Cellular Respiration

Chapter 3

Where did Bruce Lee get all that energy

from?

What is it?

• Cellular respiration– An aerobic process (requires oxygen)

– Uses chemical energy from glucose to make ATP

– Chemical energy is now stored in ATP for use throughout the body

O2

ATP36

glucose1Cellular resp.

Four Main Stages

1. Glycolysis• Anaerobic• In cytosol• breaks glucose (6C) into 2 pyruvate molecules

(3C)• releases ATP

2. Transition reaction (oxidative decarboxylation)

• Pyruvate converted to acetyl CoA releasing CO2

3. Kreb’s Cycle• Within mitochondrial matrix• Oxidize each acetyl CoA to CO2

• Releases ATP and co-enzymes (NADH, FADH2)

4. Electron Transport Chain• Along the inner mitochondrial membrane• Uses high energy electrons from NADH and

FADH2 to create an electrochemical proton (H+) gradient which powers ATP synthesis

Fermentation

• When oxygen is NOT available, cells can metabolize pyruvate (derived from glucose) by the process of fermentation.

Two Types

(i) alcohol fermentation: pyruvate (3C) converted (reduced) to ethyl alcohol (2C) and CO2; occurs in yeast cells

(ii) lactic acid fermentation: pyruvate(3C) converted (reduced) to lactic acid (3C) in muscle cells

Cellular Respiration

glucose + O2 CO2 + H2O + energy CO2 H2O

H+H+ EnergyO2

glucose

General Formula

This process begins with glucose. Once it enters a cell, the process of glycolysis begins immediately in the cytoplasm where enzymes are waiting.

Glycolysis (I) Overview

• This is the investment period of glycolysis• ATP is USED in order to “activate” glucose• This is accomplish by an enzyme mediated

process called: substrate level phosphorylation» Involving the transfer of a phosphate group

Numbering the Carbons of Glucose

glucose

C

C

C C

C

O

C

• In order to keep track of how glucose is modified and rearranged during glycolysis we number each carbon

1

23

4

5

6

P P P

glucose

C

C

C C

C

O

C

C

C

C C

C

O

C

P P

P

C

C

C

C

OCP C

C

C

C

C

OCP C P

C C CP CCC P

P P PP P

C

C

C C

C

O

CP

glucose

glucose-6-phosphate

fructose-6-phosphate

fructose-1-6-bisphosphate

2 molecules of

PGAL (glyceraldehyde-3-phosphate)

Glycolysis (I)

Glycolysis (I)

glucose

C

C

C C

C

O

C

C

C

C C

C

O

CP

C

C

C

C

OCP C

C

C

C

C

OCP C P

C C CP CCC P

glucose

glucose-6-phosphate

fructose-6-phosphate

fructose-1-6-biphosphate

2 molecules of

PGAL (glyceraldehyde-3-phosphate)

activation

isomerization

activation

cleavage

ADP

ATP

ADP

ATP

Glycolysis (I)

1. Activation: Phosphate from ATP is added to glucose to form glucose-6-phosphate. [substrate-level phosphorylation]

2. Isomerization: Glucose-6-phosphate is rearranged to form fructose-6-phosphate.

3. Activation: A second phosphate from another ATP is added to form fructose-1,6-bisphosphate. [substrate-level phosphorylation]

4. Cleavage: The unstable fructose-1,6-bisphosphate splits into phosphoglyceraldehyde (PGAL) and dihydroxyacetone phosphate (DHAP).

