Cellular Respiration

A.P. Biology

Energy

– Flows into an ecosystem as sunlight and leaves as heat

Light energy

ECOSYSTEM

CO2 + H2O

Photosynthesisin chloroplasts

Cellular respiration

in mitochondria

Organicmolecules

+ O2

ATP

powers most cellular work

Heatenergy

Figure 9.2

Catabolic pathways yield energy by oxidizing organic

fuels• The breakdown of organic molecules is

exergonic

• Fermentation– Is a partial degradation of sugars that occurs

without oxygen

Catabolic pathways yield energy by oxidizing organic

fuels

• Cellular respiration– Is the most prevalent and efficient

catabolic pathway– Consumes oxygen and organic

molecules such as glucose– Yields ATP

Redox Reactions: Oxidation and Reduction

• Catabolic pathways yield energy– Due to the transfer of electrons

• Redox reactions– Transfer electrons from one reactant to another by

oxidation and reduction

• Oxidation– A substance loses electrons, or is oxidized

• Reduction– A substance gains electrons, or is reduced

becomes oxidized(loses electron) becomes reduced

(gains electron)

Some redox reactions

– Do not completely exchange electrons– Change the degree of electron sharing in

covalent bonds

CH4

H

H

HH

C O O O O OC

H H

Methane(reducingagent)

Oxygen(oxidizingagent)

Carbon dioxide Water

+ 2O2 CO2 + Energy + 2 H2O

becomes oxidized

becomes reduced

Reactants Products

Figure 9.3

Oxidation of Organic Fuel Molecules During Cellular

Respiration

• During cellular respiration– Glucose is oxidized and oxygen is

reduced

C6H12O6 + 6O2 6CO2 + 6H2O + Energy

becomes oxidized

becomes reduced

G = -686 kcal/mol

Step by step catabolism of glucose

• If electron transfer is not stepwise– A large release

of energy occurs– As in the

reaction of hydrogen and oxygen to form water

(a) Uncontrolled reaction

Fre

e en

ergy

, G

H2O

Explosiverelease of

heat and lightenergy

Figure 9.5 A

H2 + 1/2 O2

ETC

• The electron transport chain– Passes electrons in

a series of steps – Uses the energy

from the electron transfer to form ATP

2 H 1/2 O2

(from food via NADH)

2 H+ + 2 e–

2 H+

2 e–

H2O

1/2 O2

Controlled release of energy for synthesis of

ATP ATP

ATP

ATP

Electro

n tran

spo

rt chain

Fre

e en

ergy

, G

(b) Cellular respiration

+

Figure 9.5 B

NAD – Nicotinamide Adenine Dinucleotide

(Electron Acceptor)• Electrons from organic compounds

– Are usually 1st transferred to NAD+, a coenzyme

NAD+

HO

O

O O–

O

O O–

O

O

O

P

P

CH2

CH2

HO OHH

HHO OH

HO

H

H

N+

C NH2

HN

H

NH2

N

N

Nicotinamide(oxidized form)

NH2+ 2[H]

(from food)

Dehydrogenase

Reduction of NAD+

Oxidation of NADH

2 e– + 2 H+

2 e– + H+

NADH

OH H

N

C +

Nicotinamide(reduced form)

N

Figure 9.4

Dehydragenase – removes 2 hydrogen atoms

NADH

• NADH, the reduced form of NAD+

– Passes the electrons to the electron transport chain

– Electrons are ultimately passed to a molecule of oxygen (Final electron acceptor)

G = -53 kcal/mol

Food NADH ETC Oxygen

Electron path in respiration

Cellular Respiration

• Respiration is a cumulative function of three metabolic stages– Glycolysis– The citric acid cycle (TCA or Krebbs)– Oxidative phosphorylation

C6H12O6 + 6O2   <---->   6 CO2 + 6 H20    + e- --->    36-38 ATP                                 G  =  -686 Kc/mole                                263Kc  = 38%

