2006-2007

Cellular RespirationHarvesting Chemical Energy

ATP

Harvesting stored energy Glucose is the model

catabolism of glucose to produce ATP

C6H12O6 6O2 ATP 6H2O 6CO2+ + +

CO2 + H2O + heatfuel

(carbohydrates)

COMBUSTION = making a lot of heat energy by burning fuels in one step

RESPIRATION = making ATP (& some heat)by burning fuels in many small steps

CO2 + H2O + ATP (+ heat)

ATPglucose

glucose + oxygen energy + water + carbondioxide

res

pir

ati

on

O2 O2

+ heat

enzymesATP

How do we harvest energy from fuels? Digest large molecules into smaller ones

break bonds & move electrons from one molecule to another as electrons move they “carry energy” with them that energy is stored in another bond,

released as heat or harvested to make ATP

e-

+ +e-

+ –loses e- gains e- oxidized reduced

oxidation reduction

redox

e-

How do we move electrons in biology? Moving electrons in living systems

electrons cannot move alone in cells electrons move as part of H atom move H = move electrons

pe

+

H

+H

+ –loses e- gains e- oxidized reduced

oxidation reduction

C6H12O6 6O2 6CO2 6H2O ATP+ + +

oxidation

reductionHe-

Coupling oxidation & reduction REDOX reactions in respiration

strip off electrons from C-H bonds by removing H atoms C6H12O6 CO2 = the fuel has been oxidized

electrons attracted to more electronegative atoms

in biology, the most electronegative atom? O2 H2O = oxygen has been reduced

couple REDOX reactions & use the released energy to synthesize ATP

C6H12O6 6O2 6CO2 6H2O ATP+ + +

oxidation

reduction

O

Energy Transfer Substrate level phosphorylation Oxidative phosphorylation

Substrate Level Phosphyralation ATP is formed directly in an enzyme-

catalyzed reaction Phosphate containing group transfers a

phosphate directly to ADP 30.5 kJ/mol of potential energy is also

transferred

Substrate Level Phosphorylation

1) Occurs in glycolysis & Krebs cycle

2) Energy and phosphate are transferred to ADP using an enzyme, to form ATP.

3) PEP (phosphoenolpyruvate) is oxidized.

4) Whereas ADP is reduced. 5) ATP has gained Free Energy

from PEP. ATP can now do work.

Oxidative Phosphorylation ATP is formed indirectly Involves a number of sequential redox

reactions Oxygen is the final electron acceptor More complex More ATP generated

Moving electrons in respiration Electron carriers move electrons by

shuttling H atoms around NAD+ NADH (reduced) FAD+2 FADH2 (reduced)

+ Hreduction

oxidation

PO–

O–

O

–O

PO–

O–

O

–O

CC

O

NH2

N+

H

adenine

ribose sugar

phosphates

NAD+

nicotinamideVitamin B3niacin

PO–

O–

O

–O

PO–

O–

O

–O

CC

O

NH2

N+

HNADH

carries electrons as a reduced molecule

reducing power!

How efficient!Build once,

use many ways

H

like $$in the bank

Oxidative Phosphorylation, NAD+ Nicotinamide adenine dinucleotide,

NAD+ Coenzyme Vitamin B3 Improvements in energy functions

Increasing NAD+ increases availability of these molecules for metabolism

Found in various meats, peanuts and sunflower seeds

Oxidative Phosphorylation, FADFlavin adenine dinucleotide, FAD

Coenzyme Built from riboflavin

Vitamin B2 Found in meats (liver, kidney & heart),

almonds, mushrooms, soybean, green leafy vegetables

Also reduced by two hydrogen atoms Reduced form FADH2

In one reaction of the Krebs cycle

NADH and FADH2 Act as mobile energy carriers Energy harvesting reactions Eventually transfer most of their energy

to ATP molecules

Oxidative Phosphorylation Begins with nicotinamide adenine dinucleotide

(NAD+) Removes 2H atoms from portion of original glucose Electrons are passed from the NADH to

dehydrogenase NADH becomes oxidized

DehydrogenaseDehydrogenase

NADH2

ee ee

NAD+

Oxidative Phosphorylation Occurs in:

One reaction of glycolysis During pyruvate oxidation Three reactions of Krebs cycle

Energy Transfer Goal is to trap energy Substrate level phosphorylation

ATP is formed by enzyme catalyzed reaction 6 ATP made per glucose molecule

Oxidative phosphorylation Many redox reactions form ATP indirectly

More ATP (30) produced per glucose molecule

Forms reduced coenzymes NADH and FADH2 that will eventually transfer their free energy to ATP

Overview of cellular respiration 3 metabolic stages

Anaerobic respiration1. Glycolysis

respiration without O2

in cytosol

Aerobic respiration respiration using O2

in mitochondria

2. Krebs cycle

3. Electron transport chain

C6H12O6 6O2 ATP 6H2O 6CO2+ + + (+ heat)

Glycolysis and Cancer

2007-2008

Cellular RespirationStage 1:

Glycolysis

Glycolysis

glucose pyruvate2x6C 3C

In thecytosol?

Why doesthat make

evolutionarysense?

That’s not enoughATP for me!

Breaking down glucose “glyco – lysis” (splitting sugar)

ancient pathway which harvests energy where energy transfer first evolved transfer energy from organic molecules to ATP still is starting point for ALL cellular respiration

but it’s inefficient generate only 2 ATP for every 1 glucose

occurs in cytosol

Evolutionary perspective Prokaryotes

first cells had no organelles Anaerobic atmosphere

life on Earth first evolved without free oxygen (O2) in atmosphere

energy had to be captured from organic molecules in absence of O2

Prokaryotes that evolved glycolysis are ancestors of all modern life ALL cells still utilize glycolysis

You meanwe’re related?

