Fructose Metabolism

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Fructose Metabolism

    • Metabolism of fructose.
      • The major dietary source of fructose is the disaccharide sucrose in table sugar and fruit,.
      • Conversionoffructosetoglycolyticintermediates
        • Fructose is metabolized mainly in theliver
          • it is converted to pyruvate or, under fasting conditions, to glucose.
          • Fructoseisphosphorylatedby ATP toformfructose-1-phosphate.
            • The enzyme is fructokinase.(MCQ)
          • Fructose 1-phosphateis 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(MCQ)
          • glyceraldehydeis 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.(MCQ)
    • 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 2to 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 bypassphospho fructokinase-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(MCQ)
          • fructokinasedeficiency(MCQ)
          • abenign condition
        • Aldolase B deficiency (MCQ)
          • Hereditary fructose intolerance, HFI(MCQ)
          • 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. (MCQ)
          • As ATP falls, AMP rises.
          • In the absence of Pi, AMP is degraded, causing hyperuricemiaand lactic acidosis
        • The decreased availability of hepatic ATP
          • affects gluconeogenesis
            • causinghypoglycemia with vomiting
          • affectsprotein 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.(MCQ)
    • 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 somecells ,large amounts of glucose may enter these cells during times of hyperglycemia(MCQ)
      • Elevated intracellular glucose concentrations and an adequate supply of NADPH cause aldose reductase to produce a significant increase in the amount of sorbitol(MCQ)
      • 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.(MCQ)
      • 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(MCQ)

      Which one of the following is a non-reducing sugar:

      A.        Maltose          

      B.        Lactose

      C.        Sucrose           

      D.        Glucose

        

        Ans C. In sucrose the aldehyde group of a- glucose (Cj) is combined with keto group of p-fructose (C2) to form a glycosidic bond. It doesn’t contain any free aldehyde or ket.o group. These free groups are responsible for the reducing agents.

       

      Which carbohydrate is present in glycoproteins:

      A.        Arabinose       

      B.        Fructose

      C.        N-acetylneuraminic acid

      D.        Ribose

       

      ANS:   C. Glycoproteins are covalently bound to carbohydrates like galactose, mannose, N-acetyl galactosamine, N-acetyl glucosamine, xylose, L – fucose N- acetylneuraminic acid. Sialic acid is derived from neuraminic acid. Glycoproteins contain less than 4% of carbohydrates, whereas mucoproteins have more than 4% of carbohydrates.

       

      Which statement is incorrect regarding the structural features of monosaccharides required for active transport:

      A.        Carbon 2 should have a OH group

      B.        Pyranose ring should be present

      C.        Methyl or substituted methyl group should be present on carbon 5

      D.        Must have a keto group at C2

       

      ANS:   Keto group is present in fructose at C2, does not have OH group on C2 that’s why fructose is absorbed more slowly than glucose and galactose by active transport. The molecular configuration is necessary for active transport, which is mainly satisfied by gku< inland galactose.

      A 3-month-old girl is brought to the pediatrician due to fussiness and lethargy. According to the parents, the baby was just fine until the mother needed to return to work, and the baby was being switched from breast milk to baby foods, formula, and fruit juices. At that time, the child cried while feeding, sometimes vomited, and had been lethargic. The baby’s appetite seemed to have worsened. The parents thought that if only formula was used, the baby was better, but they really could not remember. Which possible enzyme defect might lead to this case presentation?

      (A)       Galactokinase

      (B)       Fructokinase

      (C)       Aldolase

      (D) Hexokinase

      (E)       Glucokinase

      7 The answer is C:

      Aldolase. The disorder is hereditary fructose intolerance, with a reduced ability to convert fructose-1-phosphate to dihydroxyacetone phosphate and glyceraldehyde. The specifi c defect is in aldolase B, with its activity reduced by as much as 85%. This problem is only evident when sucrose is introduced into the diet, and fructose enters the liver. The accumulation of fructose-1-phosphate, due to the reduced aldolase activity, leads to a constellation of physiological problems resulting in nausea, vomiting, and hypoglycemia. Elimination of fructose from the diet will reverse the symptoms. Galactokinase is needed for galactose metabolism; since the patient digests milk normally galactokinase activity is not altered. Similarly, glucose metabolism is not adversely affected (milk contains lactose, which is split into glucose and galactose), indicating that hexokinase and glucokinase activities are normal. The defect in aldolase B will hinder glycolysis, but the liver also contains aldolase C activity (this isozyme will not split fructose-1-phosphate), which enables glucose metabolism to be very close to normal. A deficiency in fructokinase will lead to an accumulation of fructose (not fructose-1-phosphate), which is released into the urine (fructosuria), but does not lead to the physiological symptoms exhibited by the patient. The fructose pathway (indicating the reaction catalyzed by aldolase B), and its relationship to glycolysis, is shown below.

       

      A 3-month-old infant, when switched to a formula diet plus fruit juices, begins to vomit and displays severe hypoglycemia after eating. Removal of the fruit juices from the diet seemed to reduce the severity of the symptoms. At the pediatrician’s office, an inborn error of metabolism was considered, which could explain the hypoglycemia. Which explanation is most likely?

      (A)       Fructose inhibition of the debranching enzyme

      (B)       Galactose-1-phosphate inhibition of glycogen phosphorylase

      (C)       Fructose-1-phosphate inhibition of glycogen phosphorylase

      (D)       Fructose-6-phosphate inhibition of glycogen phosphorylase

      (E)       Galactose inhibition of aldolase

      3 The answer is C:

      Fructose-1-phosphate inhibition of glycogen phosphorylase. The child has hereditary fructose intolerance, a defect in aldolase B activity in the liver. This leads to an accumulation of fructose-1-phosphate in the liver (and, as fructokinase has a high Vmax, a large amount of fructose-1-phosphate accumulates). At high levels, fructose-1-phosphate, through similarity in structure to glucose-1-phosphate, inhibits glycogen phosphorylase activity, leading to hypoglycemia (glycogen degradation is inhibited when blood glucose levels drop). The fructose is derived from the fruit juices introduced to the child’s diet. Fructose does not inhibit debranching enzyme, and fructose-6-phosphate has no effect on glycogen phosphorylase (recall, one of the products of the glycogen phosphorylase reaction is glucose-1-phosphate, not glucose-6-phosphate). Galactose is found in lactose, which, while present in milk, is not found in fruit juice.



      Fructose Metabolism Basics
      This video will cover the basics of fructose metabolism
      Biochemistry Help: Fructose Metabolism
      In this video, we discuss the concepts behind Fructose metabolism, via the use of Fructokinase as the main enzyme behind conversion of Fructose into the phosphorylated and thus metabolically active form Fructose 1-Phosphate. It is then cleaved by Aldolase B into component Trioses which can be used in a variety of different reaction pathways.
      Metabolic differences between Glucose and Fructose
      The Metabolic differences between Glucose and Fructose

      Dr. Barry Sears is a leading authority on the impact of the diet on hormonal response, genetic expression, and inflammation. A former research scientist at the Boston University School of Medicine and the Massachusetts Institute of Technology, Dr. Sears has dedicated his research efforts over the past 30 years to the study of lipids. He has published more than 30 scientific articles and holds 13 U.S. patents in the areas of intravenous drug delivery systems and hormonal regulation for the treatment of cardiovascular disease. He has also written 13 books, including the New York Times #1 best-seller “The Zone”. These books have sold more than 5 million copies in the U.S. and have been translated into 22 different languages.
      Disorders of Fructose Metabolism
      I describe the two disorders of Fructose Metabolism: Essential Fructosuria and Fructose Intolerance,
      Fructose metabolism