Hexose MetabolismAldoses and KetosesMutarotation of GlucoseMutarotation of FructoseCommon HexosesSources of SugarsFructose MetabolismSucrose (Table Sugar)All TissuesCleavage of Sucrose (a-glucosidase or invertase)Slide 11Muscle Metabolism of Fructose (Anaerobic Glycolysis) Large Amounts of HexokinaseLiver Metabolism of Fructose I (Little Hexokinase)Liver Metabolism of Fructose IIMechanism of Aldolase (Formation of Schiff Base)Mechanism of Aldolase (Aldol Cleavage Reaction)Mechanism of Aldolase (Formation of Dihydroxyacetone-P)Liver Metabolism of Fructose IIIComplexity of Liver MetabolismFructose IntoleranceGalactose MetabolismLactose Metabolism (Dairy Products)Mutarotation of b-D-GalactoseGlycolytic Enzymes are specific and do not recognize galactose!Need EpimerizationPhosphorylation of GalactoseActivation of GalactoseEpimerization of UDP-GalactoseMechanism of EpimerizationWhy UDP-Galactose?Formation of Glucose-1-PFormation of Glucose-6-PGalactosemia (Mental Retardation and Death)CataractsMannose MetabolismPhosphorylation of MannoseIsomerization of Mannose-6-PMechanism of IsomerizationHexose MetabolismAldoses and KetosesCCOHCOHHHHOCCOHHCH2OHOHHCH2OHCCCCCH2OHOHHOOHHOHHD-glucoseD-f ructoseMutarotation of GlucoseHHHOOHCOCCH2OHO HO HHOHHOOCH2OHO HOHO ROHHOOCH2OHO HOHCHHO HO HCOH O HCH2OHCCH O HCH....or+[+18.7°][+112.2°]anomericcarbonatomβ-D-glucoseα-D-glucoseMutarotation of FructoseHOCH2OHCH2OHOHHOOCH2OHCH OHCH2OHCHO HCH OHC OHOCH2CH2OHOHOHHOOD-Fructoseβ-D-Fructoseα-D-FructoseCommon HexosesOCH2OHHHOHOHHHOHHOHOCH2OHHOHHOHHHOHHOHOCH2OHHHOHOHHOHHHOHOOHCH2OHHHOH HCH2OHOHa-D-Glucose a-D-Galactose a-D-Mannosea-D-FructoseSources of Sugars•Glucose: lactose (dairy products) and sucrose (table sugar)•Fructose: fruits and sucrose•Galactose: lactose•Mannose: polysaccharides and glycoproteinsFructose MetabolismSucrose(Table Sugar)O--D-Glucopyranosyl-(1—> 2)--D-FructofuranosideOOCH2OHHHOHHOOHHHOHH HOCH2HOH HHCH2OHOAll TissuesSucroseα-D-glucose + β-D-f ructosea-Glucosidase(I nvertase)GlycolysisMutarotationα-D-f ruct oseCleavage of Sucrose(-glucosidase or invertase)OOCH2OHHHOHHOOHHHOHH HOCH2HOH HHCH2OHOH2OOCH2OHHHHOOHHHOHHOHOHOHOCH2HOH HHCH2OHHGlucose FructoseMutarotation of FructoseHOCH2OHCH2OHHOHHOHOCH2OHCOH OHCH2OHCHO HCH OHCHOCH2HCH2OHOHHOHHOHOD-Fructoseβ-D-Fructoseα-D-FructoseMuscle Metabolism of Fructose(Anaerobic Glycolysis)Large Amounts of HexokinaseOHOHOCH2HOH HCH2OHOHHATP ADPOHOPOCH2HOH HCH2OHOHHHexokinaseα-D-FructoseGlycolysisFructose-6-PLiver Metabolism of Fructose I(Little Hexokinase)OHOHOCH2HOH HCH2OHOHHATP ADPOHOHOCH2HOH HCH2OPOHHFructokinaseα-D-Fructose(Committed Step)Fructose-1-PLiver Metabolism of Fructose IICH2OPCCCCCH2OHOHHOOHHH OHGlycolysisCHOCHOHCH2OHGlyceraldehydeOHOHOCH2HOH