Do I have to invitethem over for the holidays?

Enzymesof glycolysis are“well-conserved”

10 reactions convert

glucose (6C) to 2 pyruvate (3C)

produces: 4 ATP & 2 NADH

consumes:2 ATP

net yield: 2 ATP & 2 NADH

glucoseC-C-C-C-C-C

fructose-1,6bPP-C-C-C-C-C-C-P

DHAPP-C-C-C

G3PC-C-C-P

pyruvateC-C-C

Overview

DHAP = dihydroxyacetone phosphateG3P = glyceraldehyde-3-phosphate

ATP2

ADP2

ATP4

ADP4

NAD+2

2Pi

enzyme

enzyme

enzyme enzyme

enzyme

enzyme

enzyme

enzyme

2Pi

2H2

DEMO

Pi

3

6

4,5

ADP

NAD+

Glucose

hexokinase

phosphoglucoseisomerase

phosphofructokinase

Glyceraldehyde 3-phosphate (G3P)

Dihydroxyacetonephosphate

Glucose 6-phosphate

Fructose 6-phosphate

Fructose 1,6-bisphosphate

isomerase

glyceraldehyde3-phosphate

dehydrogenase

aldolase

1,3-Bisphosphoglycerate(BPG)

1,3-Bisphosphoglycerate

(BPG)

1

2

ATP

ADP

ATP

NADH

NAD+

NADH

Pi

CH2

C O

CH2OH

P O

CH2 O P

O

CHOH

C

CH2 O P

O

CHOH

CH2 O PO

CH2OP

O

PO

CH2

H

CH2OHO

CH2 POO

CH2OH

P O

1st half of glycolysis (5 reactions)

Glucose “priming”

get glucose ready to split

split destabilized glucose

2nd half of glycolysis (5 reactions)

Payola!Finally some

ATP!

7

8

H2O9

10

ADP

ATP

3-Phosphoglycerate(3PG)

3-Phosphoglycerate(3PG)

2-Phosphoglycerate(2PG)

2-Phosphoglycerate(2PG)

Phosphoenolpyruvate(PEP)

Phosphoenolpyruvate(PEP)

Pyruvate Pyruvate

phosphoglyceratekinase

phosphoglycero-mutase

enolase

pyruvate kinase

ADP

ATP

ADP

ATP

ADP

ATP

H2O

CH2OH

CH3

CH2

O-

O

C

PH

CHOH

O-

O-

O-

C

C

C

C

C

C

P

P

O

O

O

O

O

O

CH2

NAD+

NADH

NAD+

NADH

Energy Harvest G3P

C-C-C-PPiPi 6

DHAPP-C-C-C

NADH production

ATP production G3P pyruvate

Regulation of Glycolysis and Cancer

Glycolysis summary

net yield

4 ATP

ENERGY INVESTMENT

ENERGY PAYOFF

G3PC-C-C-P

NET YIELD

like $$in the bank

-2 ATP

Substrate-level Phosphorylation

I get it!The Pi camedirectly from

the substrate!

H2O9

10

Phosphoenolpyruvate(PEP)

Phosphoenolpyruvate(PEP)

Pyruvate Pyruvate

enolase

pyruvate kinaseADP

ATP

ADP

ATP

H2O

CH3

O-

O

C

O-

C

C

C

P

O

O

O

CH2

In the last steps of glycolysis, where did the P come from to make ATP?

ATP

Energy accounting of glycolysis

Net gain = some energy investment (-2 ATP) small energy return (4 ATP + 2 NADH)

1 6C sugar

glucose pyruvate2x6C 3C

All that work! And that’s all

I get?

Butglucose has

so much moreto give!

2006-2007

Cellular RespirationStage 2:

Citric Acid Cycle orKrebs Cycle

pyruvate CO2

Glycolysis is only the start Glycolysis

Pyruvate has more energy to yield

2x6C 3Cglucose pyruvate

3C 1C

Cellular respiration

pyruvate acetyl CoA + CO2

Oxidation of pyruvate

NAD

3C 2C 1C[2x ] releases reduces produces

Citric Acid cycle1937 | 1953

Hans Krebs1900-1981

citrate

acetyl CoACount the carbons!

pyruvate

x2

oxidationof sugars

This happens twice for each glucose molecule

6C

5C

citrate

acetyl CoACount the electron carriers!

pyruvate

reductionof electron

carriers

This happens twice for each glucose molecule x2

CO2

NADH

What’s the point?

Electron Carriers = Hydrogen Carriers

What’s so important about

electron carriers?

H+

H+H+

H+

H+ H+

H+H+H+

ATP

ADP+ Pi

Energy accounting of Citric Acid cycle

Net gain =

1 ADP 1 ATPATP

2x

4 NAD + 1 FAD 4 NADH + 1 FADH2

pyruvate CO2

3C 3x 1C

Value of Citric Acid cycle? If the yield is only 2 ATP then how was the

Citric Acid cycle an adaptation?

like $$in the bank

The Second Law of Thermodynamics states that spontaneous processes tend to increase the entropy (disorder) of the universe.  Why would this law favor a glucose molecule being broken down?

The First Law of Thermodynamics states that energy is neither created or destroyed in any process, including chemical reactions.  Looking at the big picture of life, and assuming energy used by organisms comes from the sun, how does ATP production by cellular respiration obey the First Law?