Cellular Respiration How do cells extract energy from

Cellular Respiration How do cells extract energy from glucose?

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

What is Cellular Respiration? • Cellular respiration – An aerobic process (requires oxygen) O 2 – Uses chemical energy from glucose to make ATP 1 cellular resp. glucose 36 ATP – The chemical energy stored in ATP can be used throughout the cell

Four Main Stages 1. Glycolysis • • • Anaerobic / In cytosol breaks glucose (6 C) into two pyruvate (3 C) Generates 2 ATP and 2 NADH 2. Pyruvate Oxidation • • • Pyruvate converted to acetyl Co. A Oxidative decarboxylation Generates NADH (inside mitochondria) 3. Krebs Cycle • • • Within mitochondrial matrix Two more oxidative decarboxylation reactions Generates ATP, NADH and FADH 2 4. Electron Transport Chain • • Along the inner mitochondrial membrane Uses high energy electrons from NADH and FADH 2 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 CO 2 coupled with the formation of NADH, FADH 2 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 Cglucose Energy 6 H 12 O 6 + 6 O 2 6 CO 2 + 6 H 2 O + energy H+ O 2 CO 2 H+ H 2 O 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 • In order to keep track of how glucose is modified and rearranged during glycolysis we number each carbon C 5 4 C 6 C O glucose C C 3 2 C 1

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

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

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) P C C C NAD C Pi C C NAD Pi NADH P PP PP C C NADH C P P C C P C H C C C H C PGA 3 - phosphoglycerate PEP C C PP P phosphoenolpyruvate P C P PP glyceraldehyde-3 -phosphate 1, 3 -bisphoglycerate P P H 2 O P C PP P H 2 O P C G 3 P PGAP P PP C P P PP P C

Glycolysis (II) P C C C G 3 P P NADH C C C P P C C C 1, 3 -bisphoglycerate ATP P H PGAP P ATP glyceraldehyde-3 -phosphate C C C PGA P H 3 - phosphoglycerate H H 2 O P C C C H C ATP PEP phosphoenolpyruvate ATP Pyruvate C C C

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

Glycolysis: Overall Reaction C 6 H 12 O 6 + 2 ADP + 2 NAD+ 2 C 3 H 4 O 3 + 2 NADH + 2 ATP glucose (6 C) pyruvate (3 C) Notice: There is no oxygen used in glycolysis. It is an anaerobic process O 2

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

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

Mitochondria in 3 D

Electron Micrograph of Mitochondria

Pyruvate Oxidation p tra yru ns vat loc e as e

Pyruvate Oxidation NAD+ 1)Decarboxylation NADH m ult py i-en hy ruv zym d co rog ate e m en ple a x se de 2)Oxidation 3)Attachment (of coenzyme A) ENERGY CO 2

Pyruvate Oxidation NADH Acetyl-Co. A 1)Decarboxylation m ult py i-en hy ruv zym d co rog ate e m en ple a x se de 2)Oxidation 3)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 Co. A via an oxidative decarboxylation • Acetyl Co. A can enter Krebs cycle

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

Pyruvate Oxidation Remember: There are 2 pyruvates produced for each glucose. Therefore, for each glucose: 12 and steps 1 and 2 together are an oxidative decarboxylation 12 arereleased is 2 X CO 2 prodcued NADH isareproduced

Krebs / Citric Acid Cycle Pyruvate Oxidation Krebs Cycle

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

Krebs Cycle Remember: There are 2 pyruvates produced for each glucose. Therefore, for each glucose: 42 and are released CO 2 2 X 63 1 2 21 FADH NADH 2 prodcued are produced ATP

The Story So Far 1 glycolysis glucose (6 C) 42 ATP 2 pyruvate oxidation & Krebs Cycle C–C– C pyruvate (3 C) 12 NADH 6 CO 2 (1 C) 2 FADH 2

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

Oxidative Phosphorylation • NADH and FADH 2 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 C Cristae UQ Cytochrome c NADH Ubiquinone c oxidase b 1 c 1 reductase Electron Carriers: • 1. Complex I [protein] • 2. Ubiquinone [non-protein] • 3. Complex III • 4. Cytochrome c • 5. Complex IV [protein] ATP Synthase not part of the ETC

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

Electron Transport Chain C Cristae UQ NAD+ NADH 1) NADH donates a pair of electrons to NADH reductase 2) electrons continue along ETC via sequential oxidations and reductions

Electron Transport Chain Cristae C UQ FADH 2 1) FADH 2 donates a pair of electrons to coenzyme Q 2) electrons also continue along ETC

Electron Transport Chain Cristae C UQ 1) FADH 2 donates a pair of electrons to coenzyme Q 2) electrons also continue along ETC

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

H+ H+ H+ Cristae H+ H+ H+ C UQ H+ H+ H 2 O H+ H+ O 2 For each NADH, 6 H+ are pumped across the mitochondrion inner membrane Oxygen is the final electron acceptor and is converted to H 2 O

H+ H+ H+ Cristae H+ H+ H+ C UQ H+ H+ H+ FADH 2 H+ H+ H 2 O H+ H+ H+ O 2 For each FADH 2, 4 H+ are pumped across the mitochondrion inner membrane H+

H+ H+ H+ Concentration High Proton + H+ H+ H+ Gradient H+ Cristae H+ H+ H+ C UQ H+ H+ Concentration Low Proton + 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+ Cristae H+ H+ H+ C UQ ATP H+ H+ H+ • H+ Using the energy stored of in ions the along proton gradient, ATP The movement their is generated usinggradient oxidative phosphorylation: concentration across a semi-permeable is known chemiosmosis. formationmembrane of ATP coupled toasoxygen consumption

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

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

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

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

H+ H+ H+ Cristae H+ H+ H+ C UQ H+ H+ H+ H 2 O H+ H+ H+ O 2 The WHOLE process… H+

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

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

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

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

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

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

Overall Reaction 1 6 glucose 1 02 FAD NAD+ CO 2 1 36 02 FADH NADH ATP Energy H+ O 2 glucose + oxygen 2 1 02 FAD NAD+ Catalysts H+ H 2 O carbon dioxide + water + energy

Overall Reaction Phase (location) 1 glucose 6 Glycolysis (cytosol) CO 2 e 1 02 FAD NAD+ 36 H+ O 2 glucose + oxygen ATP m so Transition Reaction (mito. ) some Kreb’s Cycle (mito. ) ETC (mito. ) H+ H 2 O 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 CO 2; occurs in yeast cells (ii) lactic acid fermentation: pyruvate reduced to lactic acid in muscle cells