biochem lecture for 2nd year M B B S.Fructose & Galactose metabolism
Galactose and Ftuctose Metabolism K
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Transcript of Galactose and Ftuctose Metabolism K
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Minor pathways ofMinorpathwaysofcarbohydratesmetabolismy
Dr.AtifHassanKhirelsied
FacultyofMedicineInternationalUniversityofAfrica,Khartoum,Sudany , ,
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ContentsFructoseMetabolism
ClinicalSignificancesofFructoseMetabolismg
GalactoseMetabolism
Clinical Significances of Galactose MetabolismClinicalSignificancesofGalactoseMetabolism
MannoseMetabolism
GlucuronateMetabolism
ClinicalSignificancesofGlucuronate
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Fructosemetabolism
Dietscontainlargeamountsofsucrose.
Humanscanutilizefructoseasasourceofenergy.
Thepathwaysoffructosemetabolismdifferinp ymuscleandliver.
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Fructosemetabolism
Musclesusehexokinase tophosphorylate fructosetoF6P(glycolytic intermediate).
The liver uses fructokinase to generate F 1 P Theliverusesfructokinase togenerateF1P.
Inlivertheformofaldolase BcanutilizebothF1,6BPandF1Passubstrates.
Aldolase B splits F 1 P to DHAP and glyceraldehyde Aldolase BsplitsF1PtoDHAP andglyceraldehyde.
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Fructosemetabolism
TheDHAPisconverted,bytriose phosphateisomerase to G3P and enters glycolysisisomerase,toG3Pandentersglycolysis.
Theglyceraldehyde canbephosphorylatedtoG3Pbyglyceraldehyde kinaseorconvertedtoDHAPbyy g y y yactionsofalcoholdehydrogenase,glycerolkinaseand glycerol phosphate dehydrogenaseandglycerolphosphatedehydrogenase.
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Entryoffructoseintotheglycolytic pathwayinhepatocytes.hepatocytes.
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Clinicalsignificancesoffructosemetabolism
Essentialfructosuria isabenignmetabolicdisordergcausedbythelackoffructokinase.
Fructosuria ofthisdiseasedependsonthetimeandamountoffructoseandsucroseintake.
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Clinicalsignificancesoffructosemetabolism
Hereditaryfructoseintolerancey
Isapotentiallylethaldisorderresultingfromalackofaldolase B.aldolase B.
Th di d i h t i d b h l i Thedisorderischaracterizedbyseverehypoglycemiaandvomitingfollowingfructoseintake.
Prolongedintakeoffructoseleadstovomiting,poorfeeding,jaundice,hepatomegaly,hemorrhageandeventuallyhepaticfailureanddeath.
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Clinicalsignificancesoffructosemetabolism
Hereditaryfructoseintolerance
Thehypoglycemiaiscausedbyaccumulationoffructose1phosphateanddepletionofinorganicp p p gphosphatethusinhibitionofglycogenolysis.
Thesequestrationofinorganicphosphatealsoleadstodepletion of ATP and hyperuricemiadepletionofATPandhyperuricemia.
Patientsremainasymptomaticonadietdevoidoffructoseandsucrose.
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Galactosemetabolism
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GalactoseMetabolism
Galactose enters glycolysis by its conversion to glucose Galactose,entersglycolysisbyitsconversiontoglucose1phosphate(G1P).
Thisoccursthroughaseriesofsteps. Firstthegalactoseisphosphorylatedbygalactokinasetogalactose1phosphate(Gal1P).
Epimerization of Gal1P requires the transfer of UDPEpimerizationofGal1PrequiresthetransferofUDPfromUDPglucosebygalactose1phosphateuridyltransferase to generate UDPgal and G1Ptransferase togenerateUDP galandG 1 P.
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Galactosedegradation
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Galactosesynthesis
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Galactosemetabolism
TheUDPgalactose isepimerizedtoUDPglucosebyUDPgalactose4epimerase.
The UDP portion is exchanged for phosphateTheUDPportionisexchangedforphosphategeneratingglucose1phosphatewhichthenisconverted to G6P by phosphoglucose mutase.convertedtoG 6 Pbyphosphoglucose mutase.
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ClinicalSignificancesofgalactoseMetabolism
Galactosemia is a major symptom of three enzyme Galactosemia isamajorsymptomofthreeenzymedefects.
1. Deficiencyofthegalactose1phosphateuridyltransferasetransferase.
2 D fi i f th l t ki2. Deficiencyofthegalactokinase.
3 D fi i f UDP l 4 i3. DeficiencyofUDPgalactose4epimerase.
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ClinicalSignificancesofgalactoseMetabolism
Clinicalfindingsofthesegalactosemia include:
1. Impairedliverfunctionp
2. Elevatedbloodgalactose.g
3. Metabolicacidosis.
1. Urinary galactitol excretion and hyperaminoaciduria.1. Urinarygalactitol excretion andhyperaminoaciduria.
2. Blindness is due to the conversion of circulating2. Blindness isduetotheconversionofcirculatinggalactose tothesugaralcoholgalacitol
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ClinicalSignificancesofgalactosemetabolism
Lactose intoleranceLactoseintolerance
Adefectscausedbydeficiencyoflactase.
Vomitinganddiarrheaoccurfollowingingestionofilk h i di id l d lmilk,henceindividualsaretermedlactose
intolerant.
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MannoseMetabolism
Thedigestionofmanypolysaccharidesand
glycoproteins yieldsmannosewhichis
phosphorylatedbyhexokinase togenerate
mannose6phosphate.
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MannoseMetabolism
h h d f Mannose6phosphateisconvertedtofructose6
phosphate, by the enzyme phosphomannosephosphate,bytheenzymephosphomannose
isomerase,andthenenterstheglycolytic pathway
i d l h h b h orisconvertedtoglucose6phosphatebythe
gluconeogenic pathway of hepatocytes.gluconeogenic pathwayofhepatocytes.
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GlucuronateMetabolism
Glucuronate is a highly polar molecule which is Glucuronateisahighlypolarmoleculewhichisincorporatedintoproteoglycans aswellascombiningwith bilirubin and steroid hormones;withbilirubin andsteroidhormones;
It can also be combined with certain drugs to increase Itcanalsobecombinedwithcertaindrugstoincreasetheirsolubility.
Glucuronateisderivedfromglucoseintheuronicacid pathwayacidpathway.
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GlucuronateMetabolism
h d h l d h Theuronic acidpathwayisutilizedtosynthesizeglucuronate andLascorbate.
Thepathwayinvolvestheoxidationofglucosae6p y gphosphatetoUDPglucuronate.
UDPglucuronate isusedinthesynthesisofglycosaminoglycan and proteoglycans as well asglycosaminoglycan andproteoglycans aswellasformingcomplexeswithbilirubin,steroids andcertaindrugsdrugs.
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ClinicalSignificanceofGlucuronate
Aninabilitytoconjugatebilirubin,forinstanceinhepaticdiseaseorwhenthelevelofbilirubinpproductionexceedsthecapacityoftheliver,isacontributorycauseofjaundice.y j