Chapter 9

Cellular Respiration

Some intermediates “feed into” other pathways Catabolic pathways provide building block

molecules and energy for anabolic pathways

Metabolic Pathways

energy

energy

Participants in Metabolic Pathways

NAD+

hexokinase

phosphoglucose isomerase

phosphofructokinase

Reactant (substrate)

Intermediates

Product

Participants in Metabolic Pathways

NAD+

hexokinase

phosphoglucose isomerase

phosphofructokinase

Enzymes…

CofactorsCoenzymes

Cellular Respiration & Photosynthesis

PHOTOSYNTHESIS“energy-capturing”

CELLULAR RESPIRATION“energy-releasing”

6O2 + 6CO2 + 6H2O

SOLARENERGY

C6H12O6

ATPchemical energy

glucose

Which process is exergonic?

Which process is anabolic?

Glucose:Hub of Energy Processing in Cells

Glucose production (anabolism) and

storage

Glucose:Hub of Energy Processing in Cells

Breakdown of glucose (catabolism) for energy

Cellular Respiration

Cellular Respiration – process by which cells produce ATP from a nutrient molecule (usually glucose) with high potential energy

Step-wise release of energy from glucose Requires O2

Glucose is broken down (catabolized) to CO2 and H2O

Glucose is oxidized to CO2

Exergonic process (net) Released energy is used to make ATP (from ADP + Pi)

• 4 connected pathways– Glycolysis– Pyruvate processing

(prep rxn)– Citric acid (Krebs)

cycle– Electron transport

chain/chemiosmosis

• 2 types of electron carriers

• 2 compartments• 2 types of ATP synthesis

Cell Respiration…

ATP Cycle: Renewing Supplies of ATP

Energy from EXERGONIC

reactions(e.g. cellular respiration)

Energy for ENDERGONIC

reactions(e.g. protein

synthesis, muscle contraction)

Making ATP

ATP is produced using the energy stored in organic molecules (chemical energy; potential energy) such as glucose

One way of transferring

energy is through the transfer of electrons

Electrons and

energy transferred to molecule

B

Methods of Producing ATP

Substrate-Level Phosphorylation – enzyme catalyzes transfer of phosphate group from phosphorylated substrate to ADP (to make ATP)

Oxidative Phosphorylation (Electron Transport & Chemiosmosis) – oxidation of NADH and FADH2 and electron transport produces proton gradient, which drives ATP synthesis (phosphorylation of ADP)

Enzyme

ADPATP

Phosphorylatedsubstrate

Methods of Producing ATP

substrate-level phosphorylation

oxidative phosphorylation

Cytosol

Electrons

Electron transport chain

Glycolysis

Steps 1-3 (energy investment) Start with one glucose (hexose

sugar) Rearrange structure Add phosphate groups

Steps 4 & 5 (sugar splitting) Split hexose in half Both halves used in subsequent

rxns Steps 6-10 (energy harvest)

Rearrange structure & remove phosphates

End with two pyruvates (3-carbon organic acid)

Glycolysis – What goes in and what comes out

What comes out:

What goes in:

All 10 reactionsof glycolysisoccur in cytosol

Glycolysis begins with anenergy-investment

phase: 2 ATP 2 ADP

Enzyme Glucose-6-phosphate

Fructose-6-phosphate

Fructose-1,6-bisphosphate

Glucose

Pyruvate

The “2” indicates that glucosehas been split into two 3-carbonsugars (only one is shown)

During the energy payoff phase, 4 ATPare produced for a net gain of 2 ATP

Substrate-level phosphorylations

Glycolysis – What goes in and what comes out

GlycolysisTracking Carbon and Energy Carbon

Inputs: 1 glucose (6-C) Outputs: 2 pyruvate (3-C each)

Energy Inputs:

potential energy contained in chemical bonds in glucose 2 ATP

Outputs: potential energy in bonds in pyruvate (less than in glucose) 4 ATP (Net: 2 ATP) 2 NADH (carry electrons/energy)

Regulation of Glycolysis

Glucose Glucose-6-phosphate

Fructose-6-phosphate

Fructose-1,6-bisphosphate

PFK

Committed Step• catalyzed by phosphofructokinase (PFK)• PFK is inhibited by ATP

ATP

Feedback Inhibition

Feedback Inhibition – an enzyme in a metabolic pathway is inhibited by the product of the reaction sequence

Why is feedback inhibition beneficial?

Allostericsite

Fructose-1,6-bisphosphateat active site

ATP/ADP atactive site

Regulation of Glycolysis: PFK

Fructose-6-phosphate

Fructose-1,6-bisphosphate

PFK

ATP

PFK has two binding sites for ATP… Active site – ATP as substrate Allosteric site – ATP as allosteric

inhibitor

Cellular Respiration or Fermentation?

glucose

2 pyruvate

6 CO2 + 6 H2O 2 ethanol + 2 CO2 or 2 lactate

glycolysis 2 ATP

No O2O2cellular respiration fermentation

~25 ATP

Cellular Respiration or Fermentation?

