Fructose and Mannose Degradation

This pathway illustrates the shared catabolic fates of both fructose and mannose. Fructose occurs naturally in foods as a free monosaccharide and as a component of the disaccharide sucrose. It is also widely used as a sweetener. In the body, fructose is converted to dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate in a sequence of three reactions. First, fructose is phosphorylated, then cleaved by aldolase to yield dihydroxyacetone phosphate and D-glyceraldehyde, which is phosphorylated to yield D-glyceraldehyde 3-phosphate. The cleavage of fructose 1-phosphate is catalyzed by the same enzyme that catalyzes the reversible cleavage of fructose 1,6-bisphosphate in glycolysis. The isoform of this enzyme found in liver, kidney, and intestine (B) is approximately equally active with fructose 1-phosphate and fructose 1,6-bisphosphate as substrates, while the muscle and brain isoforms (A and C, respectively), have little activity with fructose 1-phosphate. Fructose metabolism thus occurs mainly in tissues expressing the B isoform. Compared to fructose, mannose is not well metabolized in humans and it does not significantly enter most carbohydrate metabolism pathways when taken orally. Indeed it appears that 90% of mannose ingested is excreted unconverted into the urine within 30 – 60 minutes, with 99% of the remainder being excreted within the following 8 hours. On the other hand, mannose is present in numerous glycoconjugates including N-linked glycosylated proteins. What little mannose is metabolized appears to be phosphorylated and either converted to GDP mannose and sent on to N-glycan biosynthesis or it is isomerized by mannose-6-phosphate isomerase into beta-fructose-6-phosphate, which then can be directed into the fructose catabolic pathway. #

References

1. Lehninger, A.L. (2005) Lehninger principles of biochemistry (4 ^th ed.). New York: W.H Freeman.
2. Salway, J.G. (2004) Metabolism at a glance (3 ^rd ed.). Alden, Mass. : Blackwell Pub.