Krebs cycle

Krebs Cycle (Citric acid cycle)

Series of 8 sequential reactions

Matrix of the mitorchondria

Synthesis of 2 ATP Generation of 8

energetic electrons

4 CO2 molecules

Krebs Cycle

Reaction 1: Condensation 2-carbon acetyl group from acetyl-

CoA Joins with oxaloacetate a four-

carbon molecule Forms a six-carbon molecule,

citrate.

Reaction 2: Isomerization Hydroxyl (-OH) group of citrate is

repositioned A water molecule is removed from one

carbon Water is added to another carbon on

the same citrate molecule. As a result, an –H group & an –OH group

change positions. Product is isocitrate-an isomer of

citrate

Reaction 3: The First Oxidation First energy yielding step of cycle Isocitrate undergoes an oxidative

decarboxylation reaction. First: isocitrate is oxidized Yielding a pair of electrons Associated with a proton as a

hydrogen atom Reduces NAD+ to NADH.

Reaction 3: The First Oxidation

Second: oxidized intermediate is decarboxylated

Central carbon atom splits off to form CO2

Yields a five-carbon molecule α-ketoglutarate

Reaction 4: The Second Oxidation α-ketoglutarate is decarboxylated Looses a CO2

CoEnzyme A is attached Forms succinyl-CoA Two electrons are extracted Associated with a proton as a hydrogen

atom Reduce another molecule of NAD+ to

NADH.

Reaction 5: Substrate-Level Phosphorylation Linkage between the four-carbon

succinyl group & CoA is a high-energy bond.

Bond is cleaved Energy released drives phosphorylation

of GDP, forming GTP. GTP is readily converted into ATP, Succinate 4-carbon fragment that

remains

Reaction 6: Third Oxidation

Succinate is oxidized to fumarate FAD+ is electron acceptor. FAD+ remains in a part of the inner

mitochondria membrane FADH2 (reduced) is used in

electron transport chain in the membrane

Reactions 7 & 8: Regeneration of Oxaloacetate. A water molecule is added to fumarate, Forms malate Malate is then oxidized Yields oxaloacetate a four-carbon

molecule Two electrons Associated with a proton as a hydrogen Reduce a molecule of NAD+ to NADH.

Reactions 7 & 8 : Regeneration of Oxaloacetate.

Oxaloacetate Molecule that began the cycle Combines with another two-carbon

acetyl group from acetyl-CoA Reinitiate the cycle.

