Aerobic Cellular Respiration

• Process that extracts energy from food (mainly glucose, but also proteins and lipids) in the presence of oxygen –obligate aerobes

• The energy that is extracted is used to synthesize ATP• ATP is used to supply energy directly to cells to drive

chemical reactions

Why Make ATP?

• Referred to as energy currency of the cell• Provide energy for chemical reactions to take place

in our body (cells)

Mitochondria• Site of cellular respiration (where ATP is made)• Conists of – Outer membrane– Inner membrane– Matrix– Cristae

Aerobic Cellular Respiration• Divided into 4 stages

1. Glycolysis2. Pyruvate oxidation3. Citric acid cycle4. Electron transport chain and

oxidative phosphorylation• Each Stage involves the

transfer of FREE ENERGY• ATP is produced in two

different ways– Substrate-level phosphorylation– Oxidative phosphorylation

Aerobic Respiration• Location of each

Stage• Glycolysis– Cytosol

• Pyruvate Oxidation– Mitochondrial matrix

• Citric Acid Cycle– Mitochondrial matrix

• Electron Transport – Inner mitochondrial

membrane

Glycolysis• Primitive

– Process found in almost all organisms– Both prokaryotes and eukaryotes

• Does not require O₂• Involves

– Soluble enzymes (10 sequential enzyme-catalyzed

reactions) – Oxidation of a 6-carbon sugar glucose

• Produces– 2 molecules of pyruvate (3-

carbon molecule)– 4 ATP and 2 NADH

• Two Phases in which this occurs – Initial energy investment phase – Energy payoff phase

This process is for the conversion of only ONE glucose molecule!!!

Glycolysis Overview

Glycolysis Overview • Initial energy investment

phase– 2 ATP are consumed

• Energy payoff phase– 4 ATP produced– 2 NADH molecules are

synthesized

Overall NET reaction; Glucose + 2 ADP + 2 Pi + 2 NAD⁺ → 2

pyruvate + 2 ATP + 2 NADH + 2H⁺• 62 kJ of energy is stored by the

synthesis of 2 ATP molecules • Rest of the free energy is stored in

the 2 pyruvate molecules

Substrate-Level Phosphorylation• Phosphate groups

are attached to ADP from a substrate forming ATP (enzyme catalyzed reaction)

• ALL ATP molecules are produced this way in Glycolysis

Pyruvate• Pyruvate can take 2 paths

from this point:1. Aerobic Respiration

(with oxygen) – Pyruvate moves into

mitochondria and ATP is made via Krebs Cycle and Electron Transport Chain

2. Anaerobic Respiration (without oxygen)– Pyruvate stays in

cytoplasm and is converted into lactic acid -Lactic Acid Fermentation

Pyruvate Oxididation • Remember glycolysis occurs in the cytosol of the cell • The Citric Acid Cycle (next step) occurs in the mitochondrial

matrix• Pyruvate must pass through the inner and outer membrane

of the mitochondrion

Pyruvate Oxidation• Outer membrane– Pyruvate diffuses across the outer membrane through large pores of

mitochondrion• Inner membrane– Pyruvate-specific membrane carrier is required

• Inside Matrix– Pyruvate is converted into an acetyl group– Acetyl group is bonded to coenzyme A– Produces an acetyl-CoA complex

Pyruvate OxidationConversion of pyruvate to acetyl-CoAInvolves 2 Reactions• Catalyzed by pyruvate dehydrogenase • Decarboxylation reaction

– Carboxyl group (-COO⁻) of pyruvate is removed – Produces

• CO₂

• Dehydrogenation reaction– 2 electrons and a proton are transferred – Produces

• NADH • H⁺ in solution

Net reaction2 pyruvate + 2 NAD⁺ + 2 CoA → 2 acetyl-CoA + 2 NADH + 2 H⁺ + 2 CO₂

Pyruvate Oxidation• Acetyl

group reacts with the sulfur atom of coenzyme A

• Acetyl-CoA is the molecule that will start the Citric Acid Cycle

Citric Acid Cycle• Discovered by– Sir Hans Krebs

(1900-1981)– Consists of 8

enzyme catalyzed reaction

– ALL ATP are produced by substrate-level phosphorylation

Citric Acid Cycle Overview • 2 molecules of

pyruvate are converted to Acetyl-CoA

• Citric Acid Cycle goes through two turns for every single glucose molecule that is oxidized

1 Turn• Acetyl-CoA + 3 NAD⁺ +

FAD + ADP + Pi → 2 CO₂ + 3 NADH + 3 H⁺ + FADH₂ + ATP + CoA

• ATP is synthesized by substrate level phosphorylation coupled by GTP

Citric Acid Cycle Overview

Citric Acid Cycle• ALL of the carbon atoms that make up a glucose

molecule are converted into CO₂– oxidation of pyruvate – acetyl groups

6CO₂

Oxidation of ONE Glucose Molecule

Total # of NET Molecules Produced

NADH FADH₂ CO₂ ATP

Glycolysis 2 0 0 2

Pyruvate Oxidation

2 0 2 0

Citric Acid Cycle

6 2 4 2

Electron Transport Chain (Chemiosmosis)• Process that extracts potential energy that is stored in NADH and

