How do cells extract energy from glucose? Cellular Respiration How do cells extract energy from glucose?

Where did Chuck Norris get all that energy from? Cellular Respiration Where did Chuck Norris get all that energy from?

What is Cellular Respiration? An aerobic process (requires oxygen) Uses chemical energy from glucose to make ATP The chemical energy stored in ATP can be used throughout the cell O2 glucose 1 ATP 36 cellular resp.

Four Main Stages Glycolysis Pyruvate Oxidation Krebs Cycle Anaerobic / In cytosol breaks glucose (6C) into two pyruvate (3C) Generates 2 ATP and 2 NADH Pyruvate Oxidation Pyruvate converted to acetyl CoA Oxidative decarboxylation Generates NADH (inside mitochondria) Krebs Cycle Within mitochondrial matrix Two more oxidative decarboxylation reactions Generates ATP, NADH and FADH2 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

Key Reactions substrate level phosphorylation An enzyme mediated reaction that directly produces ATP oxidative decarboxylation The formation of CO2 coupled with the formation of NADH, FADH2 or ATP oxidative phosphorylation Use of a proton gradient to generate ATP using ATP synthase

Do Cells NEED Mitochondria? It is possible to generate relatively small amounts of ATP relying exclusively on the reactions in the cytoplasm Fermentation is essentially glycolysis, however, the final products are slightly modified We will return to this process in detail after learning about cellular respiration

Cellular Respiration Equation General Formula O2 glucose CO2 H2O H+ Energy C6H12O6 + 6 O2  6 CO2 + 6 H2O + energy The process begins immediately when glucose enters the cytoplasm. Here, there are enzymes waiting to begin the process of glycolysis.

Glycolysis I The “investment” period ATP is USED to activate glucose This is accomplished via phosphorylation reactions Adding a phosphate group from ATP

Numbering The Carbons glucose In order to keep track of how glucose is modified and rearranged during glycolysis we number each carbon C O 6 5 glucose 1 4 3 2

Glycolysis (I) glucose glucose-6-phosphate fructose-6-phosphate fructose-1-6-bisphosphate 2 molecules of G3P (glyceraldehyde-3-phosphate) P P P C O C O P C O P P P C O P P C P C P

Glycolysis (I) glucose glucose-6-phosphate fructose-6-phosphate fructose-1-6-bisphosphate 2 molecules of G3P (glyceraldehyde-3-phosphate) ATP ADP P C O C O P ATP ADP C O P P C P C P

Glycolysis (II) The “pay-off” period ATP and NADH (a temporary high energy carrier) are PRODUCED during glycolysis II By the end of glycolysis II, glucose has been broken down to two 3 carbon compounds called pyruvate (pyruvic acid)

Glycolysis (II) G3P glyceraldehyde-3-phosphate PGAP 1,3-bisphosphoglycerate PGA 3 - phosphoglycerate PEP phosphoenolpyruvate Pyruvate C P C P NAD NAD Pi Pi NADH NADH C P P P P P P C P P C P H2O H H2O H C P P P P P P C

Glycolysis (II) G3P PGAP PGA PEP Pyruvate glyceraldehyde-3-phosphate 1,3-bisphosphoglycerate PGA 3 - phosphoglycerate PEP phosphoenolpyruvate Pyruvate C P C P NADH NADH C P P ATP ATP C P H2O H H2O H C P C ATP ATP C

2 2 Summing Up Glycolysis Used 2 ATP, but made 4 ATP Net Gain: and Glycolysis I Glycolysis II Used 2 ATP, but made 4 ATP Net Gain: and ATP 2 NADH 2 (high energy molecule)

Glycolysis: Overall Reaction C6H12O6 + 2ADP + 2P + 2NAD+  2C3H4O3 + 2NADH + 2ATP glucose (6C) pyruvate (3C) Notice: There is no oxygen used in glycolysis. It is an anaerobic process O2

The POWER HOUSE! Glycolysis (in the cytosol) produces only 2 ATP per glucose This means that 34-36 more ATP are made in the mitochondria! How does pyruvate get in there and what happens inside!? nucleus cytosol ATP ATP mitochondria ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP ATP

Mitochondria On a separate page draw a labeled diagram of a mitochondrion outer membrane inner membrane matrix Kreb’s H+ intermembrane space ETC cristae

