Understanding Fructose and Human Metabolism

April 22/Obesity, Fitness & Wellness Week -- According to recent research from Leeds, U.K., "A molecular understanding of the unique aspects of dietary fructose metabolism may be the key to understanding and controlling the current epidemic of fructose-related obesity, diabetes and related adverse metabolic states in Western populations. Fructose catabolism is initiated by its phosphorylation to fructose 1-phosphate, which is performed by ketohexokinase (KHK)."

"Here, the crystal structures of the two alternatively spliced isoforms of human ketohexokinase, hepatic KHK-C and the peripheral isoform KHK-A, and of the ternary complex of KHK-A with the substrate fructose and AMP-PNP are reported. The structure of the KHK-A ternary complex revealed an active site with both the substrate fructose and the ATP analogue in positions ready for phosphorylation following a reaction mechanism similar to that of the pfkB family of carbohydrate kinases. Hepatic KHK deficiency causes the benign disorder essential fructosuria," wrote C.H. Trinh and colleagues, University of Leeds.

The researchers concluded, "The effects of the disease-causing mutations (Gly40Arg and Ala43Thr) have been modelled in the context of the KHK structure."

Trinh and colleagues published their study in Acta Crystallographica Section D - Biological Crystallography ("Structures of alternatively spliced isoforms of human ketohexokinase." Acta Crystallographica Section D - Biological Crystallography, 2009;65(Part 3):201-211).

For additional information, contact S.E.V. Phillips, University of Leeds, Institute Molecular & Cellular Biology, Astbury Center Structural Molecular Biology, Leeds LS2 9JT, W Yorkshire, U.K.

From the April 27, 2009, Prepared Foods E-dition