FRUCTOSE METABOLISM | Anatomy2Medicine
fructose-metabolism

FRUCTOSE METABOLISM

    • Metabolism of fructose.
      • The major dietary source of fructose is the disaccharide sucrose in table sugar and fruit,.
      • Conversion of fructose to glycolytic intermediates
        • Fructose is metabolized mainly in the liver
          • it is converted to pyruvate or, under fasting conditions, to glucose.
          • Fructose is phosphorylated by ATP to form fructose-1-phosphate.
            • The enzyme is fructokinase.

 

  • Fructose 1-phosphate is cleaved to form dihydroxyacetone phosphate (DHAP) and glyceraldehyde
  • Enzyme : aldolase B

 

            • Aldolase B is the same liver enzyme that cleaves fructose 1,6-bisphosphate in glycolysis
          • glyceraldehyde is phosphorylated by ATP to form glyceraldehyde 3-phosphate. DHAP and glyceraldehyde 3-phosphate are intermediates of glycolysis.
        • In tissues other than liver, the major fate of fructose is phosphorylation by hexokinase to form fructose 6-phosphate, which enters glycolysis
          • Hexokinase has an affinity for fructose about 5% of that for glucose.
      • Production of fructose from glucose

 

  • Glucose is reduced to sorbitol

 

          • Enzyme : aldose reductase, which reduces the aldehyde group to an alcohol
        • Sorbitol is then reoxidized at carbon 2 to form fructose
          • Enzyme :  sorbitol dehydrogenase

 

  • Kinetics of fructose metabolism

 

        • Why is the rate of fructose metabolism is more rapid than that of glucose ?
        • Because the trioses formed from fructose 1-phosphate bypass phosphofructokinase-1—the major rate-limiting step in glycolysis

 

  • Disorders of fructose metabolism

 

      • Deficiency of the key enzymes required for the entry of fructose into intermediary metabolic pathways

 

  • Essential fructosuria

 

          • fructokinase deficiency

 

  • a benign condition

 

          • Aldolase B deficiency
        • Hereditary fructose intolerance, HFI

 

  • causes a severe disturbance of liver and kidney metabolism

 

          • The first symptoms of HFI appear when a baby is weaned from milk and begins to be fed food containing sucrose or fructose.
          • Fructose 1-phosphate accumulates, resulting in a drop in the level of inorganic phosphate (Pi)  therefore, of ATP.
          • As ATP falls, AMP rises.
          • In the absence of Pi, AMP is degraded, causing hyperuricemia and lactic acidosis,
          • The decreased availability of hepatic ATP
            • affects gluconeogenesis

 

  • causing hypoglycemia with vomiting

 

            • affects protein synthesis
              • causing a decrease in blood clotting factors and other essential proteins
          • Kidney function may also be affected.

 

  • Diagnosis of HFI can be made on the basis of

 

            • fructose in the urine
            • enzyme assay or by DNA-based tesTing
          • With HFI, sucrose and sorbitol (a sugar alcohol), as well as fructose, must be removed from the diet to prevent liver failure and possible death. Individuals with HFI display an aversion to sweets and, consequently, have an absence of dental caries.

 

  • Conversion of mannose to fructose 6-phosphate

 

  • Mannose
    • C-2 epimer of glucose
    • is an important component of glycoproteins
  • Hexokinase phosphorylates mannose, producing mannose 6-phosphate,
  • mannose 6-phosphate, is (reversibly) isomerized to fructose 6-phosphate
    • Enzyme : phospho- mannose isomerase.
  • There is little mannose in dietary carbohydrates
    • Most intracellular mannose is synthesized from fructose
    • preexisting mannose produced by the degradation of structural carbohydrates and salvaged by hexokinase

 

  • The effect of hyperglycemia on sorbitol metabolism:

 

  • Because insulin is not required for the entry of glucose into some cells
  • large amounts of glucose may enter these cells during times of hyperglycemia
  • Elevated intracellular glucose concentrations and an adequate supply of NADPH cause aldose reductase to produce a significant increase in the amount of sorbitol
  • sorbitol cannot pass efficiently through cell membranes and, therefore, remains trapped inside the cell
  • This is exacerbated when sorbitol dehydrogenase is low or absent, for example, in retina, lens, kidney, and nerve cells.
  • As a result, sorbitol accumulates in these cells, causing strong osmotic effects and, therefore, cell swelling as a result of water retention
  • It leads to  cataract formation, peripheral neuropathy, and microvascular problems leading to nephropathy and retinopathy