Investme

nt

Glycolysis (II) Overview

• This is the pay-off period of glycolysis• ATP and NADH (a high energy molecule) are

PRODUCED during glycolysis II• By the end of glycolysis II, glucose has been

broken down from 6 carbons to a 3 carbon compound called Pyruvate (pyruvic acid)

Glycolysis (II)

C C CP CCC P

C C CP CCC P

P PC C CP C C C P

NADNADH

NADNADH

Pi Pi

P P PP P

P PC C CP C C C P

PPP PP

C C C

P

CCC

P

P P PP P PPP PP

P P

C C C CCC

PGAL

PGAP

PGA

PEP

Pyruvate

H2

O

HH

H2

O

HH

Glycolysis (II)

C C CP CCC P

C C CP CCC P

P PC C CP C C C P

NADH NADH

P PC C CP C C C P

C C C

P

CCC

P

P P

C C C CCC

PGAL

PGAP

PGA

PEP

Pyruvate

ATP

ATP

ATP

ATP

activation / redox

dephosphorylation

isomerization / dehydration

dephosphorylation

H2

O

HH

H2

O

HH

5. Activation/Redox: Each molecule of PGAL is oxidized by NAD and gains a phosphate to form 1,3-bisphosphoglycerate (PGAP).

6. Phosphorylation: Each PGAP loses a phosphate to ADP resulting in 2 ATP and two 3-phosphoglycerate molecules (3-PGA).[substrate-level phosphorylation]

7. Isomerization: Both 3-PGA molecules are rearranged to form 2-phosphoglycerate (2-PGA).

[note: the text does not distinguish between 3-PGA and 2-PGA, but refers to both as PGA ]

8. Dehydration: Both 2-PGA molecules are oxidized to phosphoenol pyruvate (PEP) by the removal of water.

9. Phosphorylation: Each PEP molecule loses a phosphate to ADP resulting in 2 more ATP and 2 molecules of pyruvate. [substrate-level phosphorylation]

Glycolysis (II)

Pay-off

The Result

Energy in Glycolysis• Used 2 ATP• Made 4 ATP

Net Gain:

4ATP – 2ATP =

And

ATP2NADH2

(high energy molecule)

1 3

5

6

9

Notice: There is no oxygen used in glycolysis.

It is an anaerobic process

Glycolysis: overall reaction

C6H12O6 + 2ADP + 2P + 2NAD+ 2C3H4O3 + 2NADH + 2ATP

glucose (6C) pyruvate (3C)

O2

The Power House!

• In the cytosol, for each glucose molecule consumed, only 2 ATP were produced

• This means that 34 more ATP are made in the mitochondria!

• How do we get in there and what happens inside!?

nucleus

mitochondria

cytosolATP ATP

ATPATP

ATP

ATPATP

ATPATPATP

ATP

ATP

ATP ATP

ATPATP

ATP

ATP

ATP

ATP

ATPATP

ATPATP

ATP

ATP

ATP

ATP

ATP

ATPATP

ATP

ATPATP

ATP

ATP

Inside the Mitochondria

Inside the Mitochondria

• outer membrane: contains transport protein porin, which affects permeability

• inner membrane: contains the phospholipid cardiolipin that makes membrane impermeable to ions, a condition which is required for ATP production

• intermembrane space: fluid-filled area containing enzymes and hydrogen ions

• matrix: location of Kreb’s Cycle

• cristae: folds of the inner membrane where ETC enzymes are found

Transition Reaction

Intermembrane space mitochondrion

C – C – Cpyruvate multi-enzyme

pyruvate dehydrogenase complex

Transition Reaction

mitochondrion

C – C – Cpyruvate

1. Decarboxylation

C – C

CO2

Intermembrane space

Transition Reaction

mitochondrion

2. OxidationC – C

NAD+

C – C

NADH

Intermembrane space

Transition Reaction

mitochondrion

3. Attachment

C – C

CoA

Intermembrane space

Transition Reaction

mitochondrion

3. Attachment

C – C CoA

Acetyl CoA

Intermembrane space

Transition Reaction

A. Decarboxylation (-CO2) of pyruvate leaving a 2C molecule

B. Oxidation by NAD+ forming an acetate molecule.

C. Attachment of coenzyme A forming acetyl coA.

Steps A and B together are referred to as oxidative decarboxylation

Transition Reaction

In the transition reaction, for each molecule of pyruvate:

CO2

1 is released

and

NADH1 is produced

Transition Reaction

Remember: There are 2 pyruvates produced for each glucose. Therefore, for each glucose:

CO2

1 is released

and

NADH1 is produced

CO2

2 are released

and

NADH2 are prodcuedX2

Krebs Cycle

1. Acetyl coA breaks into coenzyme A, which is recycled, and an acetyl group (2C) which joins to oxaloacetate (4C) forming citrate (6C).

