Minorpathwaysof

Minor
pathways of
carbohydratesmetabolism
y
Dr.AtifHassanKhirelsied
FacultyofMedicine
InternationalUniversityofAfrica,Khartoum,Sudan
y
,
,

Contents
FructoseMetabolism
g
ClinicalSignificancesofFructoseMetabolism
GalactoseMetabolism
Clinical Significances of Galactose Metabolism
ClinicalSignificancesofGalactoseMetabolism
MannoseMetabolism
GlucuronateMetabolism
ClinicalSignificancesofGlucuronate

Fructosemetabolism
Dietscontainlargeamountsofsucrose.
Humanscanutilizefructoseasasourceofenergy.
Thepathwaysoffructosemetabolismdifferin
p
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muscleandliver.

Fructosemetabolism
Musclesusehexokinase tophosphorylate fructose
toF6P(glycolytic intermediate).
Theliverusesfructokinase
The liver uses fructokinase togenerateF1P.
to generate F 1 P
Inlivertheformofaldolase BcanutilizebothF1,6BP
andF1Passubstrates.
Aldolase BsplitsF1PtoDHAP
B splits F 1 P to DHAP andglyceraldehyde.
and glyceraldehyde

Fructosemetabolism
TheDHAPisconverted,bytriose phosphate
isomerase to G3P and enters glycolysis
isomerase,toG3Pandentersglycolysis.
Theglyceraldehyde canbephosphorylatedtoG3P
byglyceraldehyde
ygy
y kinaseorconvertedtoDHAPby
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actionsofalcoholdehydrogenase,glycerolkinase
and glycerol phosphate dehydrogenase
andglycerolphosphatedehydrogenase.

Entryoffructoseintotheglycolytic pathwayin
hepatocytes.
hepatocytes.

Clinicalsignificancesoffructosemetabolism
Essentialfructosuria isabenignmetabolicdisorder
g
causedbythelackoffructokinase.
Fructosuria ofthisdiseasedependsonthetime
andamountoffructoseandsucroseintake.

Clinicalsignificancesoffructosemetabolism
Hereditaryfructoseintolerance
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Isapotentiallylethaldisorderresultingfromalackof
aldolase B.
B.
Th
Thedisorderischaracterizedbyseverehypoglycemia
di d i h
t i db
h
l
i
andvomitingfollowingfructoseintake.
Prolongedintakeoffructoseleadstovomiting,poor
feeding,jaundice,hepatomegaly,hemorrhageand
eventuallyhepaticfailureanddeath.

Clinicalsignificancesoffructosemetabolism
Hereditaryfructoseintolerance
Thehypoglycemiaiscausedbyaccumulationof
fructose1phosphateanddepletionofinorganic
p p
p
g
phosphatethusinhibitionofglycogenolysis.
Thesequestrationofinorganicphosphatealsoleadsto
depletion of ATP and hyperuricemia
depletionofATPandhyperuricemia.
Patientsremainasymptomaticonadietdevoidof
fructoseandsucrose.

Galactosemetabolism

GalactoseMetabolism
Galactose
Galactose,entersglycolysisbyitsconversiontoglucose
enters glycolysis by its conversion to glucose
1phosphate(G1P).
Thisoccursthroughaseriesofsteps.
Firstthegalactoseisphosphorylatedbygalactokinase
togalactose1phosphate(Gal1P).
Epimerization
EpimerizationofGal1PrequiresthetransferofUDP
of Gal1P requires the transfer of UDP
fromUDPglucosebygalactose1phosphateuridyl
transferase togenerateUDP
to generate UDPgal
galandG
and G1P
1 P.

Galactosedegradation

Galactosesynthesis

Galactosemetabolism
TheUDPgalactose isepimerizedtoUDPglucoseby
UDPgalactose4epimerase.
The
TheUDPportionisexchangedforphosphate
UDP portion is exchanged for phosphate
generatingglucose1phosphatewhichthenis
converted to G6P
convertedtoG
6 Pbyphosphoglucose
by phosphoglucose mutase.
mutase.

ClinicalSignificancesofgalactoseMetabolism
Galactosemia isamajorsymptomofthreeenzyme
is a major symptom of three enzyme
defects.
1. Deficiencyofthegalactose1phosphateuridyl
transferase.
transferase
2 Deficiencyofthegalactokinase.
2.
D fi i
f th
l t ki
3 DeficiencyofUDPgalactose4epimerase.
3.
D fi i
f UDP l
4 i

ClinicalSignificancesofgalactoseMetabolism
Clinicalfindingsofthesegalactosemia include:
1. Impairedliverfunction
p
2. Elevatedbloodgalactose.
g
3. Metabolicacidosis.
1. Urinarygalactitol
Urinary galactitol excretion andhyperaminoaciduria.
and hyperaminoaciduria.
2. Blindness isduetotheconversionofcirculating
is due to the conversion of circulating
galactose tothesugaralcoholgalacitol

ClinicalSignificancesofgalactosemetabolism
Lactose intolerance
Lactoseintolerance
Adefectscausedbydeficiencyoflactase.
Vomitinganddiarrheaoccurfollowingingestionof
milk,henceindividualsaretermedlactose
ilk h
i di id l
dl
intolerant.

MannoseMetabolism
Thedigestionofmanypolysaccharidesand
glycoproteins yieldsmannosewhichis
phosphorylatedbyhexokinase togenerate
mannose6phosphate.

MannoseMetabolism
Mannose6phosphateisconvertedtofructose6
h h
d f
phosphate, by the enzyme phosphomannose
phosphate,bytheenzymephosphomannose
isomerase,andthenenterstheglycolytic pathway

orisconvertedtoglucose6phosphatebythe
i
d
l
h h
b h
gluconeogenic pathwayofhepatocytes.
pathway of hepatocytes.

GlucuronateMetabolism
Glucuronate
Glucuronateisahighlypolarmoleculewhichis
is a highly polar molecule which is
incorporatedintoproteoglycans aswellascombining
with bilirubin andsteroidhormones;
withbilirubin
and steroid hormones;
It
Itcanalsobecombinedwithcertaindrugstoincrease
can also be combined with certain drugs to increase
theirsolubility.
Glucuronateisderivedfromglucoseintheuronic
acid pathway
acidpathway.

GlucuronateMetabolism
Theuronic
h
acidpathwayisutilizedtosynthesize
d
h
l d
h
glucuronate andLascorbate.
Thepathwayinvolvestheoxidationofglucosae6
p
y
g
phosphatetoUDPglucuronate.
UDPglucuronate isusedinthesynthesisof
glycosaminoglycan andproteoglycans
and proteoglycans aswellas
as well as
formingcomplexeswithbilirubin,steroids andcertain
drugs.
drugs

ClinicalSignificanceofGlucuronate
Aninabilitytoconjugatebilirubin,forinstancein
hepaticdiseaseorwhenthelevelofbilirubin
p
productionexceedsthecapacityoftheliver,isa
contributorycauseofjaundice.
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