CONVERSION OF FRUCTOSE TO GLUCOSE IN THE RABBIT SMALL-INTESTINE - A REAPPRAISAL OF THE DIRECT PATHWAY

Gopher et al [Gopher, A., Vaisman, N., Mandel, H. & Lapidot, A. (1 990) Proc. Natl Acad. Sci. USA 87, 5449-5453] recently reported that about 50% of the glucose formed from [U-C-13]fructose infused nasogastrically in children contained C3-13 adjacent to C4-13. Assuming a high isotopic dilution of the triosephosphate pool, the authors concluded that about 50% of the fructose converted to glucose in liver and intestine bypassed the classical aldolase pathway, utilizing a hypothetical direct pathway that would involve the phosphorylation of fructose 1-phosphate to fructose 1,6-bisphosphate. The present work was undertaken in order to establish to what extent the conversion of fructose to glucose in the intestine could account for this unexpected isotopic distribution. The technique of everted sleeves was used to define the rate of conversion of [U-C-14]glucose and [U-C-14]fructose in the small intestine of 24-h-fasted rabbits. It appeared that, at the low concentration of fructose used by Gopher et al., almost as much fructose was converted to glucose as remained unmodified in the tissue. Fructose uptake was not inhibited by glucose, and the presence of all the necessary enzymes in the tissue indicated that the fructose to glucose conversion occurred by the aldolase pathway. Remarkably, this conversion operated with an isotopic dilution not exceeding 25%, due to the low rate of glucose metabolism and the near absence of gluconeogenesis from lactate. It can, therefore, be postulated that, in the presence of pure [(UC)-C-13]fructose, the triosephosphate pool is highly enriched in C-13 with little dilution by C-12, essentially giving rise to [U-C-13]glucose, as reported by Gopher et al. There is, therefore, no need to postulate the participation of a direct pathway.