The Urinary Excretion of Glycollic Acid and Threonic Acid by Xylitol-Infused Patients and their Relationship to the Possible Role of 'Active Glycolaldehyde' in the Transketolase Reaction in vivo

Xylitol has been used in several countries as a parenteral nutrient. Adverse reactions to intravenous xylitol infusions have been reported with calcium oxalate crystal deposition within the walls of the intracranial arteries and extensively in the kidneys (Evans et al., 1973; Schroder et al., 1974). Similar but more widespread calcium oxalate deposits occur in primary hyperoxaluria (Scowen et al., 1959). The urinary excretion of organic acids by xylitol-infused patients was examined and compared to that by glucose-infused patients, in order to define any alterations that might be related to the organic acidurias observed in patients with primary hyperoxaluria types I and I1 (hyperoxaluria with hyperglycollic aciduria and hyperglyoxylic aciduria, and hyperoxaluria with hyper-Lglyceric aciduria respectively). Quantitative extraction and g.l.c., and g.1.c.-mass-spectrometric methods were used. Four out of five of the xylitol-infused patients showed grossly increased excretions of glycollic acid and of threonic acid [2,3,4trihydroxy(threo)butanoic acid]. There was no detectable increase in the excretion of oxalic acid, glyoxylic acid, or glyceric acid. S. Hauschildt, R. A. Chalmers, A. M. Lawson, K., Schulthis & R. W. E. Watts (unpublished work) found that xylitol infusion did not increase blood oxalate concentrations. Xylitol is metabolized in man to D-XylUlOSe, D-xylulose Sphosphate, and thence to glucose via the pentose phosphate pathway. Transketolase (sedoheptulose 7-phosphateD-glyceraldehyde 3-phosphate glycolaldehydetransferase, EC 2.2.1 .l) intervenes twice in the metabolism of pentose phosphates, once to form glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate from xylulose 5-phosphate and ribose 5-phosphate, and again to form fructose 6-phosphate and glyceraldehyde 3-phosphate from another molecule of xylulose 5-phosphate and erythrose 4-phosphate (Fig. 1). In these reactions the enzyme catalyses the stereospecific reversible transfer of a glycolaldehyde moiety from a donor ketose to an acceptor aldose. Besides xylulose Sphosphate, suitable donors include hydroxypyruvate, L-erythrulose, D-fructose Gphosphate and D-sedoheptulose 7-phosphate. Suitable acceptors include, in addition to D-ribose 5-phosphate and D-erythrose +phosphate, glycolaldehyde (-+ L-erythrulose), D-glyceraldehyde 3-phosphate (-+ D-XylUlOSe 5-phosphate) and formaldehyde (-+ dihydroxyacet one).