Investigation into the protective mechanism of fructose during hypoxia

Fructose, but not glucose, exerts a protective effect on hepatocytes during hypoxia. This has been attributed to the fact that fructose is the superior glycolytic substrate. However, in vivo measurements indicate that fructose actually depletes cellular ATP levels in the early stages of hypoxia. We have found that D-glyceraldehyde, a unique metabolite of fructose, protects hepatocytes from chemical hypoxia (KCN) more efficiently than fructose. The L-isomer of glyceraldehyde also protects hepatocytes better than fructose, even though it is a poorer glycolytic substrate. This indicates that provision of ATP is not the sole mode of protection by these compounds. Both glyceraldehyde isomers protected isolated mitochondria from swelling under conditions that induce formation of the mitochondrial permeability transition (MPT). Our results indicate that at least part of the protective effect of fructose during hypoxia is due to glyceraldehyde inhibition of the MPT.