Mitochondria in 3D

Electron Micrograph of Mitochondria

Pyruvate Oxidation pyruvate translocase

multi-enzyme pyruvate dehydrogenase complex Pyruvate Oxidation NAD+ NADH Decarboxylation Oxidation Attachment (of coenzyme A) ENERGY CO2 multi-enzyme pyruvate dehydrogenase complex

multi-enzyme pyruvate dehydrogenase complex Pyruvate Oxidation NADH Acetyl-CoA multi-enzyme pyruvate dehydrogenase complex Decarboxylation Oxidation Attachment (of coenzyme A)

Pyruvate Oxidation Pyruvate enters the mitochondria via a protein carrier called pyruvate translocase Once inside, a multi-enzyme pyruvate dehydrogenase complex converts pyruvate into acetyl CoA via an oxidative decarboxylation Acetyl CoA can enter Krebs cycle

steps 1 and 2 together are an oxidative decarboxylation Pyruvate Oxidation In the pyruvate oxidation, for each molecule of pyruvate: CO2 1 is released and NADH 1 is produced steps 1 and 2 together are an oxidative decarboxylation

steps 1 and 2 together are an oxidative decarboxylation Pyruvate Oxidation Remember: There are 2 pyruvates produced for each glucose. Therefore, for each glucose: CO2 1 is released and NADH is produced CO2 2 are released and NADH are prodcued X2 steps 1 and 2 together are an oxidative decarboxylation

Krebs / Citric Acid Cycle Pyruvate Oxidation Krebs Cycle

Krebs Cycle In the Krebs Cycle for each molecule of pyruvate: CO2 2 are released and NADH 3 ATP 1 FADH2 1 are produced

X2 4 6 2 2 3 1 Krebs Cycle NADH FADH2 NADH FADH2 Remember: There are 2 pyruvates produced for each glucose. Therefore, for each glucose: CO2 4 are released NADH 6 and FADH2 2 ATP are produced CO2 2 are released NADH 3 and FADH2 1 ATP are prodcued X2

pyruvate oxidation & Krebs Cycle The Story So Far pyruvate oxidation & Krebs Cycle glycolysis glucose 1 C – C – C pyruvate 2 CO2 6 (6C) (3C) (1C) ATP 4 ATP 2 NADH 10 NADH 2 FADH2 2

2 2 2 6 4 10 2 The Story So Far Totals Glycolysis Tracking High Energy Molecules Metabolic Process ATP Produced High Energy Molecules Glycolysis Pyruvate Oxidation (x2) Krebs Cycle (x2) Totals ATP 2 NADH in cytosol NADH 2 ATP 2 NADH 6 FADH2 ATP 4 NADH 10 FADH2 2

Oxidative Phosphorylation NADH and FADH2 are in their high energy reduced form with an extra pair of electrons These electrons are donated to carrier proteins in the Electron Transport Chain (ETC). The electrons are passed from protein to protein via redox reactions The energy from the electrons is used to pump protons (H+) into the intermembrane space of the mitochondria

Electron Transport Chain not part of the ETC C Cristae UQ NADH reductase Cytochrome b1c1 Cytochrome c Cytochrome c oxidase Ubiquinone ATP Synthase Electron Carriers: 1. Complex I [protein] 2. Ubiquinone [non-protein] 3. Complex III 4. Cytochrome c 5. Complex IV [protein]

Electron Transport Chain Cristae UQ To pass electrons along ETC, each carrier is reduced (gains electrons) then oxidized (donates electrons)

Electron Transport Chain Cristae UQ NAD+ NADH NADH donates a pair of electrons to NADH reductase electrons continue along ETC via sequential oxidations and reductions

Electron Transport Chain Cristae UQ FADH2 FADH2 donates a pair of electrons to coenzyme Q electrons also continue along ETC

Electron Transport Chain Cristae UQ FADH2 donates a pair of electrons to coenzyme Q electrons also continue along ETC

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

For each NADH, 6 H+ are pumped across the mitochondrion inner membrane Cristae UQ H2O H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ O2 For each NADH, 6 H+ are pumped across the mitochondrion inner membrane Oxygen is the final electron acceptor and is converted to H2O

H+ H+ H+ C Cristae UQ H2O H+ H+ H+ H+ H+ H+ H+ FADH2 H+ H+ H+ H+ O2 For each FADH2, 4 H+ are pumped across the mitochondrion inner membrane

The electrochemical proton gradient High Proton Concentration H+ H+ Gradient C Cristae UQ H+ Low Proton Concentration H+ H+ H+ H+ H+ The electrochemical proton gradient (sometimes referred to as the proton motive force)

ATP synthase works a bit like a water mill

H+ H+ H+ H+ H+ H+ H+ C Cristae UQ ATP 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 The movement of ions along their concentration gradient across a semi-permeable membrane is known as chemiosmosis.