HCH2OPOHHDHAPCH2OPCCH2OHOFructose-1-PFruct ose-1-P AldolaseMechanism of Aldolase(Formation of Schiff Base)H2COPCCCCCH2OHNHHHOOHHOHHEnzyme+H2COPCCCCCH2OHOHHOOHHOHH+H3N EnzymeH2OMechanism of Aldolase(Aldol Cleavage Reaction)HHH2COPCCCCCH2OHNHHOOHOHHEnzymeCH2OPCCNHEnzymeHHO:CHOCHOHCH2OH:B+Mechanism of Aldolase(Formation of Dihydroxyacetone-P)CH2OPCCNHHHOEnzyme:H2OCH2OPCCH2OHOH2N–EnzymeLiver Metabolism of Fructose IIICHOCHOHCH2OHATPADPCHOCHOHCH2OPNAD+CH2OHCHOHCH2OHNAD+CH2OHCCH2OPOCH2OHCHOHCH2OPGlyceraldehydeGlyceraldehyde KinaseGlyceraldehyde-3-PGlycolysisAlcoholDehydrogenaseNADH + H+GlycerolGlycerolKinaseGlycerol-3-PDihydroxyacetone-P(DHAP)NADH + H+Glycerol-PDehydrogenaseTriose-PIsomeraseComplexity of Liver MetabolismBreakdown of Many MetabolitesFructose Intolerance•Too Much Fructose–Fructose-1-P Aldolase is rate-limiting–Depletion of Pi–Reduction in [ATP]–Increase in glycolysis–Accumulation of lactate (acid) in blood•Fructose-1-P Aldolase Deficiency (Genetic Disease)Galactose MetabolismLactose Metabolism(Dairy Products)GlycolysisOOCH2OHHHOHOHHHOHHOCH2OHHOHHHOHHOHOCH2OHHHOHOHHHOHOHHLactoseGlucoseβ-D-Galactoseβ-GalactosidaseMutarotation of -D-GalactoseGlycolytic Enzymes are specific and do not recognize galactose!Need EpimerizationOCH2OHHHOHOHHHOHHOHOCH2OHHHHOOHHHOHHOHGlucoseGalactoseEpimerizationPhosphorylation of GalactoseOCH2OHHOHHOHHHOHHOHATP ADPOCH2OHHOHHOHHHOHHOPO3=GalactokinaseGalactose Galactose-1-PActivation of GalactoseOCH2OHHOHHOHHHOHHOPO3=OCH2OHHHOHOHHHOHHO P OOO–P OO–OUridineOCH2OHHOHHOHHHOHHO P OOO–P OO–OUridineUMPGalactose-1-PGalactose-1-PUridylyl TransferaseUDP-GlucoseGlucose-1-PUDP-GalactoseGlucose-6-PPhosphoglucomutaseGlycolysisEpimerization of UDP-GalactoseOCH2OHHOHHOHHHOHHO P UMPOO–[NAD+]OCH2OHHHOHOHHHOHHO P UMPOO–UDP-Galactose-4-EpimeraseUDP-GlucoseUDP-GalactoseMechanism of EpimerizationOCCH2OHHOHHHOHHO P UMPOO–OWhy UDP-Galactose?GlycoproteinsGlycolipids(Require UDP-Galactose)Formation of Glucose-1-POCH2OHHHOHOHHHOHHO P UMPOO–PPiUTPOCH2OHHHOHOHHHOHHO P O–OO–UDP-GlucosePyrophosphorylaseUDP-GlucoseGlucose-1-PFormation of Glucose-6-POCH2OHHHOHOHHHOHHO P O–OO–OCH2OPO32–HHOHOHHHOHHOHPhosphoglucomutaseGlucose-6-PGlucose-1-PGlucose-6-P ——> GlycolysisGalactosemia(Mental Retardation and Death)TreatmentGalactose-free diet(reversal of all symptoms except mental retardation)CataractsCCCOHHOHHHOC HHOC OHHCH2OHCH2OHCCOHHHHOC HHOC OHHCH2OHNAD(P)H NAD(P)+Galactose GalactitolMannose MetabolismPhosphorylation of MannoseOCH2OHHHOHOHHHOHHOHATP ADPOCH2OPHHOHOHHHOHHOHα-D-MannoseHexokinaseMannose-6-PIsomerization of Mannose-6-POCH2OPHHOHOHHHOHHOHOHOPOCH2HHOH HCH2OHOHPhosphomannoseIsomeraseFructose-6-PMannose-6-PMechanism of IsomerizationH CCHOO HRAldoseCCH OO HRBH +CCH OORBH HH CHOC ORHKetoseB :B :