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Digestion and absorption of fructose

Fructose exists in foods as either a monosaccharide (free fructose) or as a unit of a disaccharide (sucrose). Free fructose is absorbed directly by the intestine; however, when fructose is consumed in the form of sucrose, digestion occurs entirely in the upper small intestine. As sucrose comes into contact with the membrane of the small intestine, the enzyme sucrase catalyzes the cleavage of sucrose to yield one glucose unit and one fructose unit. Fructose is absorbed in the small intestine, then enters the hepatic portal vein and is directed toward the liver.

Fructose absorption occurs on the mucosal membrane via facilitated transport involving GLUT5 (figure-1) transport proteins. Since the concentration of fructose is higher in the lumen, fructose is able to flow down a concentration gradient into the enterocytes, assisted by transport proteins. Fructose may be transported out of the enterocytes across the basolateral membrane by either GLUT2 or GLUT5, although the GLUT2 transporter has a greater capacity for transporting fructose and therefore the majority of fructose is transported out of the enterocytes through GLUT2 (figure-1).

Absorption of fructose

Figure-1- Absorption and transportation of fructose.

Clinical significance

Fructose Malabsorption- Fructose malabsorption, formerly named “dietary fructose intolerance,” is a digestive disorder in which absorption of fructose is impaired by deficient fructose carriers (GLUT 5) in the small intestine’s enterocytes. This results in an increased concentration of fructose in the entire intestine. In the large intestine, fructose that hasn’t been adequately absorbed exerts osmotic pressure, reduces the absorption of water and is metabolized by normal colonic bacteria to organic acids and the gases such as hydrogen, carbon dioxide and methane. This abnormal increase in hydrogen is detectable with the hydrogen breath test. The presence of gases and organic acids in the large intestine causes gastrointestinal symptoms such as bloating, diarrhea, flatulence, and gastrointestinal pain.

Restricting dietary intake of free fructose and/or fructose containing nutrients provides symptomatic relief in a high proportion of patients.

Metabolism of fructose

Much of the ingested fructose is metabolized by the liver, using the fructose 1-phosphate pathway (Figure-2).

1) The first step is the phosphorylation of fructose to fructose 1-phosphate by fructokinase.

2) Fructose 1-phosphate is then split into glyceraldehyde and dihydroxyacetone phosphate, the intermediates of glycolysis. This aldol cleavage is catalyzed by a specific fructose 1-phosphate aldolase.

3) Glyceraldehyde is then phosphorylated to glyceraldehyde 3-phosphate, a glycolytic intermediate, by triose kinase.

Metabolism of fructose

Figure-2- Fructose metabolism by Fructose-1-P pathway

4) Alternatively, fructose can be phosphorylated to fructose 6-phosphate by hexokinase. However, the affinity of hexokinase for glucose is 20 times as great as it is for fructose.

5) Fate of triose phosphates:

a) The two triose phosphates, dihydroxyacetone phosphate and glyceraldehyde 3-phosphate, may be oxidized by glycolysis or

b) May condense together in the presence of Aldolase to form Fructose 1, 6 bisphosphate, that may be cleaved by fructose 1, 6 bisphosphatase to  fructose-6-P.

c) Glucose-6-P  produced from Fructose-6-P by the action of Phosphohexose isomerase

i)  May be hydrolyzed to free glucose by the action of glucose-6-phosphatase, or

ii) May enter HMP pathway for the production of NADPH and pentoses, or

iii) May be converted to Glucose-1-P to be used for glycogenesis (figure-3).

Thus glucose can be produced from fructose and can contribute to blood sugar levels.

Fate of trioses

Figure-3- Interrelation of fructose and glucose metabolism. There are two isoforms of Aldolase- Aldolase A and B. Aldolase A catalyzes the cleavage of fructose 1, 6 bisphosphate in glycolytic pathway, to form two phosphorylated trioses whereas Aldolase B, concerned with fructose metabolism catalyzes the cleavage of fructose-1-P to form Glyceraldehyde and Dihydroxyacetone -P. Glyceraldehyde has to be subsequently phosphorylated for further metabolism. The fate of trioses (oxidized or used for glucose production) depends upon the cellular conditions.

To be continued….

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