Effects of Rapidly Phosphorylated Substrates Fructose, Sorbitol, Xylitol (Glycerol): Toxic or Metabolic

Abstract

The metabolism of fructose and some polyols is unique in that it includes a rapid, rather unregulated, phosphorylation, an accumulation of some phosphate esters in huge concentrations and it only takes place in liver and kidney. Fructose, sorbitol and xylitol (glycerol) are used as parenteral nutrients as well as food additives. The liver and kidney are sites only for a primary metabolic conversion of the substrates to glucose and lactate, but the organs are left with a reduced level of adenine nucleotides, which lasts for hours. During the metabolic interconversion there is a change in the regulatory properties of several enzymatic steps due to effects of the accumulated fructose l-P and glycerol-P. This leads to inadequate reactions of the liver and kidney on demands from the periphery and may lead to lactic acidosis, gout or even death from accumulation of calcium oxalate. The effects described above may be greatly enhanced by e.g. hypoxia, reduced flow, exercise, biguanides, ethanol or acute severe illness. Although evidence exists that these compounds do affect liver integrity, affect some fundamental synthetic processes in liver and change liver morphology, the toxic effects seem to be extremes of metabolic changes which are well elucidated and not in themselves toxic. The strong dose-effect relationship may be changed by interaction from drugs and different physiological or pathological conditions so that the limit of toxicity is transgressed.