Sugar Metabolism: Glycolysis

The principal monosaccharide in humans is glucose, and the principal monosaccharide-metabolizing pathway-glycolysis-deals with glucose. We deal with other sugars, such as galactose, and fructose, and various oligomers and polymers of these three, by converting them into forms that can be processed using the pathways and enzymes in use for glucose. So to understand fructose metabolism one must find understand glucose metabolism.

Glucose monosaccharide is, suprisingly, quite uncommon in our diets; we get it in oligosaccharides and polysaccharides such as starch, glycogen, sucrose, and lactose and break these down with enzymes in the mouth and the small intestine and absorbed to produce the three major monosaccharides in body cells: glucose, fructose, and galactose (this explanation omits many intermediate steps that are well explained here: http://www.med.unibs.it/~marchesi/glycolys.html#intro).

Glucose is passed through glycolysis, then the Krebs cycle, and then finally electron transport and oxidative phosphorylation to produce the energy unit of the cell, ATP. This article is not meant to teach these pathways, so only summaries and links to the more detailed pages are provided.

Glucose is converted to two pyruvate, two ATP, and two NADH through glycolysis. A diagram and animation of glycolysis may be found here: http://www.people.virginia.edu/~rjh9u/glycol.html. Of the intermediate molecules of glycolysis, only two-fructose-6-phosphate (F6P), and glyceraldehydes-3-phosphate (G3P)- are important to this article becuase fructose will be converted into these molecules.

Each pyruvate enters the Krebs cycle, which produces four NADH, one ATP, and one FADH2 per glucose. A diagram and animation of the Krebs cycle, which shows each step, may be found at http://www.people.virginia.edu/~rjh9u/krebs.html, but for the purpose of understnading fructose metabolism the Krebs cycle might as well be considered single reaction.


The NADH and FADH2 enter the electron transport chain and power oxidative phosphorylation. This completes the conversion of glucose to ATP- thirty-eight of them. An animation of this process is provided at http://www.science.smith.edu/departments/ Biology/Bio231/ect.html, but like Krebs cycle the details are unimportant to fructose metabolism. It is enough to know that after the fructose products enter glycolysis they are treated as though they were derived from glucose.

So how does fructose enter glycolysis? The answer depends on what type of cell the fructose is in. Muscle cells have hexokinases (a type of enzyme) that will work as readily with glucose as with fructose. They add a phosphate group to fructose to produce fructose-6-phosphate (F6P), the product of the second reaction of glycolysis, and then the same enzymes and pathways used for glucose-derived F6P also handle the fructose-derived F6P.

In liver cells, the entry is more complicated. Fructose is phosphorylated to produce fructose-1-phosphate, then cleaved into two trioses: glyceraldehyde and dihydroxyacetone phosphate (DHAP). Both can be immediately converted to glyceraldehyde-3-phosphate and handed over to the glycolytic enzymes, but glyceraldehyde can also take a more roundabout and energy-consuming path. If it follows this path, it becomes glycerol, glycerol-3-phosphate, and then DHAP.

This complexity comes from the type of hexokinase present in liver cells. Unlike muscle cells, liver cells use a type of hexokinase called glucokinase, which accepts only glucose. Therefore liver cells need extra enzymes to metabolize fructose. Fructose intolerance occurs when one of these enzymes is defective.