2. Citrate (6C) converts to isocitrate (6C).

3. Isocitrate (6C) loses CO2 and is then oxidized by NAD forming alpha-ketoglutarate (5C). [oxidative decarboxylation]

4. Alpha-ketoglutarate (5C) is converted to succinyl-coA (4C) in 3 steps:

(i) loss of CO2

(ii) oxidation by NAD+(iii) attachment of coenzyme A

Krebs Cycle

5. Succinyl coA (4C) is converted to succinate (4C) in the following way:

- coenzyme A breaks off and is recycled; phosphate attaches temporarily to succinate and is then transferred to GDP forming GTP; GTP transfers phosphate to ADP forming ATP (substrate level phosphorylation).

6. Succinate (4C) is oxidized by FAD to form fumarate (4C).

7. Water is added to fumarate (4C) to form malate (4C).

8. Malate (4C) is oxidized by NAD+ to form oxaloacetate, which is regenerated to begin the cycle again.

Krebs Cycle

Transition reaction

Krebs Cycle

Krebs Cycle

In the Krebs Cycle for each molecule of pyruvate:

CO2

2 are released

NADH3and

FADH21ATP1

are produced

Krebs CycleRemember: There are 2 pyruvates produced for each glucose. Therefore, for each glucose:

CO2

2 are released

NADH3and

FADH21ATP1

are prodcued

CO2

4 are released

NADH6and

FADH22ATP2

are produced

X2

The Story So Far

glucose1C – C

– Cpyruvate2 CO2

6

Tracking carbon:

(6C) (3C) (1C)

The Story So FarTracking High Energy Molecules

Metabolic Process ATP Produced High Energy Molecules

Glycolysis

Transition Reaction (x2)(oxidative decarboxylation)

Krebs Cycle (x2)

Total

NADH2ATP2 NADH6 FADH22

ATP2 NADH2 in cytosol

ATP4 NADH10

FADH22

Using the High Energy Molecules

• NADH and FADH2 have gained high energy electrons

• These electrons are donated to electron carrier proteins in the Electron Transport Chain (ETC).

• The energy from these electrons is then used to pump protons (H+) into the intermembrane space of the mitchondria

ATP Synthase

Electron Transport Chain

Electron Carriers:• 1. NADH reductase [protein]• 2. Coenzyme Q [non-protein]• 3. Cytochrome b1 c1

• 4. Cytochrome c• 5. Cytochrome c oxidase

Cristae QC

NADHreductase

Co-enzymeQ

Cytochromeb1c1

Cytochromec

Cytochrome coxidase

[protein]

not part of the ETC

Electron Transport Chain

• To pass electrons along ETC, each carrier is reduced (gains electrons) then oxidized (donates electrons)

• Curious? Where do these electrons come from?Electrons come from hydrogen atoms (H atoms separate into electrons and protons)

Cristae QC

Electron Transport Chain

1) NADH donates a pair of electrons to NADH reductase

2) electrons continue along ETC via sequential oxidations and reductions

Cristae QC

NADH

NAD+

Electron Transport Chain

1) FADH2 donates a pair of electrons to coenzyme Q

2) electrons also continue along ETC

CristaeC

Q

FADH2

Electron Transport Chain

CristaeC

Q

1) FADH2 donates a pair of electrons to coenzyme Q

2) electrons also continue along ETC

For each NADH, 6 H+ are pumped across the mitochondrion inner membrane

Cristae QC

NADH

NAD+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

CristaeC

Q

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+ H+

H+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

For each NADH, 6 H+ are pumped across the mitochondrion inner membrane

Oxygen is the final electron acceptor and is converted to H2O

O2

H2

O

H+H+

CristaeC

Q

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+ H+

H+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

For each FADH2, 4 H+ are pumped across the mitochondrion inner membrane

O2

H2

O

H+H+

FADH2

CristaeC

Q

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

The electrochemical proton gradient(sometimes referred to as the proton motive force)