Respiration

• Glycolysis– Breaks down glucose into two molecules of

pyruvate

• The citric acid cycle– Completes the breakdown of glucose

• Oxidative phosphorylation– Is driven by the electron transport chain– Generates ATP

Respiration Overview

Figure 9.6

Electronscarried

via NADH

GlycolsisGlucos

ePyruvate

ATP

Substrate-levelphosphorylation

Electrons carried via NADH and

FADH2

Citric acid cycle

Oxidativephosphorylation:

electron transport and

chemiosmosis

ATPATP

Substrate-levelphosphorylation

Oxidativephosphorylation

MitochondrionCytosol

2 ATP 2 ATP 34 ATP

Substrate Level Phosphorylation

• Both glycolysis and the citric acid cycle– Can generate ATP by substrate-level

phosphorylation

Figure 9.7

Enzyme Enzyme

ATP

ADP

Product

SubstrateP

+

Glycolysis• Harvests energy by oxidizing

glucose to pyruvate

• Glycolysis– Means “splitting of sugar”– Breaks down glucose into

pyruvate– Occurs in the cytoplasm of the cell

• Two major phases– Energy investment phase– Energy payoff phase

Glycolysis Citricacidcycle

Oxidativephosphorylation

ATP ATP ATP

2 ATP

4 ATP

used

formed

Glucose

2 ATP + 2

P

4 ADP + 4 P

2 NAD+ + 4 e- + 4 H +

2 NADH

+ 2 H+

2 Pyruvate + 2 H2O

Energy investment phase

Energy payoff phase

Glucose 2 Pyruvate + 2 H2O4 ATP formed – 2 ATP

used 2 ATP

2 NAD+ + 4 e– + 4 H +

2 NADH

+ 2 H+

Figure 9.8

Energy Investment Phase

Energy Payoff Phase

Glycolysis Summary

The First Stage of Glycolysis •Glucose (6C) is broken down into 2 PGAL's (3C Phosphoglyceraldehyde) •This requires two ATP's

The Second Stage of Glycolysis •2 PGAL's (3C) are converted to 2 pyruvates •This creates 4 ATP's and 2 NADH's •The net ATP production of Glycolysis is 2 ATP's

Citric Acid Cyclea.k.a. Krebs Cycle

• Completes the energy-yielding oxidation of organic molecules

• The citric acid cycle– Takes place in the matrix of the

mitochondrion

Krebs's Cycle (citric acid cycle, TCA cycle)

•Goal: take pyruvate and put it into the Krebs's cycle, producing NADH and FADH2

•Where: the mitochondria

•There are two steps •The Conversion of Pyruvate to Acetyl CoA •The Kreb's Cycle proper

•In the Krebs's cycle, all of Carbons, Hydrogens, and Oxygeng in pyruvate end up as CO2 and H2O

•The Krebs's cycle produces 2 ATP's, 8 NADH's, and 2FADH2's per glucose molecule

Fate of Pyruvate

Carboxyl (coo-) is cleaved CO2 is released

–Pyruvate must first be converted to acetyl CoA, which links the cycle to glycolysis

Before the citric acid cycle can begin

CYTOSOL MITOCHONDRION

NADH + H+NAD+

2

31

CO2 Coenzyme APyruvate

Acetyle CoA

S CoA

C

CH3

O

Transport protein

O–

O

O

C

C

CH3

Figure 9.10

ATP

2 CO2

3 NAD+

3 NADH

+ 3 H+

ADP + P i

FAD

FADH2

Citricacidcycle

CoA

CoA

Acetyle CoA

NADH+ 3 H+

CoA

CO2

Pyruvate(from glycolysis,2 molecules per glucose)