Fig. 9-12-1

Acetyl CoA

Oxaloacetate

CoA—SH

1

Citrate

Citricacidcycle

Fig. 9-12-2

Acetyl CoA

Oxaloacetate

Citrate

CoA—SH

Citricacidcycle

1

2

H2O

Isocitrate

Fig. 9-12-3

Acetyl CoA

CoA—SH

Oxaloacetate

Citrate

H2O

Citricacidcycle

Isocitrate

1

2

3

NAD+

NADH

+ H+

-Keto-glutarate

CO2

Fig. 9-12-4

Acetyl CoA

CoA—SH

Oxaloacetate

Citrate

H2O

IsocitrateNAD+

NADH

+ H+

Citricacidcycle

-Keto-glutarate

CoA—SH

1

2

3

4

NAD+

NADH

+ H+SuccinylCoA

CO2

CO2

Fig. 9-12-5

Acetyl CoA

CoA—SH

Oxaloacetate

Citrate

H2O

IsocitrateNAD+

NADH

+ H+

CO2

Citricacidcycle

CoA—SH -Keto-

glutarate

CO2NAD+

NADH

+ H+SuccinylCoA

1

2

3

4

5

CoA—SH

GTP GDP

ADP

P iSuccinate

ATP

Fig. 9-12-6

Acetyl CoA

CoA—SH

Oxaloacetate

H2O

CitrateIsocitrate

NAD+

NADH

+ H+

CO2

Citricacidcycle

CoA—SH -Keto-

glutarate

CO2NAD+

NADH

+ H+

CoA—SH

P

SuccinylCoA

i

GTP GDP

ADP

ATP

Succinate

FAD

FADH2

Fumarate

1

2

3

4

5

6

Fig. 9-12-7

Acetyl CoA

CoA—SH

Oxaloacetate

Citrate

H2O

IsocitrateNAD+

NADH

+ H+

CO2

-Keto-glutarate

CoA—SH

NAD+

NADH

SuccinylCoA

CoA—SH

PP

GDPGTP

ADP

ATP

Succinate

FAD

FADH2

Fumarate

CitricacidcycleH2O

Malate

1

2

5

6

7

i

CO2

+ H+

3

4

Fig. 9-12-8

Acetyl CoA

CoA—SH

Citrate

H2O

IsocitrateNAD+

NADH

+ H+

CO2

-Keto-glutarate

CoA—SH

CO2NAD+

NADH

+ H+SuccinylCoA

CoA—SH

P i

GTP GDP

ADP

ATP

Succinate

FAD

FADH2

Fumarate

CitricacidcycleH2O

Malate

Oxaloacetate

NADH

+H+

NAD+

1

2

3

4

5

6

7

8

Krebs Cycle 2 pyruvate from glycolysis 6 CO2 molecules 2 ATP molecules 10 electron carriers 8 NADH molecules 2 FADH2

Figure 9.16b 2 FADH26 NADH

CITRICACID

CYCLE

PYRUVATEOXIDATION2 Acetyl CoA

+ 2 ATP

2 NADH

Glycolysis & the Krebs cycle

produced a large amount of electron carriers.

These carriers enter the electron transport chain

Help produce ATP

Electron transport chain Energy captured by NADH is not

harvested all at once. Transferred directly to oxygen 2 electrons carried by NADH are

passed along the electron transport chain if oxygen is present.

Oxidative phosphorylation Formation of ATP 1. Electron transport chain Series of molecules embedded in

the inner membranes of mitochondria.

Electrons are delivered at the top of the chain

Oxygen captures them at the bottom

Electron transport chain Large protein complexes Smaller mobile proteins Smaller lipid molecule called

ubiquinone (Q)

Fig. 9-13

NADH

NAD+2FADH2

2 FADMultiproteincomplexesFAD

Fe•S

FMN

Fe•S

Q

Fe•S

Cyt b

Cyt c1

Cyt c

Cyt a

Cyt a3

IV

Fre

e en

erg

y (G

) r e

lat i

ve t

o O

2 (

kcal

/mo

l)

50

40

30

20

10 2

(from NADHor FADH2)

0 2 H+ + 1/2 O2

H2O

e–

e–

e–

Electrons move towards a more electronegative carrier

Electrons move down an electron gradient

This flow of electron creates the active transport of protons out into the matrix

2. Chemiosmosis Protons diffuse back into the

matrix through a proton channel It is coupled to ATP synthesis

Electron transport chain Carbon monoxide & cyanide affect

the electron transport in the mitochondria

Shuts down the production of ATP Cell dies as does the organism

Fermentation Anaerobic conditions H atoms (NADH) are donated to

organic compounds Regenerates NAD+

Figure 9.17a2 ADP + 2 P i

NAD+

+ 2 H+

GLYCOLYSISGlucose

2 ATP

22

2 Ethanol 2 Acetaldehyde

2 Pyruvate

(a) Alcohol fermentation

2 CO2NADH

Figure 9.17b2 ADP + 2 P i

NAD+

+ 2 H+

GLYCOLYSISGlucose

2 ATP

22

Lactate

(b) Lactic acid fermentation

NADH

2 Pyruvate

2

Proteins and fats Other organic

molecules are an important source of energy.

Proteins First are broken down to amino

acids Each amino acid undergoes a

process called deamination. Removal of the nitrogen containing

side group After a series of reactions the

carbon groups enter the either glycolysis or the krebs cycle

Fats Fats are broken down to FA &

glycerol Each FA undergoes β oxidation Conversion of the FA to several

acetyl groups These groups combine with

coenzyme A to make acetyl-CoA

Regulation Control of the glucose catabolism Occurs at 3 key points 1. Control point in glycolysis Enzyme phosphofructokinase Catalyzes the conversion of

fructose 6-phosphate to fructose 1,6 bisphosphate.

Regulation High levels of ATP

inhibit phosphofructokinase

ADP & AMP activate the enzyme

Low levels of citrate also activate the enzyme

Regulation 2. Pyruvate dehydrogenase Enzyme that removes CO2 from

pyruvate. High levels of NADH will inhibit its

action

Regulation 3. High levels of ATP inhibit the

enzyme citrate synthetase Enzyme that starts the Krebs cycle Combines Acetyl-CoA with

oxaloacetate to make citrate

Evolution Krebs cycle & ETC function only in

aerobic conditions Glycolysis occurs in both Early bacteria used only glycolysis to

make ATP before O2

All kingdoms of life use glycolysis Occurs outside the mitochondria Indicates mitochondria developed later.