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In my biology book's section on disaccharide metabolism and glycolysis, it states that sugars other than glucose must be acted upon to enter glycolysis. Let's take sucrose as an example. Sucrose is hydrolyzed in the small intestine by sucrase. The resulting fructose and glucose are absorbed and transported to the liver via the portal vein. My question concerns the fate of fructose.

To undergo glycolysis, the book states that fructose is converted into either fructose-6-phosphate (F6P) or fructose-1-phosphate (F1P). Let's say it is converted to F1P. Aldolase splits this into dihydroxyacetone phosphate and D-glyceraldehyde. Triose kinase then converts D-glyceraldehyde to glyceraldehyde-3-phosphate, a glycolytic intermediate. Where is this occurring in the body? Are we still in the liver? I can't imagine that all the fructose we consume is undergoing glycolysis in the liver. To leave the liver as a sugar, it would have had to been converted to glucose, right?

In classes I've taken, I've been told that sugars that enter the liver are pretty much all converted to glucose. Once they are converted to glucose, they can be distributed to the rest of the body, stored as glycogen, etc. If we are going straight from fructose to F1P to a glycolytic intermediate, we couldn't have left the liver. How is such a transformation even useful? Anyone care to shed some light on this?

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Where is this occurring in the body?

Almost totally in the liver.

To leave the liver as a sugar, it would have had to been converted to glucose, right?

Correct, but it's not a direct conversion.

Fructose is metabolized almost completely in the liver in humans, and is directed toward replenishment of liver glycogen and triglyceride synthesis... ...Increased concentrations of DHAP and glyceraldehyde-3-phosphate in the liver drive the gluconeogenic pathway toward glucose-6-phosphate, glucose-1-phosphate and glycogen formation. It appears that fructose is a better substrate for glycogen synthesis than glucose and that glycogen replenishment takes precedence over triglyceride formation. Once liver glycogen is replenished, the intermediates of fructose metabolism are primarily directed toward triglyceride synthesis.

So, Fructose is almost entirely made into something else first, and then that something (Glycogen or the Glycerol from triglycerides) gets broken down into Glucose or an intermediate.

Fructose stays in the liver because Fructokinase has a pretty low Km (0.5 mM) compared to Glucokinase (12mM) for Fructose, so almost all of the Fructose that enters the liver is phosphorylated into F1P - which cannot leave.

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