The effect of dietary inorganic sulfate on the activity of glucose-6-phosphate dehydrogenase in rat liver

The effect of the level of dietary inorganic sulfate (So₄=) on the activity of rat liver glucose-6-phosphate dehydrogenase (G6pDH), as measured by the appearance of NADPH, was investigated. Male rats of a Long-Evans, Wistar, Sprague Dawley mixed strain were fed 15% casein diets containing 0.0002% S0 0.02% S0 (optimum level), or 0.42% SO ₄ with total sulfur kept constant with either methionine or cysteine, or with constant cysteine. Preliminary tests using 350 to 450 g rats fed the test diets for periods of 17 or 22 days showed significantly higher (P < 0.l) enzyme activities at the 0.0002% SO ₄ level than at the 0.02% SO ₄ level, with no difference between the 0.02% level and the 0.42% level when total sulfur was kept constant with methionine supplementation. When cysteine was kept constant, no differences in enzyme activity between the diets were observed. If, instead of 350 g to 450 g rats, 150 g to 250 rats were used, and the diets were fed for an average of 32 days, maximum enzyme activities were observed at the O.02% level of SO ₄, when total dietary sulfur was kept constant with methionine supplementation. When dietary sulfur was kept constant with cysteine supplementation, no significant differences in enzyme activity were observed and when cysteine was kept constant, there was a significant increase (P < O.05) from the low So ₄ level to the high level.

Since oxidized glutathione (GssG) has been implicated in the control of G6PDH activity, GssG levels were measured by a manometric technique in the supernatants of the livers of the 150 to 250 g rats. Also, the in vitro effect of physiological levels of GSsG on G6PDH activity was tested. When dietary sulfur was kept constant by methionine supplementation, GssG levels were found to decrease significantly (P < 0.05) with increasing dietary SO ₄ levels. In vitro, GSSG did not completely eliminate the differential effect of SO ₄ on G6PDH activity. Thus, it was concluded that GsSG levels could only partially account for the decrease in G6PDH activity at SO ₄ levels above the optimum and could not account for the decrease in activity at the low sulfate level. When dietary sulfur was kept constant with cysteine supplementation, a significant decrease (P < O.l) in the GssG level was observed at the high level of dietary sulfate only. When dietary cysteine was kept constant, there were no differences in GssG levels, thus GSsG levels did not account for the G6PDH effect.

Glutathione peroxidase (GSH-Px) and glutathione

rats were also measured. As the SO ₄ level was decreased below the optimum level, GSH-Px and GsSG-R activities decreased; however, above the optimum level of So GSSG-R activities continued to increase slightly but GSH-Px levels dropped, explaining the decrease in GssG levels at a sulfate level above the optimum level.

The in vitro effects of physiological levels of S0 on the differential effect of dietary sulfate on G6PDH was also tested. Like GSSG, SO ₄ only reduced the differential effect of sulfate when total sulfur was kept constant with methionine supplementation, but did not eliminate it. The increase in G6PDH activity with increasing dietary SO ₄ was not affected by in vitro SO ₄ when dietary cysteine was kept constant.