Abstract
The polyol pathway appears to be widely distributed in human tissues. In this pathway glucose is reduced to its polyol derivative, sorbital, by aldose reductase and the sorbitol then converted to fructose. NADPH seves as a co-factor for glucose reduction while NAD is a co-factor in the second step. The Km for glucose of aldose reductase is sufficiently high so that the intracellular glucose concentration regulates the rate of sorbitol and fructose synthesis. Our studies now demonstrate the presence of a sorbitol pathway in the red cell and its dependence on media of varying glucose concentrations (2–50 mM) and red cell and supernatant sorbitol and fructose measured after incubation. Red cell sorbitol and fructose rose as glucose concentration increased and fructose appeared in the media. Red cell sorbitol rose from 16.0 to 99.6 μmoles/ml as media glucose rose from 2 to 50 mM. Associated with this increase was a rise in the cell lactate to pyruvate ration (69:1 to 193:1), an increase in the percent of glucose metabolized to CO2, and an accumulation of triose phosphates and a fall of the DPG within the cell. These alterations appear to reflect changes in the pyrudine nuclcotide ratios within the cell secondary to the increased metabolism of glucose to fructose. AT high glucose concentration a significant fraction of all glucose metabolized traverses this pathway and is the first evidence that high plasma glucose concentration serves to regulate red cell metabolism. In vivo confirmation of the regulatory role of plasma glucose was provided by the demonstration of increased red cell sorbitol in patients with diabetes and hyperglycemia.
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Travis, S., Morrison, A., Clements, R. et al. The Sorbitol Pathway of the Human Erythrocyte. Pediatr Res 4, 466 (1970). https://doi.org/10.1203/00006450-197009000-00127
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DOI: https://doi.org/10.1203/00006450-197009000-00127