Cellular respiration

If electron acceptor(such as oxygen)

is present

If electron acceptor(such as oxygen)is NOT present

Inefficient! Do not completely oxidize glucose Only utilize glycolysis Only make 2 ATP per glucose Regenerate NAD+

Do not produce enough energy to sustain large, active, multicelled organisms

Fermentation Pathways

Fermentation Pathways

First step - Glycolysis Glucose 2 pyruvate Generates 2 ATP and 2 NADH

Lactic Acid Fermentation 2 Pyruvate 2 Lactate Regenerates 2 NAD+

Alcoholic Fermentation 2 Pyruvate 2 Ethanol (Ethyl

Alcohol) + 2 CO2

Regenerates 2 NAD+

No intermediate;pyruvate acceptselectrons from NADH

2 Acetylaldehyde

2 Pyruvate

2 Pyruvate

2 Lactate

2 Ethanol

Pyruvate Processing

Inputs: 2 Pyruvate 2 Coenzyme A 2 NAD+

Outputs: 2 Acetyl CoA 2 NADH 2 CO2

Location: mitochondiral matrix

Pyruvate Processing

Coenzyme A – enzyme cofactor that acts as acetyl group “carrier” when acetyl group has bound CoA, it is “activated” (easily

transferred to acceptor molecule)

acetyl group“activated”

Coenzyme A

Pyruvate ProcessingTracking Carbon and Energy Carbon:

Inputs: 2 pyruvate (3-C each)

Outputs: 2 acetyl groups (carried by Coenzyme A) (2-C each) 2 CO2

Energy Inputs:

potential energy contained in bonds in pyruvate Outputs:

potential energy in bonds in acetyl groups (carried by Coenzyme A)

2 NADH (carry electrons/energy)

Regulation of Pyruvate Processing

Pyruvate conversion to Acetyl CoA is catalyzed by the pyruvate dehydrogenase complex; key regulatory point in glucose oxidation

Inhibited by: (feedback inhibition) ATP Acetyl CoA NADH

Activated by: AMP CoA NAD+

pyruvate dehydrogenase

complex

Citric Acid Cycle Citrate is

oxidized in a step-wise manner

Electrons (energy) transferred to NAD+ and FAD

Citric Acid CycleTracking Carbon and Energy Carbon:

Inputs: 2 Acetyl groups (carried by Coenzyme A) (2-C each)

Outputs: 4 CO2

Energy Inputs:

potential energy contained in bonds of acetyl groups Outputs:

2 ATP (substrate-level ATP synthesis) 6 NADH (carry electrons/energy) 2 FADH2 (carry electrons/energy)

So Far…summary of steps 1-3

Glucose has been fully oxidized to 6 CO2

Potential energy released from glucose has been used to generate 4 ATP (substrate-level ATP synthesis) and…

Electrons (energy) released from glucose during oxidation have been used to reduce: 2 FAD 2 FADH2

10 NAD+ 10 NADH Glucose(reduced)

6 CO2

(oxidized)

NAD+ and FADH(oxidized)

NADH and FADH2

(reduced)

This is were the energy is!

Cellular Respiration: Overview

Electron Transport Chain and Chemiosmosis: Summary

Electrons (carried by NADH and FADH2) are delivered to the electron transport chain (ETC)

Electrons are passed down the ETC to oxygen – undergo redox reactions; release energy

Released energy is used to pump protons (H+) across inner mitochondrial membrane; generates a proton gradient

Energy in gradient (proton-motive force) is used to drive synthesis of ATP (via chemiosmosis) by ATP synthase

Electron Transport Chain - Overview

Membraneof cristae

ComplexI

Intermembranespace

ComplexII

Mitochondrialmatrix

Complex I Complex II Complex III Complex IV

ComplexIII

ComplexIV

The electron transportchain occurs in theinner membrane of themitochondrion(membranes of cristae)

Chemiosmosis- Overview

Intermembranespace

Mitochondrialmatrix

Fo unit

Stator Rotor

F1 unit

Electron Transport Chain

Electrons from NADH and FADH2 are passed down ETC to O2 (final electron acceptor); generates H+ gradient

http://www.youtube.com/watch?v=xbJ0nbzt5Kw&feature=related

Chemiosmosis

Proton (H+) electrochemical gradient drives ATP synthesis via ATP synthase

Proton-Motive Force – Energy associated with movement of H+ ions down their concentration gradient across the IMM

Chemiosmosis – production of ATP via a proton gradient

Cellular Respiration: Overview

Glycolysis Pyruvate Processing and Citric Acid Cycle

Glucose

Acetyl CoA

Pyruvate

Oxaloacetate

In each of these drops,energy is transferred toenergy-storing moleculesATP, NADH, and FADH2

Series of chemical reactions,

each catalyzed by

a specific enzyme

Cellular respiration is a step-wise release of

energy from glucose

Disruption of Chemiosmosis by Poisons

Electron Transport Blockers Cyanide CO (carbon monoxide)

Uncoupler DNP (dinitrophenol)

Disruption of Chemiosmosis by Poisons

Electron Transport Blockers Cyanide CO (carbon monoxide)

Uncoupler DNP (dinitrophenol)

Anaerobic Respiration

What is the difference between anaerobic fermentation (previous slides) and anaerobic respiration? Anaerobic respiration involves the citric acid cycle and an

electron transport chain, but this ETC uses a different final electron acceptor – e.g. NO3

- , SO42-, S, or Fe3+.

Most species that perform anaerobic respiration are prokaryotes that live in environments devoid of O2.

For more information, including the ecological and economic significance of these organisms, see Wikipedia: anaerobic respiration.

Big Picture