Minor pathways ofMinorpathwaysofcarbohydratesmetabolismy

Dr.AtifHassanKhirelsied

FacultyofMedicineInternationalUniversityofAfrica,Khartoum,Sudany , ,

ContentsFructoseMetabolism

ClinicalSignificancesofFructoseMetabolismg

GalactoseMetabolism

Clinical Significances of Galactose MetabolismClinicalSignificancesofGalactoseMetabolism

MannoseMetabolism

GlucuronateMetabolism

ClinicalSignificancesofGlucuronate

Fructosemetabolism

Dietscontainlargeamountsofsucrose.

Humanscanutilizefructoseasasourceofenergy.

Thepathwaysoffructosemetabolismdifferinp ymuscleandliver.

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.

Fructosemetabolism

TheDHAPisconverted,bytriose phosphateisomerase to G3P and enters glycolysisisomerase,toG3Pandentersglycolysis.

Theglyceraldehyde canbephosphorylatedtoG3Pbyglyceraldehyde kinaseorconvertedtoDHAPbyy g y y yactionsofalcoholdehydrogenase,glycerolkinaseand glycerol phosphate dehydrogenaseandglycerolphosphatedehydrogenase.

Entryoffructoseintotheglycolytic pathwayinhepatocytes.hepatocytes.

Clinicalsignificancesoffructosemetabolism

Essentialfructosuria isabenignmetabolicdisordergcausedbythelackoffructokinase.

Fructosuria ofthisdiseasedependsonthetimeandamountoffructoseandsucroseintake.

Clinicalsignificancesoffructosemetabolism

Hereditaryfructoseintolerancey

Isapotentiallylethaldisorderresultingfromalackofaldolase B.aldolase B.

Th di d i h t i d b h l i Thedisorderischaracterizedbyseverehypoglycemiaandvomitingfollowingfructoseintake.

Prolongedintakeoffructoseleadstovomiting,poorfeeding,jaundice,hepatomegaly,hemorrhageandeventuallyhepaticfailureanddeath.

Clinicalsignificancesoffructosemetabolism

Hereditaryfructoseintolerance

Thehypoglycemiaiscausedbyaccumulationoffructose1phosphateanddepletionofinorganicp p p gphosphatethusinhibitionofglycogenolysis.

Thesequestrationofinorganicphosphatealsoleadstodepletion of ATP and hyperuricemiadepletionofATPandhyperuricemia.

Patientsremainasymptomaticonadietdevoidoffructoseandsucrose.

Galactosemetabolism

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.

Galactosedegradation

Galactosesynthesis

Galactosemetabolism

TheUDPgalactose isepimerizedtoUDPglucosebyUDPgalactose4epimerase.

The UDP portion is exchanged for phosphateTheUDPportionisexchangedforphosphategeneratingglucose1phosphatewhichthenisconverted to G6P by phosphoglucose mutase.convertedtoG 6 Pbyphosphoglucose mutase.

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.

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

ClinicalSignificancesofgalactosemetabolism

Lactose intoleranceLactoseintolerance

Adefectscausedbydeficiencyoflactase.

Vomitinganddiarrheaoccurfollowingingestionofilk h i di id l d lmilk,henceindividualsaretermedlactose

intolerant.

MannoseMetabolism

Thedigestionofmanypolysaccharidesand

glycoproteins yieldsmannosewhichis

phosphorylatedbyhexokinase togenerate

mannose6phosphate.

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.

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.

GlucuronateMetabolism

h d h l d h Theuronic acidpathwayisutilizedtosynthesizeglucuronate andLascorbate.

Thepathwayinvolvestheoxidationofglucosae6p y gphosphatetoUDPglucuronate.

UDPglucuronate isusedinthesynthesisofglycosaminoglycan and proteoglycans as well asglycosaminoglycan andproteoglycans aswellasformingcomplexeswithbilirubin,steroids andcertaindrugsdrugs.

ClinicalSignificanceofGlucuronate

Aninabilitytoconjugatebilirubin,forinstanceinhepaticdiseaseorwhenthelevelofbilirubinpproductionexceedsthecapacityoftheliver,isacontributorycauseofjaundice.y j