ATP ATP ATP

Glycolysis Citricacidcycle

Oxidativephosphorylation

Figure 9.11

An overview of the citric acid cycle

Acetyl CoA

NADH

Oxaloacetate

CitrateMalate

Fumarate

SuccinateSuccinyl

CoA

-Ketoglutarate

Isocitrate

Citricacidcycle

S CoA

CoA SH

NADH

NADH

FADH2

FAD

GTP GDP

NAD+

ADP

P i

NAD+

CO2

CO2

CoA SH

CoA SH

CoAS

H2O

+ H+

+ H+ H2O

C

CH3

O

O C COO–

CH2

COO–

COO–

CH2

HO C COO–

CH2

COO–

COO–

COO–

CH2

HC COO–

HO CHCOO–

CH

CH2

COO–

HO

COO–

CH

HC

COO–

COO–

CH2

CH2

COO–

COO–

CH2

CH2

C O

COO–

CH2

CH2

C O

COO–

1

2

3

4

5

6

7

8

Glycolysis Oxidativephosphorylation

NAD+

+ H+

ATP

Citricacidcycle

Figure 9.12

The Kreb's Cycle•6 NADH's are generated •2 FADH2 is generated •2 ATP are generated •4 CO2's are released

Net Engergy Production from Aerobic Respiration

•Glycolysis: 2 ATP •Kreb's Cycle: 2 ATP •Electron Transport Phosphorylation: 32 ATP

•Each NADH produced in Glycolysis is worth 2 ATP (2 x 2 = 4) - the NADH is worth 3 ATP, but it costs an ATP to transport the NADH into the mitochondria, so there is a net gain of 2 ATP for each NADH produced in gylcolysis •Each NADH produced in the conversion of pyruvate to acetyl COA and Kreb's Cycle is worth 3 ATP (8 x 3 = 24) •Each FADH2 is worth 2 ATP (2 x 2 = 4) •4 + 24 + 4 = 32

•Net Energy Production: 36 ATP

Energy Yields:

•Glucose: 686 kcal/mol

•ATP: 7.5 kcal/mol

•7.5 x 36 = 270 kcal/mol for all ATP's produced

•270 / 686 = 39% energy recovered from aerobic respiration

•During oxidative phosphorylation, chemiosmosis couples electron transport to ATP synthesis

•NADH and FADH2

–Donate electrons to the electron transport chain, which powers ATP synthesis via oxidative phosphorylation

After the Krebs Cycle…

The Pathway of Electron Transport

•In the electron transport chain

–Electrons from NADH and FADH2 lose energy in several steps

•At the end of the chain

–Electrons are passed to oxygen, forming water

H2O

O2

NADH

FADH2

FMN

Fe•S Fe•S

Fe•S

O

FAD

Cyt b

Cyt c1

Cyt c

Cyt a

Cyt a3

2 H + + 12

I

II

III

IV

Multiproteincomplexes

0

10

20

30

40

50

Fre

e e

ner

gy

(G)

rela

tive

to O

2 (k

cl/m

ol)

Figure 9.13

Chemiosmosis: The Energy-Coupling Mechanism

•ATP synthase

–Is the enzyme that actually makes ATP

INTERMEMBRANE SPACE

H+

H+

H+

H+

H+

H+ H+

H+

P i

+ADP

ATP

A rotor within the membrane spins clockwise whenH+ flows past it down the H+

gradient.

A stator anchoredin the membraneholds the knobstationary.

A rod (for “stalk”)extending into the knob alsospins, activatingcatalytic sites inthe knob.

