Cellular Respiration

The BIG PICTURE ATP

◦ structure, role & importance of this molecule Importance of step-wise oxidation (through

glycolysis & Krebs Cycle) Substrate-level phosphorylation vs. oxidative

phosphorylation Electron transport chain & its link to chemiosmosis

◦ Gradient◦ ATP synthase

Importance/role of fermentation Evolutionary significance

Important Concepts & Objectives

Overall Goal:◦ Converting organic molecules [ie. sugar] into usable

cellular energy [ATP] Exchanging foreign currency

Endergonic OR exergonic reaction?◦ Endergonic Reaction

Putting IN energy to form bonds Remember that BONDS represent ENERGY

◦ Exergonic Reaction Breaking bonds, RELEASING energy

Overall Equation:◦ C6H12O6 + O2 CO2 + H2O + ATP

The BIG Picture

ATP is the main energy currency of the cell

Made of 3 major components:◦ Adenine

Nitrogenous base◦ Ribose

Sugar◦ 3 phosphate groups

“popping off” the last phosphate group releases energy to perform cellular work

ATP Structure

ATP Structure

Oxidation◦ The LOSS of electrons

The compound becomes more POSITIVE Reduction

◦ The GAIN of electrons The compounds becomes more NEGATIVE

◦ WHY? Cellular respiration is a series of

oxidation/reduction reactions that uses the transfer of electrons (e-) to perform work◦ NB: electrons (e-) and protons (H+) travel together

Oxidation/Reduction

Organic molecules that have LOTS Of hydrogen are excellent fuels◦ These bonds have lots of “hilltop” electrons

whose energy can be released as the electrons “fall” down an energy gradient towards oxygen

◦ SLOW and STEP-WISE Why? Think gasoline!

Organic Molecules as Fuel

As electrons move closer to oxygen (highly electronegative), chemical energy is released that can be put to work

Glucose NADH Electron Transport Chain Oxygen

Least electronegative Most electronegative

Activation energy is required to start this process◦ Enzymes help to lower this EA

Organic Molecules as Fuel

Cellular Respiration: An Overview

“glucose-breaking” Occurs in the CYTOSOL Breaks glucose (6-C)

into pyruvate (3-C)◦ Requires an investment

of 2 ATP to do this ENERGIZED

Does NOT require oxygen (anaerobic)

Diagram

Glycolysis

Produces 4 ATP through substrate-level phosphorylation◦ Occurs when an enzyme transfers a phosphate

group directly from a substrate molecule to ADP ADP + P ATP

◦ Net gain of 2 ATP Also produces 2 NADH

◦ (electron carriers)◦ Will go to ETC - stay tuned!

Glycolysis

Net Gain In Glycolysis◦ 2 ATP

-2 ATP (energy investment – to start the process)+4 ATP (substrate level phosphorylation)

2 ATP• 2 NADH• Electron carriers• Will be used to make ATP later

• 2 molecules of pyruvate (3-C each)• Still holds MOST of the energy in the original glucose

molecule

Glycolysis

Cellular Respiration

There are 2 pyruvate molecules (3-C each) left after glycolysis◦ If oxygen is PRESENT, the pyruvate enters the

mitochondrion◦ The oxygen is like the “key” that unlocks the mitochondrion

Before entering the Krebs Cycle, pyruvate is converted to Acetyl CoA◦ CO2 is released as a waste

product◦ NADH (electron carrier) is produced◦ Coenzyme A is added

Makes it very reactive

The Citric Acid/Krebs Cycle

The Krebs Cycle functions as a metabolic “furnace” that transfers most of the rest of the energy from Acetyl CoA (from pyruvate) to ATP, NADH, and FADH2

The Citric Acid/Krebs Cycle

Acetyl CoA (2-C) joins with oxaloacetate (4-C) in the first step, creating citrate (6-C)◦ Carbon dioxide is released (2

molecules)◦ NADH is formed◦ FADH2 is formed◦ ATP is formed

Substrate level phosphorylation◦ Oxaloacetate is regenerated

CYCLE

The Citric Acid/Krebs Cycle

The Citric Acid/Krebs Cycle

Yield per pyruvate molecule◦ 4 NADH – electron carrier◦ 1 FADH2 – electron carrier◦ 1 ATP

Yield per glucose molecule◦ 8 NADH◦ 2 FADH2

◦ 2 ATP CO2 released as a waste product

The Citric Acid/Krebs Cycle

What we REALLY need is ATP – the energy currency of the cell!

