenger. The cytosolic GAPDH purified from S. paratyphi B was inactivated by SNAP in the presence of NAD, At the same time, ADP-ribosyl group was attached to GAPDH, SNAP-induced inactivation of GAPDH was protected in the presence of various thiol reagents such as dithiothreitol, cysteine, and reduced glutathione, These results suggest that Nitric oxide inhibits bscterial growth by deactivating GAPDH, ADP-ribosylation of the enzyme could be a mechanism of inactivation.
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KEYWORD
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Nitric oxide, glyceraldehyde-3-phosphate dehydrogenase, salmonella paratyphi, ADP-ribosylation
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