Oxidative pentose phosphate pathway

It covers the UG CBCS syllabus of Sem VI Botany Honors students. However, it is suitable for both UG and PG students.

1. OXIDATIVE PENTOSE
PHOSPHATE PATHWAY
DR. RIMI ROY
J.K.COLLEGE
PURULIA

2. •Thepentosephosphatepathway-alsocalledthephosphogluconate
pathwayandthehexosemonophosphateshunt
•Itisametabolicpathwayparalleltoglycolysis.
•ItgeneratesNADPHandpentoses(5-carbonsugars)aswellasribose5-
phosphate,aprecursorforthesynthesisofNucleotides.
•Whilethepentosephosphatepathwaydoesinvolveoxidationofglucose,
itsprimaryroleisanabolicratherthancatabolic.
•Thispathwayappearstohaveaveryancientevolutionaryorigin.The
reactionsofthispathwayaremostlyenzyme-catalyzedinmoderncells,
however,theyalsooccurnon-enzymaticallyunderconditionsthatreplicate
thoseoftheArcheanocean,andarecatalyzedbymetalions,particularly
ferrousions(Fe(II)).Thissuggeststhattheoriginsofthepathwaycould
datebacktotheprebioticworld
INTRODUCTION

3. •Therearetwodistinctphasesinthepathway:
•Oxidativephase:
•Thefirstistheoxidativephase,inwhichNADPHisgenerated
•Non-oxidativephase:
•thesecondisthenon-oxidativesynthesisof5-carbonsugars.
•Formostorganisms,thepentosephosphatepathwaytakesplacein
thecytosol
•Inplants,moststepstakeplaceinplastids

4. Phases
•Oxidativephase
•Inthisphase,twomoleculesofNADP
+
arereducedto
NADPH,utilizingtheenergyfromtheconversionofglucose-
6-phosphateintoribulose5-phosphate
•Theoverallreactionforthisprocessis:
•Glucose6-phosphate+2NADP
+
+H
2O→ribulose5-
phosphate+2NADPH+2H
+
+CO
2

5. Reactants Products Enzyme Description
Glucose 6-phosphate +
NADP+
→ 6-phosphoglucono-δ-
lactone + NADPH
glucose 6-phosphate
dehydrogenase
Dehydrogenation. The
hydroxyl on carbon 1 of
glucose 6-phosphate
turns into a carbonyl,
generating a lactone,
and, in the process,
NADPH is generated.
6-phosphoglucono-δ-
lactone + H
2O
→ 6-phosphogluconate
+ H
+
6-
phosphogluconolactona
se
Hydrolysis
6-phosphogluconate +
NADP
+
→ ribulose 5-phosphate
+ NADPH+ CO
2
6-phosphogluconate
dehydrogenase
Oxidative
decarboxylation. NADP
+
is the electron acceptor,
generating another
molecule of NADPH, a
CO
2, and ribulose 5-
phosphate.
The entire set of reactions can be summarized as follows:

7. •Non-oxidativephase
•Duringthenon-oxidativephase,3moleculesofribulose5-phosphate
gothroughaseriesofreactionstobeconvertedtoFructose6-
phosphateandglyceraldehyde3phosphate.
•Thenon-oxidativephasesusemultipleenzymes,twoofwhichare
exclusivetothispathway.Thosearetransketolaseandtransaldolase.
Theothersareenzymesalsousedingluconeogeneticorglycolytic
pathways.
•Transketolaseandtransaldolasebothfunctionbybasicallymoving
groupsofH–C–OHbetweensugarmolecules.Transketolaseuses
TPPasacofactorandtransaldolasedoesn’t.
•Sometissuesdon’tneedNADPH,andjustneedspentoses.Theycan
producepentoseswithoutNADPHthroughotherpathways.

8. Reactants Products Enzymes
ribulose 5-phosphate → ribose 5-phosphate
Ribose-5-phosphate
isomerase
ribulose 5-phosphate → xylulose 5-phosphate
Ribulose 5-Phosphate 3-
Epimerase
xylulose 5-phosphate + ribose
5-phosphate
→ glyceraldehyde 3-phosphate +
sedoheptulose7-phosphate
transketolase
sedoheptulose7-phosphate +
glyceraldehyde 3-phosphate
→ erythrose 4-phosphate +
fructose 6-phosphate
transaldolase
xylulose 5-phosphate +
erythrose 4-phosphate
→ glyceraldehyde 3-phosphate +
fructose 6-phosphate
transketolase

9. e
e
e
e e
e
e
e
e

10. Net reaction:
3 ribulose-5-phosphate
1 ribose-5-phosphate + 2 xylulose-5-phosphate
2 fructose-6-phosphate + glyceraldehyde-3-phosphate

11. Significance of PPP:
•Thegenerationofreducingequivalents,intheformofNADPH,usedinreductive
biosynthesisreactionswithincells(e.g.fattyacidsynthesis).
•Productionofribose5-phosphate(R5P),usedinthesynthesisofnucleotidesand
nucleicacids.
•Productionoferythrose4-phosphate(E4P)usedinthesynthesisofaromatic
aminoacids.
•Aromaticaminoacids,inturn,areprecursorsformanybiosyntheticpathways,
includingthelignininwood.
•OneoftheusesofNADPHinthecellistopreventoxidativestress.Itreduces
glutathioneviaglutathionereductase,whichconvertsreactiveH
2O
2intoH
2Oby
glutathioneperoxidase.Ifabsent,theH
2O
2wouldbeconvertedtohydroxylfree
radicals,whichcanattackthecell.Erythrocytes,forexample,generatealarge
amountofNADPHthroughthepentosephosphatepathwaytouseinthe
reductionofglutathione.

12. Source: https://themedicalbiochemistrypage.org

13. Significance of PPP:
•ThePPPistheonlypathwaythatallowsplantstoutilizesugarssuch
asD-xylose,D-ribose,L-arabinose,whichcannotbecatabolizedby
otherroutes.
•AlthoughthebasicfeaturesoftheoxPPParewellestablished,details
ofhowthepathwayoperatesinplantsandhowitinfluencesother
processesremainquestionable.

14. Regulation:
•Glucose-6-phosphatedehydrogenaseistherate-controllingenzymeofthis
pathway.
•ItisallostericallystimulatedbyNADP
+
andstronglyinhibitedbyNADPH
•TheratioofNADPH:NADP
+
isnormallyabout100:1inlivercytosoland
othercases.
•Thismakesthecytosolahighly-reducingenvironment.AnNADPH-utilizing
pathwayformsNADP
+
,whichstimulatesGlucose-6-phosphate
dehydrogenasetoproducemoreNADPH.
•G6PDactivityisalsopost-translationallyregulatedbycytoplasmic
deacetylaseSIRT2

15. Source: Lindsay E Wu & David A Sinclair.SIRT2 and the pentose phosphate shunt
The EMBO Journal Vol 33 | No 12 | 2014

16. IMPORTANT FACTS:
Glucose-6-phosphate dehydrogenase deficiency
•ItisanX-linkedrecessivedisorderthatresultsindefectiveglucose-6-
phosphatedehydrogenaseenzyme
•Redbloodcellbreakdownmaybetriggeredbyinfections,certain
medication,stress,orfoodssuchasfavabeans
•Followingaspecifictrigger,symptomssuchasyellowishskin,dark
urine,shortnessofbreath,andfeelingtiredmaydevelop
•Complicationscanincludeanemiaandnewbornjaundice

17. THANK YOU