Online Microbiology Notes

Krebs (Citric Acid) Cycle Steps by Steps Explanation 4.68/5 (145)

SagarAryal November15,2015 Biochemistry 11Comments

Pleasefollowandlikeus:

Like

Share

8.1K

Tweet

13

Krebs (Citric Acid) Cycle Steps by Steps Explanation

ItisalsoknownasTriCarboxylicAcid(TCA)cycle.Inprokaryoticcells,thecitricacidcycleoccursinthe
cytoplasm;ineukaryoticcells,thecitricacidcycletakesplaceinthematrixofthemitochondria.
ThecyclewasfirstelucidatedbyscientistSirHansAdolfKrebs(1900to1981).HesharedtheNobel
PrizeforphysiologyandMedicinein1953withFritzAlbertLipmann,thefatherofATPcycle.
Theprocessoxidisesglucosederivatives,fattyacidsandaminoacidstocarbondioxide(CO2)througha
series of enzyme controlled steps. The purpose of the Krebs Cycle is to collect (eight) highenergy
electrons from these fuels by oxidising them, which are transported by activated carriers NADH and
FADH2 to the electron transport chain. The Krebs Cycle is also the source for the precursors of many
othermolecules,andisthereforeanamphibolicpathway(meaningitisbothanabolicandcatabolic).

The Net Equation

acetylCoA+3NAD+FAD+ADP+HPO42>2CO2+CoA+3NADH++FADH++ATP

Reaction 1: Formation of Citrate

The first reaction of the cycle is the condensation of acetylCoA with oxaloacetate to form citrate,
catalyzedbycitratesynthase.
OnceoxaloacetateisjoinedwithacetylCoA,awatermoleculeattackstheacetylleadingtotherelease
ofcoenzymeAfromthecomplex.

Reaction 2: Formation of Isocitrate

Thecitrateisrearrangedtoformanisomericform,isocitratebyanenzymeacontinase.
In this reaction, a water molecule is removed from the citric acid and then put back on in another
location.TheoveralleffectofthisconversionisthattheOHgroupismovedfromthe3tothe4position
onthemolecule.Thistransformationyieldsthemoleculeisocitrate.

Reaction 3: Oxidation of Isocitrate to -Ketoglutarate

In this step, isocitrate dehydrogenase catalyzes oxidative decarboxylation of isocitrate to form
ketoglutarate.
In the reaction, generation of NADH from NAD is seen. The enzyme isocitrate dehydrogenase
catalyzes the oxidation of the OH group at the 4 position of isocitrate to yield an intermediate which
thenhasacarbondioxidemoleculeremovedfromittoyieldalphaketoglutarate.

Reaction 4: Oxidation of -Ketoglutarate to Succinyl-CoA

Alphaketoglutarate is oxidized, carbon dioxide is removed, and coenzyme A is added to form the 4
carboncompoundsuccinylCoA.
Duringthisoxidation,NAD+isreducedtoNADH+H+.Theenzymethatcatalyzesthisreactionisalpha
ketoglutaratedehydrogenase.

Reaction 5: Conversion of Succinyl-CoA to Succinate

CoAisremovedfromsuccinylCoAtoproducesuccinate.
Theenergyreleasedisusedtomakeguanosinetriphosphate(GTP)fromguanosinediphosphate(GDP)
andPibysubstratelevelphosphorylation.GTPcanthenbeusedtomakeATP.Theenzymesuccinyl
CoAsynthasecatalyzesthisreactionofthecitricacidcycle.

Reaction 6: Oxidation of Succinate to Fumarate

Succinateisoxidizedtofumarate.
Duringthisoxidation,FADisreducedtoFADH2.Theenzymesuccinatedehydrogenasecatalyzesthe
removaloftwohydrogensfromsuccinate.

Reaction 7: Hydration of Fumarate to Malate

ThereversiblehydrationoffumaratetoLmalateiscatalyzedbyfumarase(fumaratehydratase).
Fumarase continues the rearrangement process by adding Hydrogen and Oxygen back into the
substratethathadbeenpreviouslyremoved.

Reaction 8: Oxidation of Malate to Oxaloacetate

Malate is oxidized to produce oxaloacetate, the starting compound of the citric acid cycle by malate
dehydrogenase.Duringthisoxidation,NAD+isreducedtoNADH+H+.

ATP Generation
TotalATP=12ATP
3NAD+=9ATP
1FAD=2ATP

1ATP=1ATP
Reviewing the whole process, the Krebs cycle primarily transforms the acetyl group and water, into
carbondioxideandenergizedformsoftheotherreactants.

Signicance ofKrebs Cycle

1.IntermediatecompoundsformedduringKrebscycleareusedforthesynthesisofbiomoleculeslike
aminoacids,nucleotides,chlorophyll,cytochromesandfatsetc.
2.IntermediatelikesuccinylCoAtakespartintheformationofchlorophyll.
3.AminoAcidsareformedfromKetoglutaricacid,pyruvicacidsandoxaloaceticacid.
4.Krebs cycle (citric Acid cycle) releases plenty of energy (ATP) required for various metabolic
activitiesofcell.
5.Bythiscycle,carbonskeletonaregot,whichareusedinprocessofgrowthandformaintainingthe
cells.

References
1.LehningerPrinciplesofBiochemistry.5thEdition.Chapter15:TheCitricAcidCycle.
2.ClackamasCommunityCollege.CitricAcidCycle.
3.Shmoop.CitricAcidCycle.
4.GaryE.Kaiser.CommunityCollegeofBaltimoreCounty.TheCitric(Krebs)AcidCycle.
5.UniversityofMichigan.KrebsCycle.
6.NewcastleUniversityTeachingServer.SchoolofBiomedicalSciencesWiki.Krebscycle.
7.SparkNotes.TheCitricAcidCycle.
8.JohnM.WyzAnt,Inc.TheKrebsCycle.
9.UniversityofCalifornia,Davis.ChemWiki.KrebsCycle.
10.BoundlessBiology.CitricAcidCycle.
11.ChemistryLearning.KrebsCycle.
12.KhanAcademy.Krebs/citricacidcycle.
13.TutorVista.Biology.CitricAcidCycle.
14.Study.com.TheCitricAcid(Krebs)Cycle:ProductsandSteps.
15.Wikipedia.CitricAcidCycle.

Krebs (Citric Acid) Cycle Steps by Steps Explanation

Please rate this note
Pleaseratethisnote

SubmitRating

(Visited23,582times,36visitstoday)

ShareThis:

The Author
Sagar Aryal
IamSagarAryal,apassionateMicrobiologistandtheScientificBlogger.IdidmyMaster'sDegreeinMedical
MicrobiologyandcurrentlyworkingasaTeachingAssistantatSt.Xavier'sCollege,Kathmandu,Nepal.Iam
particularlyinterestedinresearchrelatedtoMedicalMicrobiologyandVirology.FindmeonFacebook,Twitteror
Linkedin!!!