22-1

Principles and Applications ofInorganic, Organic, and Biological

ChemistryDenniston, Topping, and Caret

4th ed

Chapter 22

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Power Point to Accompany

22-2

22.1 The Mitochondria

Size of a bacterial cell.

Outer mitochondrial membrane.

Inner mitochondrial membrane:

Highly folded membranes=christae

Has electron transport system and ATP synthase

Space between membranes is the intermembrane space.

Interior is the matrix

22-3

22.2 Pyruvate to Acetyl CoA

Pyruvate from glycolysis enters the mitochondria and is converted to acetyl CoA which activates the acetyl group for entry into the tricarboxylic acid cycle (Kreb’s cycle or TCA cycle).

Pyruvate to acetyl CoA

Decarboxylation (loss of CO2)

Oxidation by NAD+ which accepts the hydride anion.

Acetyl group linked to coenzyme A via a thioester bond.

22-4

Pyruvate Decarboxylate Complex

pyruvate

Acetyl CoA

VitaminsThiamine PP (B1)

FAD (B2)

NAD+ (niacin)CoA (panthothenic acid)+ coenzyme lipoamide

CH3CO

COO-

CH3CO

S CoA

CoA-SH

NAD+CO2

NADH + H+

TPP, FADMg2+, lipoic acid

22-5

22.3 Overview: Aerobic RespirationOxygen-requiring breakdown of food and

production of ATP.

Enzymes in the mitochondrial matrix.

Three oxidations transfer hydride to NAD+ or FAD.

Electrons passed from NAD+ or FAD to the electron transport chain and then O2.

Protons are transferred to the intermembrane space which leads to the synthesis of ATP as protons return to the matrix.

22-6

22.4 The Citric Acid CycleAcetyl CoA and oxaloacetate feed the citric

acid (TCA) cycle.The acetyl group is oxidized to two molecules

of CO2 and high energy electrons are transferred to NAD+ and FAD.

CH3 C

O

S O P

O

O

O

O P

O

O

O

NCCH

C

N

NC

CH

N

NH2

P

O

O

OO

CH2

HH

OH

HH

CH2C

CH3

CH3

C

OH

H

C

O

NCH2CH2C

O

NCH2CH2

H H

Acetyl CoA

22-7

TCA Cycle

SCoACH3CO

CH2CH2C

COO-

COO-

O

CO2

NAD+

CoA-SH

CH2COHCH2

COO-

COO-

COO-

CH2CHC

COO-

COO-

COO-

OH H

CO2

CH2CH2C

COO-

OS-CoA

NAD+

CH2

C O

COO-

COO-

NAD+

CH2CH2

COO-

COO-

GTP Pi

C

-OOC

COO-H

H

FAD

H2O

CH2

C

COO-

COO-

OH H

Nowrecycle

22-8

The TCA Cycle-1, 2

Citratesynthase

CH2

C

COO-

COO-

O

SCoACH3CO H2O

CH2COHCH2

COO-

COO-

COO-+HSCoA+ H+

Citrate

aconitase

COH

CH2CH

COO-

COO-

COO-

H

Isocitrate

22-9

The TCA Cycle-3, 4

Isocitrate

isocitrate dehydrogenaseCH2

CC

COO-

COO-

COO-

O HH

H+ NAD+

-ketoglutarate

+ CO2

+ NADH

CH2CH2C

COO-

COO-

O1. Oxidation: ROH to C=O2. Carbon dioxide released3. NAD+ reduced

CH2CH2C

COO-

COO-

O

+ NAD+

+ CoA

-ketoglutarate dehydrogenase complex

CH2CH2C

COO-

OS CoA

+ CO2

+ NADH

Succinyl CoA

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The TCA Cycle-5, 6

+ GDP + Pi

succinyl-CoA synthase

Succinyl CoA

CH2CH2C

COO-

OS CoA

+ GTP+ CoA

Succinate

CH2CH2COO

-

COO-

CH2CH2COO

-

COO-

+ FAD

succinate dehydrogenase

C

C

-OOC

COO-

H

H

Fumarate+ FADH2

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The TCA Cycle-7, 8

+ H2Ofumarase

C

C

-OOC

COO-H

H L-Malate

CC

COO-

COO-

OH HH H

CH2

C

COO-

COO-

O

malate dehydrogenase

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22.5 Control of the TCA Cycle

Insert Fig 22.6 to fill below line

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22.6 Oxidative PhosphorylationThe respiratory electron transport system is

made up of a series of electron carriers embeded in the inner mitochondrial membrane.