Where is most of the energy from the original glucose molecule stored?◦ Only 4 ATP so far

2 glycolysis & 2 Krebs Cycle (both substrate-level)

◦ The energy is stored in the NADH & FADH2 – electron carriers

The electron transport chain and chemiosmosis allow us to convert the energy in NADH & FADH2 into ATP

But what now??

The electrons from NADH and FADH2 are passed from one electron acceptor (cytochrome) to another◦ Cytochromes are (mostly) proteins embedded in

the inner mitochondrial membrane, folded into cristae

Why??

Electron Transport Chain

Diagram:

NADH “donates” its electron at the BEGINNING of the electron chain, while FADH2 “donates” its electron further on down the chain

Each electron acceptor (cytochrome) is more electronegative (GREEDY) than the one before it

Oxygen is the FINAL (and most electronegative) electron acceptor◦ This forms WATER

Electron Transport Chain

As electrons “fall” down the ETC, the energy they lose along the way is used to pump H+ out of the mitochondrial matrix and into the intermembrane space◦ Creates a gradient◦ Why does this require energy?

Diagram

Chemiosmosis

As the H+ come back through the membrane (to attempt to restore equilibrium), ATP synthase uses this energy to join ADP + P to form ATP◦ ATP synthase functions like a waterwheel/turbine◦ This is oxidative phosphorylation

Each NADH electron pumps enough protons to create 3 ATP Because FADH2 gives its

electron further down the ETC, it can only generate 2 ATP

Chemiosmosis

Glycolysis:◦ 2 ATP◦ 2 NADH 4 ATP

(NADH from glycolysis makes fewer ATP than those from Krebs)

Krebs Cycle◦ 2 ATP◦ 8 NADH 24 ATP (ETC)◦ 2 FADH2 4 ATP (ETC)

Total:◦ 6 ATP + 30 ATP 36 ATP (approx.)

ATP Bookkeeping: Keeping Track

C6H12O6 + O2 CO2 + H2O + ATP

Cellular Respiration

But what if oxygen is NOT available?◦ Glycolysis can occur whether or not oxygen is

present 2 ATP (from substrate-level phosphorylation in

glycolysis) are better than 0◦ Fermentation (anaerobic respiration) works by

allowing glycolysis to continue

Anaerobic Respiration

Cellular Respiration

Glycolysis Review: 2 NAD+ 2 NADH

Glucose 2 pyruvate(C-C-C-C-C-C) (C-C-C) (C-C-C)

2 ADP + P 2 ATP

BUT◦ If you run out of NAD+ to take the electrons,

glycolysis would have to stop Then, ZERO ATP would be made

◦ Fermentation solves this problem by regenerating NAD+

Anaerobic Respiration

Anaerobic Respiration Alcoholic

Fermentation◦ Occurs in PLANTS and

YEAST◦ 2 step process

Carbon dioxide is released from pyruvate (3-C), forming acetaldehyde (2-C)

Acetaldehyde is reduced by NADH (gains an electron), forming ethyl alcohol (ethanol)

NAD+ is regenerated, thereby allowing glycolysis to continue

◦ Used to produce alcoholic beverages & bread

Anaerobic Respiration Lactic Acid

Fermentation◦ Occurs in ANIMALS◦ 1-step process

Pyruvate is reduced by NADH (gains an electron), forming lactic acid

◦ NAD+ is regenerated, thereby allowing glycolysis to continue

◦ Occurs in muscle cells, causing muscle pain and fatigue

The Evolutionary Significance of Glycolysis◦ Glycolysis is the most widespread metabolic

pathway◦ Does not require oxygen◦ Occurs in cytosol, not in membrane-bound

organelles

Cellular Respiration