Three catalytic sites in the stationary knobjoin inorganic Phosphate to ADPto make ATP. MITOCHONDRIAL MATRIXFigure 9.14

–Electron transfer causes protein complexes to pump H+ from the mitochondrial matrix to the intermembrane space

•The resulting H+ gradient

–Stores energy

–Drives chemiosmosis in ATP synthase

–Is referred to as a proton-motive force

ETC

Chemiosmosis

–Is an energy-coupling mechanism that uses energy in the form of a H+ gradient across a membrane to drive cellular work

H+ gradient = Proton motive force

Oxidativephosphorylation.electron transportand chemiosmosis

Glycolysis

ATP ATP ATP

InnerMitochondrialmembrane

H+

H+H+

H+

H+

ATPP i

Protein complexof electron carners

Cyt c

I

II

III

IV

(Carrying electronsfrom, food)

NADH+

FADH2

NAD+

FAD+ 2 H+ + 1/2 O2

H2O

ADP +

Electron transport chainElectron transport and pumping of protons (H+),

which create an H+ gradient across the membrane

ChemiosmosisATP synthesis powered by the flowOf H+ back across the membrane

ATPsynthase

Q

Oxidative phosphorylation

Intermembranespace

Innermitochondrialmembrane

Mitochondrialmatrix

Figure 9.15

•During respiration, most energy flows in this sequence

–Glucose to NADH to electron transport chain to proton-motive force to ATP

An Accounting of ATP Production by Cellular Respiration

Electron shuttlesspan membrane

CYTOSOL 2 NADH

2 FADH2

2 NADH 6 NADH 2 FADH22 NADH

Glycolysis

Glucose2

Pyruvate

2AcetylCoA

Citricacidcycle

Oxidativephosphorylation:electron transport

andchemiosmosis

MITOCHONDRION

by substrate-levelphosphorylation

by substrate-levelphosphorylation

by oxidative phosphorylation, dependingon which shuttle transports electronsfrom NADH in cytosol

Maximum per glucose:About

36 or 38 ATP

+ 2 ATP + 2 ATP + about 32 or 34 ATP

or

Figure 9.16

•Fermentation enables some cells to produce ATP without the use of oxygen

•Glycolysis

–Can produce ATP with or without oxygen, in aerobic or anaerobic conditions

–Couples with fermentation to produce ATP

Anaerobic Respiration

•Fermentation consists of

–Glycolysis plus reactions that regenerate NAD+, which can be reused by glyocolysis

•Alcohol fermentation

–Pyruvate is converted to ethanol in two steps, one of which releases CO2

•Lactic acid fermentation

–Pyruvate is reduced directly to NADH to form lactate as a waste product

Anaerobic Respiration

2 ADP + 2 P1 2 ATP

GlycolysisGlucose

2 NAD+ 2 NADH

2 Pyruvate

2 Acetaldehyde 2 Ethanol

(a) Alcohol fermentation

2 ADP + 2 P1 2 ATP

GlycolysisGlucose

2 NAD+ 2 NADH

2 Lactate

(b) Lactic acid fermentation

H

H OH

CH3

C

O –

OC

C O

CH3

H

C O

CH3

O–

C O

C O

CH3O

C O

C OHH

CH3

CO22

Figure 9.17

Glucose

CYTOSOL

Pyruvate

No O2 presentFermentation

O2 present Cellular respiration

Ethanolor

lactate

Acetyl CoA

MITOCHONDRION

Citricacidcycle

Figure 9.18

Pyruvate is a key juncture in catabolism

•Glycolysis

–Occurs in nearly all organisms

–Probably evolved in ancient prokaryotes before there was oxygen in the atmosphere

Amino acids

Sugars Glycerol Fattyacids

Glycolysis

Glucose

Glyceraldehyde-3- P

Pyruvate

Acetyl CoA

NH3

Citricacidcycle

Oxidativephosphorylation

FatsProteins Carbohydrates

Figure 9.19

•Cellular respiration

–Is controlled by allosteric enzymes at key points in glycolysis and the citric acid cycle

Glucose

Glycolysis

Fructose-6-phosphate

Phosphofructokinase

Fructose-1,6-bisphosphateInhibits Inhibits

Pyruvate

ATPAcetyl CoA

Citricacidcycle

Citrate

Oxidativephosphorylation

Stimulates

AMP

+

– –

Figure 9.20