Fructose metabolism in liver

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

Pharmacokinetics Fructose Fructose is slowly absorbed from the Gl tract. Metabolized in liver by phosphorylation and partly converted to liver glycogen and glucose. Excreted in urine. Dextrose Dextrose is rapidly absorbed from Gl tract. Distributed and stored throughout tissues. Metabolized in liver to carbon dioxide and water. 

Mechanism of Action A polyalcoholic sugar with osmotic cathartic actions. Specific mechanism unknown. Therapeutic Effect Catharsis, urinary irrigation. Pharmacokinetics Onset of action within 15-60 minutes. Poorly absorbed by both oral and rectal route. Metabolized in liver to primary metabolite, fructose. 

F15. Frohman, C. E., and Orten, J. M., Tracer studies of acids of the tricarboxylic acid cycle II. Effect of fructose and bicarbonate on acetate metabolism in liver of diabetic rats. J. Biol. Chem. 220, 315 (1956). 

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. 

Figure 20-5. Metabolism of fructose. Aldolase A is found in all tissues, whereas aldolase B is the predominant form in liver. (, not found in liver.)...

Fructose-1,6-bisphosphatase deficiency, first describ ed by Baker and Winegrad in 1970, has now been reported in approximately 30 cases. It is more common in women and is inherited as an autosomal recessive disorder. Initial manifestations are not strikingly dissimilar from those of glucose-6-phosphatase deficiency. Neonatal hypoglycemia is a common presenting feature, associated with profound metabolic acidosis, irritability or coma, apneic spells, dyspnea, tachycardia, hypotonia and moderate hepatomegaly. Lactate, alanine, uric acid and ketone bodies are elevated in the blood and urine [11]. The enzyme is deficient in liver, kidney, jejunum and leukocytes. Muscle fructose-1,6-bisphosphatase activity is normal. 

Fructose is found in honey and fruit and as part of the disaccharide sucrose (common table sugar). Sucrose is hydrolyzed by intestinal brush border sucrase, and the resulting monosaccharides, glucose and fructose, are absorbed into the portal blood. The liver phosphorylates frurtose and cleaves it into glyceraldehyde and DHAP. Smaller amounts are metabolized in renal proximal tubules. The pathway is shown in Figure 1-12-7 important enzymes to remember are ... 

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.]... 

Fructose can be metabolized by two routes. In adipose tissue and muscle, hexokinase can phosphorylate fructose to fructose 6-phosphate that then enters glycolysis. In liver, most of the enzyme present is glucokinase not hexokinase and this does not phosphorylate fructose. In this tissue, fructose is metabolized instead by the fructose 1-phosphate pathway. 

Fructose is an abundant sugar in the human diet sucrose (table sugar) is a disaccharide which when hydrolyzed yields fructose and glucose (see Topic Jl) and fructose is also a major sugar in fruits and honey. There are two pathways for the metabolism of fructose one occurs in muscle and adipose tissue, the other in liver. 

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

Metabolic mutant. What are the likely consequences of a genetic disorder rendering fructose 1,6-bisphosphatase in liver less sensitive to regulation by fructose 2,6-bisphosphate ... 

The initial metabolism of fructt>se tends to occur in liver, not in muscle. The opposite situation holds for glucose. The study reported in Table 4.8, involving human subjects, compares the metabolism of glucose with that of fructose. Fasting... 

Sorbitol is widely used in a number of pharmaceutical products and occurs naturally in many edible fruits and berries. It is absorbed more slowly from the gastrointestinal tract than sucrose and is metabolized in the liver to fructose and glucose. Its caloric value is approximately 16.7J/g (4cal/g). Sorbitol is better tolerated by diabetics than sucrose and is widely used in many sugar-free liquid vehicles. However, it is not considered to be unconditionally safe for diabetics. 

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