BIOCHEMISTRYANDMOLECULARBIOLOGYChapter 14Metabolism ofmonosaccharides anddisaccharidesDepartment of Biochemistry and Molecular Biology,Medicine School
Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY Metabolism of monosaccharides and disaccharides Chapter 14
山BIOCHEMISTRYANDMOLECULARBIOLOGYOverviewGlucose is the most commonmonosaccharideconsumed by humans, and its metabolism hasbeen discussed extensivelyDepartment of Biochemistry and Molecular Biology,Medicine School
Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY Glucose is the most common monosaccharide consumed by humans, and its metabolism has been discussed extensively. Overview
BIOCHEMISTRYANDMOLECULARBIOLOGYOverviewHowever, two other monosaccharides-fructose andgalactose-occur in significant amounts in the diet(primarily in disaccharides), and make importantcontributions to energy metabolism.Department of Biochemistry and Molecular Biology,Medicine School
Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY However, two other monosaccharides-fructose and galactose-occur in significant amounts in the diet (primarily in disaccharides), and make important contributions to energy metabolism. Overview
BIOCHEMISTRYANDMOLECULARBIOLOGYOverviewIn addition, galactose is an important componentof cell structural carbohydrates.Department of Biochemistry and Molecular Biology,Medicine School
Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY In addition, galactose is an important component of cell structural carbohydrates. Overview
3FRUCTOSEGLYCOLYSISMETABOLISMUnlesstheintrecellularBIOCHEMISTRYANDMOLECULARBIOLOGYconcentration of fructosebecomes unusually high,hexokinase is saturated withandphosphorylatesglucoseratherthanfructoseCH.OHCH.OH=0C=0HO-O-HC-HHO-H-C-OHH-C-OHH-C-OHH-C-OHCH.O-CH,OHHeonnese.7FructoseFructose6-phosphateFructose metabolismCATP-ATPFructokinasePnosproriucioknaseADPADPCH2O-PCHO-P0-0COHO-O-HHO-C-HH-C-OHH-C-OHH-C-OHH-C-OHCH,OHCH.O-PFructoseFructose1-phosphate1,6-bisphosphateAdpiaseA,BCAdoaseB00C-HO-HHH-C-OHH-C-OHH-C-OHC4OCHO-PCH.OHCH2O-PGlyceraldehydeGlyceraldehyde3-phosphateDihydroxyacetonephosphateFigure12.2nent of Biochemistry and Molecular Biology,Medicine SchoolPhosphorylationproductsoffructoseand their cleavage
Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY Fructose metabolism
HexokinaseGlucose 6-P GLYCOGENGLUCOSEGlucose6-mosphataseK1MOLECULARBIOLOGY￥Phosphoguo-GLUCONEOPIsomeraseGENESISySUCROSE+FRUCTOSESucraseFructose6-p人NESSENTIALFRUCTOSURIAATPRuchse1,6LackoffructokinasenispnosphatasePrucioiuinaseAutosomalrecessive(1:130.000Summary ofADPMbirths)Fructose1,6-bis-pBenign conditionFructose1-pfructoseFructose accumulates in the urineAldciaseAAldaiaseBDihydroxyacetonep★metabolismHEREDITARYFRUCTOSEINTOLERANCE(FRUCTOSEPOISONING)ATPGlyceraldehydeAutosomal recessive (1:20.000births)NADH+H+ThiosepAbsence of aldolase Bleads to intracellularIsomerasetrappingoffructose1-p.TrbsekhaseAicomofCauses severehypoglycemia,vomiting.denyurogenasejaundice,hemorrhage,hepatomegaly,renaldysfunction,hyperuricemia,andNAD+Ghyceraldehyde3-Placticacidemia才GlycerolFructose,sucrose,andsorbitolcancauseADPTHosePIsomerasehepatic failure and death.ATP-Therapy:RapiddetectionandremovalofDihydroxyacetonePfructoseandsucrosefromthedietGLYCOLYSISAGycenlkineseGycebipcerydingenaseADPKGlycerol-pPHOSPHOGLYCERIDESPYRUVATETRIACYLGLYCEROLS4Figure12.3Biology,Medicine SchoolSummaryoffructosemetabolism
Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY Summary of fructose metabolism
ASEMINALVESICLESGlycolysisA个个BIOCHEMISTRYANDMOLECULARBIOLOGYCHO-OHHOHH-OHH-OHBLOODCHCHGlucoseGlucoseNADPH+HAnosereducteseNADP+CH2OHOHSorbitolHOOHCLOHSorbitolmetabolism-NAD+SobitadenyuiogenaseYNADH+HOOH=0HO-0H--OHH-C-OHCHOHFructoseLENSNERVEBKIDNEYGlycolyaisABLOODGlucoseGlucose(elevated)NADPH+H-AuoseredcseNADP-SorbitolH20H.OH.oBiochemistry and Molecular Biology,MedicineSchoolFigure12.4Sorbitolmetabolism
Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY Sorbitol metabolism
GALACTOKINASEDERCIENCYCLASSICGALACTOSEMIARare autosomal recessivedisorderGalactose1-phosphate uridyltransferase(GALT)deficiency.NDMOLECULARBIOLOGYAutosomalrecessivedisorder(f:30.000births)Causes elevation ofgalactose inblood (galactosemia)andCausesgalactogemia andgalactosuria,vomiting.urine (galactosuria)diarhea,and jaundiceCauses galactitolaccumulafionAccumulationofgalactose1-phosphateandgalactitolifgalactose is present inthedietinnerve.lens.liverandkidneytissuecauseslivrElevatedgalactitol can cause cataracts.damageseverementalretardation,andcataractsPrenataldiagnosis ispossiblebychorionicvillusTreatment is dietary restrictionsampling.Newborn screening is availableMetabolism ofTherapy:Rapiddiagnosis and removalofGalactitol NADp+galactose (andthereforelactose)fromthe dietDespiteadequatetreatmentatriskfordevelopmentalgalactosedelays and,infemales,premature ovarianfailureNADPH+H+AidoseGlycogenieductaseGalactoknaseGALACTOSEGalactose1-PUDP-GlucosePPALDOSEREDUCTASEThe enzyme is present inADPATPGalactose 1-phospheteLOP-GiUcselivdyinaenundyiarsteasepyiophosproryiasetissue,seminalvesicles,andovaries.UDP-GALACTOSEK￥Glucose1-PLACTOSElt is physiologicallyunimportantUTEAVProsphogucomuta.sein galactosemetabolism unlessUDP-HEXOSEgalactose levels are high (as inLGlucose6-P4-enimerasegalactosemia).GLYCOLIPIDSGucose6-phosphatase(liver)￥ElevatedgalactitolcancauseNGLYCOPROTEINScataracts.UDP-GLUCOSEGLYCOLYSISGLUCOSEGLYCOSAMINOGLYCANSFigure12.5ilar Biology,MedicineSchoolMetabolismofgalactose
Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY Metabolism of galactose
B-o-Galactosyitransferase(proteinA)YANDMOLECULARBIOLOGY-Lactalbumin(proteinB)UDp-galactose.glucosegalactosyltransferase(Lactosesynthsse)LactosesynthesisuDp-galactoseUDPglucoseLBCtSECH.OHCH.OHOHa>HOHOHDHOHBGalactoseGlucoseFigure12.7olecularBiology,MedicineSchoolLactose synthesis
Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY Lactose synthesis
BIOCHEMISTRYANDMOLECULARBIOLOGYgalactoseThe other onosaccharideGalactosekinaseenter glycolysis1-P-galactoseGluATPmannoseADPHexoseG-6-P-1-P-glucosekinasemutasemutase6-P-mannoseF-6-PATP0HexoseADPfructosekinaseF-1,6-2PpyruvateDepartment of Biochemistryand Molecular Biology,MedicineSchool
Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY fructose Glu G-6-P F-6-P F-1,6-2P ATP ADP ATP ADP pyruvate galactose 1-P-galactose 1-P-glucose Galactose kinase mutase mannose 6-P -mannose Hexose kinase The other onosaccharide enter glycolysis