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The Citric Acid Cycle: A Detailed Breakdown of Its Stages and Products, Lecture notes of Chemistry

A detailed explanation of the citric acid cycle, also known as the krebs cycle. It outlines the eight steps of this metabolic process, the reactants and products of each step, and the enzymes involved. The document also explains how the cycle contributes to atp synthesis by producing nadh and fadh2.

What you will learn

  • What are the reactants and products of each step in the Citric Acid Cycle?
  • How does the Citric Acid Cycle contribute to ATP synthesis?
  • Which enzymes catalyze the reactions in the Citric Acid Cycle?

Typology: Lecture notes

2021/2022

Uploaded on 09/12/2022

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bg1
Step1
CC
CH3
O
O
O-
CCH3
O
CoA
CO2
NAD+ NADH CoA
C
C
CH2
C
O
O-
O
O
O-Oxaloacetate (4C) Citrate(6C)
CoA
C
C
CH2
C
O
O-
O
O-
CH2
OH C
O
O-
C
C
CH
C
O
O-
O
O-
CH2C
O
O-
OH
H
Isocitrate (6C)
NAD+
NADH
Step2
C
CH2
CH2
C
O
O-
O
CO
O-
CO2
Step3
α‐Ketoglutarate (5C)
C
CH2
CH2
C
O
O-
O
CoA
C
CH2
CH2
C
O
O-
O
O-
C
CH
O
O-
CH
CO
O-
C
CH
CH2
C
O
O-
O
O-
OH
NAD+
NADH
CoA
CO2
Step4
Succinyl CoA (4C)
GTP GDP
CoA
ATP
ADP
Pi
Succinate (4C)
FADH2
FAD
Step5
Furmate (4C)
Step6
H2O
Malate (4C)
Step7
NAD+
NADH
Step8
ThefigureaboverepresentstheCitricAcidCycle(alsocalledthe“KrebsCycle”).Thepartofthemoleculethatbecomescarbon
dioxideishighlightedinabluebox.Noticethata4carbonmoleculecalledOxaloacetatepicksup2morecarbonswhenitisjoined
withanacetylgroupfromAcetylCoA.Throughthebeginningstepsofthecycle,2carbonsarelostascarbondioxideandthe
moleculeisagainrestoredtoa4carbonstate,readytopickupanotheracetylgroup.
Thedetailsoftheeightstepsaboveareshowninthefollowingpages.Thistime,thepartofthemoleculethatundergoesachange
ishighlightedinblueandthenameoftheenzymethatcatalyzesthereactionisinagreenbox.
CitricAcidCycle
pf3

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Step 1

C C CH 3

O O

O -

C CH 3

O CO (^2) CoA

NAD+ NADH CoA

C C CH 2 C

O

O -

O

O O - Oxaloacetate (4C) Citrate (6C)

CoA

C C CH 2 C

O

O -

O O -

HO CH 2 C O

O -

C C CH C

O

O -

O O -

CH 2 C O

O - HO

H

Isocitrate (6C)

NAD+

NADH

Step 2

C CH 2 CH 2 C

O

O -

O C O O -

CO 2

Step 3

α‐Ketoglutarate (5C)

C

CH 2

CH 2

C

O

O -

O

CoA

C

CH 2

CH 2

C

O

O -

O

O -

C

CH

O

O -

CH

C O

O -

C

HC

CH 2

C

O

O -

O

O -

OH

NAD+

NADH

CoA

CO 2

Step 4

Succinyl CoA (4C)

CoA GTP GDP

ATP

ADP

Pi

Succinate (4C)

FADH

FAD

Step 5

Furmate (4C)

Step 6

H 2 O

Malate (4C)

Step 7

NAD+

NADH

Step 8

The figure above represents the Citric Acid Cycle (also called the “Krebs Cycle”). The part of the molecule that becomes carbon

dioxide is highlighted in a blue box. Notice that a 4 carbon molecule called Oxaloacetate picks up 2 more carbons when it is joined

with an acetyl group from Acetyl CoA. Through the beginning steps of the cycle, 2 carbons are lost as carbon dioxide and the

molecule is again restored to a 4 carbon state, ready to pick up another acetyl group.

The details of the eight steps above are shown in the following pages. This time, the part of the molecule that undergoes a change

is highlighted in blue and the name of the enzyme that catalyzes the reaction is in a green box.

Citric Acid Cycle

Step 1

Step 2

The CH 3 end of the acetyl CoA loses a proton and becomes bonded to the second carbonyl carbon (C=O) of oxyloacetate. The coenzyme (CoA) is subsequently lost with the input of water.

Citrate

Synthase

Acetyl CoA Oxaloacetate

An isomerization reaction takes place. This involves the removal of a water molecule and then the insertion of a water molecule. The hydroxyl (OH) group changes position to a different carbon as a result. isocitrate

Step 3

This is the first of 4 oxidation steps in the cycle. The carbon carrying the hydroxyl group (OH) is converted to a carbonyl group (C=O). CO2 is lost from the intermediate and alpha ketoglutarate is produced. NADH is produced.

Isocitrate

deyhdrogenase

GDP

Step 4

Another oxidation step that results in another loss of CO2. This reaction is very complex and is similar to the reaction that converts pyruvate to acetly CoA. NADH is produced.

Step 5

CoA is displaced when an inorganic phosphate replaces CoA. Then the phosphate is used to phosphorylate GDP to make GTP. Later the high energy phosphate on GTP can be used to phosphorylate ADP to make ATP.

citrate

Aconitase

Isocitrate

α –Ketoglutarate dehydrogenase

Succinyl‐CoA

GTP Succinate

C CH 3

O CoA

C C CH 2 C

O

O -

O

O O -

CoA

H 2 O

S‐Citryl‐CoA intermediate Citrate

C C CH 2 C

O

O-

O O -

HO CH 2 C O

CoA

C

C

CH 2

C

O

O -

O

O -

HO CH 2 C

O

O -

C C CH C

O

O -

O O -

HO CH 2 C O

O - H

C C CH C

O

O -

O O -

CH 2 C O

O - HO

H

C C

O

O -

CH 2 C O

O - C C O O -

H

H 2 O H 2 O

Cis‐aconitate intermediate

C C CH C

O

O -

O O -

CH 2 C O

O - HO

H

CO 2

C

C

C

C

O

O -

O

O -

CH 2 C

O

H O^ -

O

C CH 2 CH 2 C

O

O -

O C O NAD+ NADH O - Oxylosuccinate intermediate (^) α‐Ketoglutarate

C CH 2 CH 2 C

O

O -

O C O O - α‐Ketoglutarate

+ CoA

C

CH 2

CH 2

C

O

O -

O

CoA

CO 2

NAD+ NADH

Pi

C

CH 2

CH 2

C

O

O -

O

CoA Succinyl‐CoA

C

CH 2

CH 2

C

O

O -

O

O -

+ CoA

H 2 O

Step 6

In this, the third oxidation reaction, two hydrogens are removed from succinate. FAD+ becomes reduced to FADH2.

Succinate Furmate

ATP

ADP

Succinyl ‐ CoA‐ synthase

C Succinate dehydrogenase

C

C

C

O

O -

O

O -

H H

H H

C C

O

O -

C C O O -

H H

FAD FADH