Carbohydrate metabolism

ADVANCED BIOCHEMISTRY Lecture (3 hours) Metabolism of other important carbohydrates: fructose, galactose and mannose Instructor: Dr Nguyen Thao Trang School of Biotechnology Semester I 2015-2016 Outlines •  Overview of glycolysis •  Metabolism of fructose •  Metabolism of galactose •  Metabolism of mannose Outlines •  Overview of glycolysis •  Metabolism of fructose •  Metabolism of galactose •  Metabolism of mannose Overview of glycolysis Biochemistry by Cambell and Farrell Overview of glycolysis •  Includes 10 reactions divided into stages: Stage (Preparation step): reactions 1-5 -  Glucose is phosphorylated, then converted to fructose which is again phosphorylated and cleaved into molecules of glyceraldehyde-3-phosphate - In this stage, ATP molecules are used Stage (Harvesting ATP): reactions 6-10 -  Two molecules of glyceraldehyde-3-phosphate are converted to pyruvate molecules -  In this stage, ATP and NADH molecules are produced ATP production = ATP produced – ATP used = - = Overall: Glucose → Pyruvate + ATP + NADH Biochemistry by Garrett and Grisham Overview of glycolysis •  Overall reaction of conversion of glucose in anaerobic condition: Glucose + 2NAD+ + 2ADP + 2Pi → Pyruvate + NADH + ATP +2 H2O + 4H+ , ΔG = - 96 kJ/mol Biochemistry, Tymoczko, Berge, Strayer Regulation of glycolysis •  Phosphofructose kinase (reaction 3) –  Is the most important control site in the mammalian glycolytic pathway –  The activity of the enzyme depends on the ATP/AMP ratio •  Hexosekinase (reaction 1) –  The inhibition of phosphofructokinase leads to the inhibition of hexokinase –  It is not the primary control site in glycolysis as glucose 6phosphate is not solely a glycolytic intermediate In muscle, glucose 6-phosphate can also be converted into glycogen The phosphorylation of fructose 6-phosphate to fructose 1,6bisphosphate is unique in glycolysis •  Pyruvate kinase (reaction 10) –  ATP allosterically inhibits pyruvate kinase to slow glycolysis when the energy charge is high Other substrates used in glycolysis Biochemistry by Garrett and Grisham Outlines •  Overview of glycolysis •  Metabolism of fructose •  Metabolism of galactose •  Metabolism of mannose 10 Metabolism of fructose in liver Fundamentals of biochemistry-Life at the molecular level, Voet, Voet, Pratt 13 Metabolism of fructose in liver •  The affinity of fructose-1-phosphate adolase for fructose-1-P is much poorer than that of fructose-1,6biphosphate, thus fructose-1-P accumulates in fructokinase-expressing tissues •  Thus, fructose-1-phosphate adolase is the rate-limiting enzyme for fructose metabolism 14 Metabolism of fructose in muscle •  Muscle which contains only hexokinase can phosphorylate fructose to fructose 6-phosphate which is a direct glycolytic intermediate •  However, hexokinase has a very low affinity to fructose compared to glucose, So it is not a significant pathway for fructose metabolism Unless it is present in very high concentration in blood Fundamentals of biochemistry-Life at the molecular level, Voet, Voet, Pratt 15 Is excess fructose harmful? •  Fructose is used as a sweetener in soft drinks and other foods gkdating.com http://www.ucsf.edu/news/2009/06/8187/obesity-andmetabolic-syndrome-driven-fructose-sugar-diet •  F r u c t o s e c a t a b o l i s m i n l i v e r b y p a s s e s t h e phosphofructokinase-catalyzed step of glycolysis and thereby avoids a major metabolic control point → Disrupt fuel metabolism so that glycolytic flux is directed toward lipid synthesis in the absence of a need for ATP production 16 Outlines •  Overview of glycolysis •  Metabolism of fructose •  Metabolism of galactose •  Metabolism of mannose 17 Metabolism of galactose •  The major source of galactose is lactose (a disaccharide of glucose and galactose) obtained from milk and milk products •  Galactose enters glycolysis by its conversion to glucose-1-phosphate (G1P) This occurs through a series of steps 18 Metabolism of galactose Fundamentals of biochemistry-Life at the molecular level, Voet, Voet, Pratt 19 Disease related to metabolism of galactose •  Galactosemia is a genetic disease characterized by the inability to convert galactose to glucose •  Symptoms: failure to thrive, mental retardation, and, in some instances, death from liver damage •  Galactosemia involve a deficiency in the enzyme catalyzing reaction of the interconversion, galactose-1phosphate uridylyl transferase → buildup of galatose in blood 20 Metabolism of galactose × Fundamentals of biochemistry-Life at the molecular level, Voet, Voet, Pratt 21 Disease related to metabolism of galactose •  Buildup of galatose in blood results in high concentration of galactose in the crystalline lens of the eye→ gatactose is reduced to gatatitol, presence of this sugar alcohol in the lens eventually causes cataract formation A healthy eye A eye with cataract Biochemistry, Tymoczko, Berge, Strayer 22 Disease related to metabolism of galactose •  Galactosemia is treated by a galactose-free diet •  Elimination of galactose from the diet prevents liver disease and cataract development •  The majority of patients still suffer from central nervous system malfunction, most commonly a delayed acquisition of language skills Female patients also display ovarian failure 23 Outlines •  Overview of glycolysis •  Metabolism of fructose •  Metabolism of galactose •  Metabolism of mannose 24 Metabolism of mannose •  Mannose, a product of digestion of polysaccharides and glycoproteins, is the C2 epimer of glucose: Fundamentals of biochemistry-Life at the molecular level, Voet, Voet, Pratt •  Mannose enters the glycolytic pathway after its conversion to fructose 6-phosphate via a two-reaction pathway 25 Metabolism of mannose •  Mannose enters the glycolytic pathway after its conversion to fructose 6-phosphate via a two-reaction pathway: 26 Artificial sweeteners Still wants to consume sugars (beverages, deserts) but not want to add any calorie? ARTIFICIAL SWEETENERS! networkoffood.com abqjournalfit.com Fundamentals of biochemistry-Life at the molecular level, Voet, Voet, Pratt Artificial sweeteners are compounds that mimic sugars but not metabolized or contribute a little to energy metabolism due to their low concentration Break down to aspatate; phenylalanine and methanol Instable to heat or be hydrolyzed in soft drinks over time Oldest artificial sweetener Sweet’n low Calorie-free Most popular artificial sweetener Equal and Nutrasweet 27 ... glycolysis •  Metabolism of fructose •  Metabolism of galactose •  Metabolism of mannose Outlines •  Overview of glycolysis •  Metabolism of fructose •  Metabolism of galactose •  Metabolism of... Garrett and Grisham Outlines •  Overview of glycolysis •  Metabolism of fructose •  Metabolism of galactose •  Metabolism of mannose 10 Metabolism of fructose •  Diets containing large amounts... ovarian failure 23 Outlines •  Overview of glycolysis •  Metabolism of fructose •  Metabolism of galactose •  Metabolism of mannose 24 Metabolism of mannose •  Mannose, a product of digestion