At three sites in the electron transport system, protons (H+) can be pumped from the matrix to the intermembrane space.

NADH provides three ATP molecules

FADH2 provides two ATP molecules

because only two sites are involved.

ATP synthesis occurs at the ATP synthase.

22-14

Insert Fig 22.7 4th edI want to add comments after the

Figure is in.

22-15

ATP Synthase and ATPThe terminal electron acceptor in the

transport chain is dioxygen.

½ O2 + 2 H+ H2O

The protons in the intermembrane space flow back through ATP synthase F0 channel

activating F1 that catalyzes phosphorylation

of ADP to produce ATP.

22-16

Energy Yield from One GlucoseGlycolysis

Substrate-level phosphorylation 2 ATP

2 NADH X 2 ATP (cytoplasm) 4 ATP

Two Pyruvate to two Ac-CoA

2 NADH X 3 ATP/NADH 6 ATP

Citric Acid Cycle (Two turns)

2 GTP X 1 ATP/GTP 2 ATP

6 NADH X 3 ATP/NADH 18 ATP

2 FADH2 X 2 ATP/FADH2 4 ATP

NET 36 ATP

22-17

22.7 Degradaton of Amino AcidsWhen the body has depleted glycogen

(starving), it can use amino acids for fuel.

Degredation takes place in the liver in two stages.

1. Removal of the amino group.

2. Degradation of the carbon skeleton.

22-18

Degradaton of Amino Acids, cont.Removal of the a-amino group: Transamination

Requires pyridoxal phosphate, a coenzyme derived from vitamin B6.

-ketoglutarateaspartate

CH2

CH2

C

COO-

COO-

O

CH2

CH

COO-

NH3

+

COO-+

CH2

CH2

CH

COO-

COO-

NH3

+

CH2

C

COO-

OCOO

-+

oxaloacetate glutamate

transaminase

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Degradaton of Amino Acids, cont.Oxidative Deamination

glutamate

CH2

CH2

CH

COO-

COO-

NH3

+

+ NAD+

+ H2O CH2

CH2

C

COO-

COO-

O + NH4+

+ NADH+ H+

22-20

Fate of Carbon Skeleton

Insert Fig 22.8 4th and caption

22-21

22.8 the Urea CycleOxidative deamination produces large

amounts of ammonium ion which is toxic.

The pathway to eliminate ammonium ion is the Urea Cycle.

Urea is excreted in the urine.

Failure of enzymes in the urea cycle leads to hyperammonemia. In severe cases this leads to early death from toxic ammonium ion buildup. It can also lead to retardation, convulsions, and vomiting.

22-22

NH2

C OOPO3

2-

CO2 + NH4+ H2O

2 ATP2(ADP + Pi)

carbamoyl phosphate

NH2 CH2 CHNH3

+

COO-

3

NH2 CO

NH CH2 CHNH3

+

COO-

3

ornithine

citruline

In themitochondria

To cytosol

Urea Cycle-1

22-23

NH2 CO

NH CH2 CHNH3

+

COO-

3

-OOC CH

N

CH2COO-

NH2 C NH CH2 CHNH3

+

COO-

3

arginosuccinate

aspartate

Urea Cycle-2

incytosol

-OOC CH

NH3

+CH2COO

-

ATP

AMP + PPi

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-OOC CH

N

CH2COO-

NH2 C NH CH2 CHNH3

+

COO-

3

-OOC C

HCH

COO-

NH2

+

NH2 C NH CH2 CHNH3

+

COO-

3

fumarate

arginine

NH2

NH2 C O

H2O

ornithine

urea!

Urea Cycle-3

In cytosol

22-25

Starthere

NH2C OOPO3

2-

CO2 + NH4

+

Urea Cycle

H2O

2 ATP 2(ADP+Pi)

carbamoylphosphate

NH2 CO

NH CH2 CHNH3

+

COO-

3

ornithine

citrulline

arginosuccinate-OOC CH

NH3

+CH2COO

-

aspartate

ATP

AMP + PPi

-OOC CH

NCH2COO

-

NH2 C NH CH2 CHNH3

+

COO-

3

-OOC CH CH COO

-fumarate

NH2

+

NH2 C NH CH2 CHNH3

+

COO-

3arginine

NH2 CO

NH2ureaNH2 CH2 CH

NH3

+

COO-

3+

H2O

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22.9 Overview of Anabolism

Insert Fig 22.13

22-27

The End

Aerobic Respiration

And

Energy Production