Evaluation of pentitol metabolism in mammalian tissues provides new insight into disorders of human sugar metabolism

Abstract

To more completely elucidate the pathways of sugar metabolism in human, we have evaluated the formation and degradation of pentitols in human fibroblasts and erythrocytes. Cultured human fibroblasts were incubated with d-arabinose, d-ribose, d-ribulose, and d-xylulose. Formation of arabitol and ribitol was analyzed by gas chromatography of the incubation medium and cell homogenate. We found that the pentoses d-arabinose and d-ribose could cross cell membranes, which indicate possible pentitol formation from extracellular pentoses. Fibroblasts formed 17 ± 4 nmol arabitol/4 days/mg protein from d-arabinose and ribitol production rates of 70 ± 15 nmol/4 days/mg protein were found after d-ribose incubation. Following d-ribulose incubation 13 nmol ribitol/4 days/mg protein was found. Human cultured fibroblasts were also incubated with d-arabitol, ribitol, and xylitol. Analyzing the incubation medium and cell homogenate revealed an absence of pentose formation. However, export of the pentitols arabitol and ribitol across the cell membrane was demonstrated, indicating that pentitols can be cleared from the body without metabolic conversion. Finally, human erythrocytes were incubated with d-/ l-arabitol, ribitol, sorbitol, and xylitol. Activities of potential pentitol dehydrogenases were evaluated by a fluorometric assay. No evidence for ribitol and arabitol degradation was observed in human erythrocytes, as compared to polyol dehydrogenase activities ranging from 1.3 to 6.1 pmol NADH/min/μl erythrocytes observed using sorbitol and xylitol. Our results indicate that ribitol and arabitol are metabolic end products in humans.