Glycolysis and Clinical Implications PDF

BIOENERGETICS AND INTEGRATED METABOLISM (BIOC202) How do other monossacharides enter the glycolytic pathway?  GALACTOSEMIA – clinical implication Galactose enter glycolysis as per below reaction Deficiency of Galactokinase or Galactose-1-phosphat...

BIOENERGETICS AND INTEGRATED METABOLISM (BIOC202) How do other monossacharides enter the glycolytic pathway?  GALACTOSEMIA – clinical implication Galactose enter glycolysis as per below reaction Deficiency of Galactokinase or Galactose-1-phosphate uridyltransferase GLYCOLYSIS  GALACTOSEMIA A deficiency of galactose-1-phosphate uridyltransferase manifests itself in the newborn as intolerance of breast or cow’s milk which contains lactose. Galactose-1-phosphate rises in the blood and causes damage to the liver, kidneys, brain, intestine and spleen.  Lactose Intolerance - implications maltase Maltose + H2O D-Glucose + D-Glucose lactase Lactose + H2O D-Galactose + D-Glucose Sucrose + H2O sucrase D-Fructose + D-Glucose Galactose Glucose-6-phosphate Mannose Fructose-6-phosphate Fructose (muscle) Fructose-6-phosphate Fructose (liver) Glyceraldehyde-3-phosphate  GALACTOSE METABOLISM AND GALACTOSEMIA When galactose accumulates, the reaction catalyzed by aldose reductase becomes very active: Aldose reductase which has a high Km for aldoses  Km is the Michaelis constant and represents the substrate concentration at which the reaction rate is half the maximum rate of the reaction i.e. high levels of aldoses (galactose) are required for the enzyme to become active therefore aldose reductase is not normally active The accumulation of galactitol and depletion of NADPH in the lens of the eye, leads to damage of the tissue and to cataract.  FRUCTOSE METABOLISM Fructose enters the glycolytic pathway by one of two routes. In muscle: Hexokinase, which phosphorylates various monosaccharides, can also act on fructose to produce fructose 6-phosphate. But this is not the major pathway. Hexokinase has low affinity (high Km) for fructose. As affinity of the enzyme hexokinase for fructose is very low, hence this is a minor pathway  FRUCTOSE METABOLISM In the liver, we have a major pathway for phosphorylation of fructose – catalysed by the enzyme fructokinase ( also been identified in kidney and intestine) Fructose is mostly phosphorylated by fructokinase to fructose 1-phosphate – this enzyme phosphorylates fructose only and will not phosphorylate glucose. Fructose 1-phosphate is cleaved to glyceraldehyde and dihydroxyacetone phosphate (DHAP) by aldolase B.  FRUCTOSE INTOLERANCE A metabolic defect can occur which involves fructose-1-phosphate aldolase B and leads to fructose (sucrose) intolerance in the newborn. Fructose-1-phosphate accumulates in the liver and damages it, resulting in jaundice. High concentrations of fructose-1-phosphate also inhibit: aldolase of the glycolytic pathway (reaction 4) thus inhibiting ATP generation & glycogen phosphorylase leading to hypoglycemia. SUCROSE INTOLERANCE