With fructose ingestion, there is an increased flux through the glycolytic pathway, with formation of pyruvate and lactate. As fructose-1-phosphate is formed, at the initial priming stage of glycolysis, it feeds forward and enhances the activation of pyru-vate kinase (EC 18.104.22.168), thereby facilitating the passage of fructose carbon to pyruvate and lactate. With fructose ingestion, it is common to observe increases in blood lactate concentrations.
In the postprandial state, fructose serves to promote the formation of glycogen, but only when it is consumed along with glucose. This occurs through the activation of glycogen synthase (EC 22.214.171.124) and the inhibition of glycogen phosphorylase (EC 126.96.36.199).
In the starved state, fructose actively serves as a substrate for gluconeogenesis and glucose production. The gluconeogenic pathway and the glycolytic pathway share many common intermediates and enzymes, but the direction of the carbon flux through these pathways is controlled by several allosteric enzymes unique to each pathway. Since fructose enters the glycolytic pathway beyond the major gluconeogenic-glycolytic pivotal point (the interconversion between fructose-6-phosphate and fructose-1,6-bisphosphate), it does not exert an inhibitory effect on the gluconeogenic rate-limiting enzyme, fructose-1,6-bisphosphatase (EC 188.8.131.52). Consequently, there is no inhibition of gluconeogen-esis by fructose as fructose carbons proceed through the glycolytic pathway. When a large quantity of fructose is infused intravenously, hepatic glucose production and output increase.
Consumption of large amounts of fructose is also associated with an impairment of glucose disposal. Prolonged feeding of fructose or sucrose to animals impairs insulin signaling and induces insulin resistance. Less is known about the effect of fructose ingestion on glucose tolerance and insulin resistance in humans because the scientific literature contains conflicting results. However, the lipogenic effects of fructose may contribute to insulin resistance indirectly since increased blood levels of triacylglycerols and fatty acids and deposition of lipid in liver and skeletal muscle have been implicated in the etiology of insulin resistance.
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