Peripheral nerve protein glycation and muscle fructolysis: evidence of abnormal carbohydrate metabolism in ALS.

Conversion of glucose to fructose via sorbitol depends upon the enzymes aldose reductase and sorbitol dehydrogenase and is called the polyol pathway. It is particularly active in muscle from patients with X-linked muscular dystrophies (15). This investigation shows enhanced metabolism of glucose to fructose in muscle from patients with ALS. Evidence is also presented showing increased activities of ketohexokinase and F-1-P splitting aldolase, which suggests that further metabolism of fructose may occur via a fructolytic pathway. Investigation of protein glycation, by an adapted fructosamine assay, in post mortem muscle, sural nerve and blood indicates that there is an increased concentration of glucose in muscle and nerve in the period prior to sampling, but blood glucose concentrations were within normal limits. The implications of fructolysis and the relationship of altered glucose metabolism in ALS are discussed.