Liver fructose metabolism

Outside of the liver, fructose is channeled into the sugar metabolism by reduction at C-2 to yield sorbitol and subsequent dehydration at C-1 to yield glucose (the polyol pathway not shown). 

The rate of fructose metabolism is more rapid than that of glucose because the trioses formed from fructose 1 -phosphate bypass phosphofructokinase—the major rate-limiting step in glycolysis (see p. 97). [Note Loading the liver with fructose, for example, by intravenous infusion, can significantly elevate the rate of lipogenesis, caused by the enhanced production of acetyl CoA.]... 

In liver, the cells contain mainly glucokinase instead of hexokinase and this enzyme phosphorylates only glucose. Thus in liver, fructose is metabolized instead by the fructose 1-phosphate pathway (Fig. 2). 

Figure 16.15. Fructose Metabolism. Fructose enters the glycolytic pathway in the liver through the fructose 1-phosphate pathway.

In the organism, D-fructose metabolizes into glycogen, animal starch being the energy reservoir stored in the liver. 

Liver is the principal site of D-fructose metabolism. D-Fructose is transported to the liver from the small intestine by way of the portal blood-vessel. Experiments with perfused pig and rat livers revealed that the rate of elimination of D-fructose from blood is a function of the sugar concentration,26,27 and follows Michaelis-Menten kinetics.27,28 Carrier-mediated, liver-membrane transport of D-fructose has a high29 Km and Vmax, in comparison to the intracellular phosphorylation constants of D-fructose in both pigeon and rat livers.27,28 For example, the calculated rat-liver transport for D-fructose has a Km of 67 mM and a Vmax of 30 /u,mole.min. g-1, in contrast to the lower, calculated fruc-tokinase Km of 1.0 mM and Vmax of 10.3 pmole. min r1. g 1 with D-fruc-tose and Km of 0.54 mM with adenosine 5 -triphosphate (ATP). In perfused pig-liver,28 the transport Km for D-fructose is only ten times that of intracellular phosphorylation by fructokinase. Hence, D-fructose-transport values suggested that, at physiological D-fructose concentrations, membrane transport limits the rate of uptake, thereby protecting the liver from severe depletion of adenine nucleotide.28,29... 

The same pathway is followed for D-fructose metabolism in liver, intestine, and kidney (see Scheme l).30-33 Phosphorylation of D-fruc-... 

Liver metabolizes up to 85% of orally administered D-fructose. Fructokinase, aldolase, and triose kinase are important control enzymes for hepatic D-fructose metabolism.62 The activities of these enzymes are subject to dietary composition and hormonal control. Total fructokinase, aldolase, and triose kinase decrease to about half or less of their normal activity on fasting for 48 to 72 hours, and are restored to normal in 24 hours upon D-fructose administration. Longterm feeding of D-fructose results in the maintenance of a considerably higher level of all three enzymes, an effect also seen with rats maintained on a high-fat or high-protein diet.62... 

The cell distribution of aldolase B corresponds with its proposed role in gluconeogenesis and D-fructose metabolism.339 Muscle aldolase B acts primarily on D-fructose 1,6-bisphosphate, whereas the aldolase from liver facilitates the cleavage of D-fructose 1,6-bisphosphate and D-fructose 1-phosphate at about equal rates. As a consequence,332,340 the metabolism of D-fructose by way of D-fructose 1-phosphate can readily occur in liver, where it is the primary, metabolic route. 

There are two genetic diseases associated with fructose metabolism. One is fructosuria, in which the liver enzyme, fructokinase, is missing. Thus, fructose is not metabolized but, instead, accumulates in the blood and is passed into... 

Fig. 29.3. Fructose metabolism. The pathway for the conversion of fructose to dihydroxy-acetone phosphate and glyceraldehyde 3-phosphate is shown in blue. These two compounds are intermediates of glycolysis and are converted in the liver principally to glucose, glycogen, or fatty acids. In the liver, aldolase B cleaves both fructose 1-phosphate in the pathway for fructose metabolism, and fructose 1,6-bisphosphate in the pathway for glycolysis.

In recent years it became apparent that fructose metabolism in the liver tissue has considerable effects on purine nucleotide metabolism. There is ample evidence that fructose metabolism is associated with acceleration of nucleotide degradation (1-5) and evidence is accumulating (6-8), indicating an acceleration effect of fructose also on purine synthesis. 

The mechanism responsible for the fructose-induced hyperuricemia in man has been unclear. In Figure 2 a schematic diagram summarizes some of the steps of fructose metabolism relevant to this discussion. In the liver, the phosphorylation of fructose to fructose-l-P utilizes the conversion of one ATP to ADP. Fructose-l-P... 

A monosaccharide obtained from dietary sources, either as the free sugar or as a part of the sucrose molecule. It is normally metabolized by the liver and kidney to glucose. Two inborn errors of fructose metabolism have been described ... 

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