H+

H+

H+H+

High Proton Concentration

Low Proton Concentration

Gra

die

nt

CristaeC

Q

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

• Using the energy stored in the proton gradient, ATP is generated using oxidative phosphorylation: formation of ATP coupled to oxygen consumption

H+

H+

H+H+

ATP

Using the electrochemial proton gradient to produce ATP from ADP is called chemiosmosis

CristaeC

Q

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

1 ATP is generated for each proton pair flowing through ATP synthase.

H+

H+

H+H+

ATP

NADHPumps

H+H+6

ATPATP

3

CristaeC

Q

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

1 ATP is generated for each proton pair flowing through ATP synthase.

H+

H+

H+H+

ATP

FADH2

PumpsH+

H+4

ATP

2

• ATP synthase works a bit like a water mill

The WHOLE process…

Cristae QC

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

The WHOLE process…

Cristae QC

NADH

NAD+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

CristaeC

Q

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+ H+

H+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

O2

H2

O

H+H+

The WHOLE process…

CristaeC

Q

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+H+

ATPATPATP

The WHOLE process…

CristaeC

Q

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+ H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+H+

ATPATPATP

The WHOLE process…

Summing up ATPRemember: BEFORE the ETC we had…

Metabolic Process ATP Produced High Energy Molecules

Glycolysis

Transition Reaction (x2)(oxidative decarboxylation)

Krebs Cycle (x2)

Total

NADH2ATP2 NADH6 FADH22

ATP2 NADH2 in cytosol

ATP4 NADH10

FADH22

Summing up ATPIn the Electron Transport Chain

Molecules from High Energy Molecules

ATP produced in ETC

Glycolysis

Transition Reaction (x2)(oxidative decarboxylation)

Krebs Cycle (x2)

Total

NADH2NADH6 FADH22

NADH2 in cytosol

NADH10

FADH22

ATP4ATP6

ATP22 ATP32

Summing up ATPIN TOTAL

Molecules from High Energy Molecules

ATP produced in ETC

Glycolysis

Transition Reaction (x2)(oxidative decarboxylation)

Krebs Cycle (x2)

Total

NADH2NADH6 FADH22

NADH2 in cytosol

NADH10

FADH22

ATP4ATP6

ATP22 ATP32

ATP34

ATP2+ From Glycolysis

ATP2

Summing up ATPIN TOTAL

Molecules from High Energy Molecules

ATP produced in ETC

Glycolysis

Transition Reaction (x2)(oxidative decarboxylation)

Krebs Cycle (x2)

Total

NADH2NADH6 FADH22

NADH2 in cytosol

NADH10

FADH22

ATP4ATP6

ATP22 ATP34

ATP36

ATP2

ATP2

+ From Krebs Cycle ATP2

glucose + oxygen carbon dioxide + water + energy

Overall Reaction

glucose1 CO2

6NAD+1

0 FAD2

NADH10 FADH22

NAD+10 FAD2

O2 H2OH+H+

Catalysts

ATP36

glucose

O2

CO2

Energy

H2OH+H+

glucose + oxygen carbon dioxide + water + energy

Overall Reaction

glucose1 CO2

6NAD+1

0 FAD2

O2 H2OH+H+

ATP36

Phase (location)

Glycolysis (cytosol)

Transition Reaction (mito.)

Kreb’s Cycle (mito.)

ETC (mito.)

some

some