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D‐Xylulose‐induced depletion of ATP and P i in isolated rat hepatocytes
Author(s) -
Vincent M. Françoise,
Van Den Berghe Georges,
Hers HenriGéry
Publication year - 1989
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.3.7.2523832
Subject(s) - xylitol , biochemistry , intracellular , chemistry , nad+ kinase , catabolism , extracellular , purine nucleoside phosphorylase , metabolism , ribose , glycerol , purine , enzyme , fermentation
Xylitol is known to cause hepatic ATP catabolism by inducing the trapping of P i in the form of glycerol 3‐P as a consequence of an increase in the NADH:NAD + ratio, resulting from the oxidation of xylitol to d ‐xylulose. The question was therefore raised whether d ‐xylulose also depletes hepatic ATP. In isolated rat hepatocytes, 5 mM d ‐xylulose decreased ATP by 80% within 5 min compared to 40% with 5 mM xylitol. Intracellular P i decreased by 70% within the same time interval with both compounds, but was restored threefold faster with d ‐xylulose. The rate of utilization of d ‐xylulose reached 5 μmol · min −1 · g −1 of cells, as compared with 1.5 for xylitol, indicating that reduction of xylitol into d ‐xylulose is a rate‐limiting step in the metabolism of the polyol. d ‐Xylulose barely modified the concentration of glycerol 3‐P but increased xylulose 5‐P from 0.02 to 0.5 μmol/g within 5 min. The main cause of the ATP‐ and P i ‐depleting effects of d ‐xylulose was found to be an accumulation of sedoheptulose 7‐P from a basal value of 0.1 to 5 μmol/g of cells after 10 min. Ribose 5‐P increased from 0.03 to 0.5 μmol/g at 5 min. Ribose 1‐P also accumulated, albeit outside of the cells. This extracellular accumulation can be explained by the release of intracellular purine nucleoside phosphorylase from damaged hepatocytes acting on inosine that had diffused out of the cells. Smaller increases in the concentrations of sedoheptulose 7‐P and pentose phosphates were recorded after incubations of the cells with xylitol.—V incent , M. F.; V an den B erghe , G.; H ers , H‐G. d ‐Xyluloseinduced depletion of ATP and P i in isolated rat hepatocytes. FASEB J. 3: 1855‐1861; 1989.