H+ H+ H+ H+ H+ H+ H+ C Cristae UQ ATP ATP ATP H+ H+ H+ H+ H+ H+ 1 ATP is generated for each proton pair flowing through ATP synthase. Pumps H+ 6 3 NADH

H+ H+ H+ H+ H+ H+ H+ C Cristae UQ ATP ATP H+ H+ H+ H+ H+ H+ 1 ATP is generated for each proton pair flowing through ATP synthase. Pumps H+ 4 2 FADH2

The WHOLE process… Cristae C UQ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+

The WHOLE process… Cristae NAD+ NADH C UQ H+ H+ H+ H+ H+ H+ H+ H+ H+

The WHOLE process… Cristae C H2O O2 UQ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+

The WHOLE process… Cristae C ATP ATP ATP UQ H+ H+ H+ H+ H+ H+ H+ H+ H+

The WHOLE process… Cristae C ATP ATP ATP UQ H+ H+ H+ H+ H+ H+ H+ H+ H+

Remember: BEFORE the ETC we had… Summing up ATP Remember: BEFORE the ETC we had… Metabolic Process ATP Produced High Energy Molecules Glycolysis Transition Reaction (x2) (oxidative decarboxylation) Krebs Cycle (x2) Total ATP 2 NADH in cytosol NADH 2 ATP 2 NADH 6 FADH2 ATP 4 NADH 10 FADH2 2

In the Electron Transport Chain Summing up ATP In the Electron Transport Chain Molecules from High Energy Molecules ATP produced in ETC Glycolysis Transition Reaction (x2) Krebs Cycle (x2) Total NADH 2 ATP 4 in cytosol NADH 2 ATP 6 NADH 6 FADH2 2 ATP 22 10 FADH2 2 ATP 32 NADH

2 2 4 + From Glycolysis 2 2 6 6 2 22 10 2 34 32 Summing up ATP Total IN TOTAL Molecules from High Energy Molecules ATP produced in ETC Glycolysis Transition Reaction (x2) (oxidative decarboxylation) Krebs Cycle (x2) Total ATP 2 NADH 2 ATP 4 in cytosol + From Glycolysis ATP 2 NADH 2 ATP 6 NADH 6 FADH2 2 ATP 22 10 FADH2 2 ATP 34 ATP 32 NADH

2 2 4 + From Krebs Cycle 2 2 6 6 2 22 2 10 2 36 34 Summing up ATP IN TOTAL Molecules from High Energy Molecules ATP produced in ETC Glycolysis Transition Reaction (x2) (oxidative decarboxylation) Krebs Cycle (x2) Total ATP 2 NADH 2 ATP 4 in cytosol + From Krebs Cycle ATP 2 NADH 2 ATP 6 NADH 6 FADH2 2 ATP 22 ATP 2 10 FADH2 2 ATP 36 ATP 34 NADH

glucose + oxygen carbon dioxide + water + energy Overall Reaction glucose 1 CO2 6 glucose CO2 NAD+ 10 FAD 2 NADH 10 FADH2 2 NAD+ 10 FAD 2 Catalysts ATP 36 Energy H2O H+ H2O H+ O2 O2 glucose + oxygen carbon dioxide + water + energy

glucose + oxygen carbon dioxide + water + energy Overall Reaction Phase (location) Glycolysis (cytosol) Transition Reaction (mito.) Kreb’s Cycle (mito.) ETC (mito.) glucose 1 CO2 6 some NAD+ 10 FAD 2 ATP 36 some H2O H+ O2 glucose + oxygen carbon dioxide + water + energy

Alternate Metabolic Pathways

Fermentation When oxygen is NOT available, cells can metabolize pyruvate (derived from glucose) by the process of fermentation. Two Types (i) alcohol fermentation: pyruvate is reduced to ethyl alcohol and CO2; occurs in yeast cells (ii) lactic acid fermentation: pyruvate reduced to lactic acid in muscle cells