FADH₂– These molecules were formed during glycolysis, pyruvate oxidation, and

citric acid cycle– Redox reactions – transfer of electrons

• This energy is used to synthesize additional ATP (A lot more) via oxidative phosphorylation

The Electron Transport Chain• Occurs on the inner mitochondrial membrane• Facilitates the transfer of electrons from NADH and

FADH₂ to O₂

The Electron Transport Chain• Composed of • 4 Complexes

– Complex I, NADH dehydrogenase – Complex II, succinate

dehydrogenase– Complex III, cytochrome complex– Complex IV, cytochrome oxidase

• 2 Electron shuttles– Ubiquinone (UQ)

• Hydrophobic molecule – shuttles electrons from complex I and II to complex III

– Cytochrome C (cyt c)• Shuttles electrons from complex III

to complex IV

The Driving Force Behind Electron Transport • Complexes I, III, IV• Each has a cofactor• Each cofactor has

increasing electronegativity

• Alternate between reduced and oxidized states

• Electrons move towards more electronegative molecules (downstream)

• Final electron acceptor – OXYGEN (most electronegative)

• Pulls electrons from complex IV

How a Single Oxygen Atom Works (O) • Final electron acceptor

– Removes two electrons from complex IV

– Reacts with 2 H⁺ to produce H₂O

• BUT WE BREATH IN O₂ NOT A SINGLE O

• So for every O₂ molecule – Pulls a total of 4 electrons

through the electron transport chain

– 2 H₂O molecules are produced

• Pulling 4 electrons from complex IV triggers a chain reaction between other complexes!!

What happens in this chain of reactions?

• Starts with O₂• Pulls electrons

through the chain of complexes

• NADH is least electronegative but contains most free energy

• O₂ has highest electronegativity but contains least amount of free energy

Proton Gradient• Electron Transport from

NADH or FADH₂ to O₂ does not produce any ATP!!

• What does?• Proton Gradient

– Transport of H⁺ ions across the inner mitochondrial membrane from the matrix into the inter-membrane space

• Creates• Proton-Motive Force

– Chemical gradient (difference in concentrations)

– Electro potential gradient is created (because of the positive charge on Hydrogen atom)

Proton Gradient

Chemiosmosis• The ability of

cells to use the proton-motive force to do work

• Synthesizes ATP using electrochemical gradient

• Uses ATP synthase enzyme– ATP is

synthesized using oxidative phosphorylation

34 ATP are Produced!

Oxidative Phosphorylation• Relies on ATP

synthase– Forms a channel

which H⁺ ions can pass freely

– H⁺ ions cause the synthase to rotate harnessing potential energy to synthesize ATP

NADH from Glycolysis• NADH produced during glycolysis is in cytosol – Transported into mitochondria via two shuttle

systems• Malate-aspartate shuttle• Glycerol-phosphate shuttle

NADH and FADH₂• For every NADH that is oxidized

– About 3 ATP are synthesized– 10 NADH x 3 ATP = 30 ATP – NADH is derived from vitamin niacin

• For every FADH₂– About 2 ATP are synthesized– 2 FADH₂ x 2 ATP = 4 ATP– FADH₂ is derived from vitamin riboflavin (B₂)

• Total of 34 ATP synthesized by electron transport chain

• NADH and FADH₂ are involved in REDOX reactions

• Considered Cosubstrates

Efficiency of Cellular

Respiration

Efficiency of Cellular Respiration• 38 ATP produced • Hydrolysis of ATP yields 31kJ/mol• 31 kJ/mol x 38 ATP = 1178 kJ/mol• Oxidation of Glucose contains 2870 kJ/mol of

energy

Only 41% of the energy in oxidation of glucose in converted into ATPThe rest is lost as thermal energy

%41%100)/2870(

)/1178(x

molkJ

molkJ

Cells that need a constant supply of ATP• Brain cells, muscle cells

– Need burst of ATP during periods of activity

• Creatine phosphate pathway– Immediate source of energy – Creatine phosphate splits (high energy)– Donated directly to ADP to re-form ATP– Stored within cell (3 to 5 times more

than ATP)– Provides enough energy for minute

walk or short distance sprint

creatine + ATP → creatine phosphate + ADP

creatine phosphate → creatine + ATP

Cellular Respiration • Regulated – Feedback inhibition

• Enzyme used – Phosphofructokinase

• Inhibited by– High levels of ATP– High levels of citrate

• Activated by– High levels of ADP– High levels of AMP

• Glucose– Stored as glycogen