Abstract
1. Loading the isolated perfused liver from well-fed rats with xylitol (20mm) caused a depletion of adenine nucleotides and Pi and an accumulation of α-glycerophosphate. The ATP content fell to 66% of the control value after 10min and to 32% after 80min. The ADP and AMP contents also fell. After 80min 63% of the total adenine nucleotides and 59% of the Pi had been lost. 2. The α-glycerophosphate content rose from 0.13 to 4.74μmol/g at 10min and reached 8.02μmol/g at 40min. 3. Xylitol was rapidly metabolized, the main products being glucose, lactate and pyruvate. 4. The [lactate]/[pyruvate] ratio in the presence of xylitol rose to 30–40. 5. On perfusion of livers from starved animals the main product of xylitol metabolism was glucose and the mean ratio xylitol removed/glucose formed was 1.29 (corrected for endogenous glucose and lactate production). This is close to the predicted value of 1.2. 6. Evidence is presented indicating that the loss of adenine nucleotides caused by xylitol is not due to the increased ATP consumption but to the accumulation of α-glycerophosphate and depletion of Pi. 7. The loss of adenine nucleotides accounts for the hyperuricaemia which can occur after xylitol infusion in man. 8. The relevance of the findings to the clinical use of xylitol as an energy source is discussed.
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- BAESSLER K. H., PRELLWITZ W., UNBEHAUN V., LANG K. [Xylitol metabolism in man. On the problem of the suitability of xylitol as a sugar substitute in diabetics]. Klin Wochenschr. 1962 Aug 1;40:791–793. doi: 10.1007/BF01481253. [DOI] [PubMed] [Google Scholar]
- Burch H. B., Lowry O. H., Meinhardt L., Max P., Jr, Chyu K. Effect of fructose, dihydroxyacetone, glycerol, and glucose on metabolites and related compounds in liver and kidney. J Biol Chem. 1970 Apr 25;245(8):2092–2102. [PubMed] [Google Scholar]
- Hems R., Ross B. D., Berry M. N., Krebs H. A. Gluconeogenesis in the perfused rat liver. Biochem J. 1966 Nov;101(2):284–292. doi: 10.1042/bj1010284. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jakob A., Williamson J. R., Asakura T. Xylitol metabolism in perfused rat liver. Interactions with gluconeogenesis and ketogenesis. J Biol Chem. 1971 Dec 25;246(24):7623–7631. [PubMed] [Google Scholar]
- KIRSTEN E., GEREZ C., KIRSTEN R. [An enzymatic microdetermination method for ammonia, specifically for extracts of animal tissues and fluids. Determination of NH4 ions in blood]. Biochem Z. 1963;337:312–319. [PubMed] [Google Scholar]
- Krebs H. A., Lund P. Formation of glucose from hexoses, pentoses, polyols and related substances in kidney cortex. Biochem J. 1966 Jan;98(1):210–214. doi: 10.1042/bj0980210. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lund P. Control of glutamine synthesis in rat liver. Biochem J. 1971 Sep;124(3):653–660. doi: 10.1042/bj1240653. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mäenpä P. H., Raivio K. O., Kekomäki M. P. Liver adenine nucleotides: fructose-induced depletion and its effect on protein synthesis. Science. 1968 Sep 20;161(3847):1253–1254. doi: 10.1126/science.161.3847.1253. [DOI] [PubMed] [Google Scholar]
- Perheentupa J., Raivio K. Fructose-induced hyperuricaemia. Lancet. 1967 Sep 9;2(7515):528–531. doi: 10.1016/s0140-6736(67)90494-1. [DOI] [PubMed] [Google Scholar]
- Raivio K. O., Kekomäki M. P., Mäenpä P. H. Depletion of liver adenine nucleotides induced by D-fructose. Dose-dependence and specificity of the fructose effect. Biochem Pharmacol. 1969 Oct;18(10):2615–2624. doi: 10.1016/0006-2952(69)90192-0. [DOI] [PubMed] [Google Scholar]
- Ross B. D., Hems R., Krebs H. A. The rate of gluconeogenesis from various precursors in the perfused rat liver. Biochem J. 1967 Mar;102(3):942–951. doi: 10.1042/bj1020942. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SMITH M. G. Polyol dehydrogenases. 4. Crystallization of the L-iditol dehydrogenase of sheep liver. Biochem J. 1962 Apr;83:135–144. doi: 10.1042/bj0830135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schumer W. Adverse effects of xylitol in parenteral alimentation. Metabolism. 1971 Apr;20(4):345–347. doi: 10.1016/0026-0495(71)90096-5. [DOI] [PubMed] [Google Scholar]
- Spitz I. M., Rubenstein A. H., Bersohn I., Bässler K. H. Metabolism of xylitol in healthy subjects and patients with renal disease. Metabolism. 1970 Jan;19(1):24–34. doi: 10.1016/0026-0495(70)90114-9. [DOI] [PubMed] [Google Scholar]
- Williamson D. H., Lund P., Krebs H. A. The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver. Biochem J. 1967 May;103(2):514–527. doi: 10.1042/bj1030514. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woods H. F., Eggleston L. V., Krebs H. A. The cause of hepatic accumulation of fructose 1-phosphate on fructose loading. Biochem J. 1970 Sep;119(3):501–510. doi: 10.1042/bj1190501. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woods H. F., Krebs H. A. The effect of glycerol and dihydroxyacetone on hepatic adenine nucleotides. Biochem J. 1973 Jan;132(1):55–60. doi: 10.1042/bj1320055. [DOI] [PMC free article] [PubMed] [Google Scholar]