Lecture 11

Textbook Notes — Chapter 9 continued

9.3 Processing Pyruvate to Acetyl CoA

• pyruvate processing is a series of reactions that convert pyruvate to acetyl CoA in the mitochondrial matrix in eukaryotes or the cytosol of prokaryotes

  • NADH and CO2 are produced

• the pyruvate dehydrogenase complex is inhibited when it is phosphorylated by ATP

  • it speeds up in the presence of reactants and slows down in the presence of products

• pyruvate, NAD+, CoA → CO2, NADH, acetyl CoA

• feedback inhibition shuts down pyruvate dehydrogenase when the products of pyruvate processing (NADH and acetyle CoA) or product of glycolysis (ATP) are abundant

9.4 The Citric Acid Cycle: Oxidizing Acetyl CoA to CO2

• citric acid cyle is an 8-step reaction cycle in the matrix of mitochondria or the cytosol of prokaryotes

  • begins with acetyle CoA and produces FADH2, NADH, and ATP/GTP

  • at the end, all of the carbons from glucose are completely oxidized to CO2

• certain enzymes in the citric acid cycle are inhibited when NADH or ATP binds to them

• generates 3 NADH, 1 FADH2, 1 ATP/GTP

9.5 Electron Transport and Chemiosmosis

• the electron transport chain resides in the inner membrane of mitochondria or the plasma membrane of prokaryotes

• consists of a series of electron acceptors that vary in their redox potential, starting with the oxidation of NADH and FADH2, ending with the reduction of a terminal electron acceptor, like O2

• the change in energy that accompanies the redox reactions is used to move H+ across the inner mitochondrial membrane, creating an electrochemical gradient

• ATP production is couple to ETC by oxidative phosphorylation

• the potential energy stored in the proton gradient built up by the ETC is used to spin components of the ATP synthase to produce ATP

  • makes most of the ATP made by cellular respiration

Lecture Slides

• pH of mitochondria intermembrane space = 7, due to porins

Phase 2: Pyruvate Oxidation and Krebs Cycle

pyruvate oxidation

• 2 pyruvate gets oxidized (exergonic) to 2 acetyl CoA

• the CO2 splitting off the pyruvate is exergonic enough to pay for:

  • covalently bonding a coenzyme A (CoA — SH)

  • and reduction of NAD+ to NADH

krebs cycle

• all 8 reactions of the citric acid cycle occur in the mitochondrial matrix, outside the cristae

• the citric acid cyel runs twice for each glucose molecule oxidized

• in each turn of the cycle, two carbons get converted to CO2

• each reaction is catalyzed by a different enzyme

• produces 2 NADH, one ATP/GTP, and one FADH2 for each acetyl CoA, so 4 NADH, 2 ATP/GTP, and 2 FADH2

Net results of Phase 1 (glycolysis) and Phase 2 (pyruvate oxidation and Krebs cycle) for each glucose

• glucose → 2 pyruvate + 2 NADH + 2 ATP (cytosol)

• 2 pyruvate → 2 Acetyl CoA + 2 NADH + 2 CO2 (mitochondrial matrix)

• 2 Acetyle CoA into Citric Acid Cycle → 6 NADH + 2 FADH2 + 4 CO2 + 2 ATP (mitrochondrial matrix)

• total: 10 NADH, 2 FADH2, 4 ATP

Problems at end of Krebs Cycle

1. still haven’t replaced NAD+; more NADH has been made

2. FADH2 needs to be re-oxidized

3. still haven’t transferred energy carried by cofactors to ATP

why dependent on oxygen

• aerobic respiration requires oxygen, but Krebs Cycle itself does not

• because krebs cycle is coupled to the third pathway which does require oxygen — the electron transport chain

Electron Transport Chain

• NADH drops off its electrons at complex I, turning into NAD+

  • pays for energy to move H+ forcibly into intermembrane space

• FADH2 drops off its electrons at complex II, turning into FAD

• CoQ — mobile electron carrier, carries electrons from complex I, II → complex III

• Cyt c — carries electrons from complex III → complex IV

• O2 is the final electron accepter, turning into H2O

  • 2 * (2H+ + ½ O2 + 2e- → H2O)

• at the end, ATP synthase, which is not a part of the ETC, lets H+ flow back into the matrix, using that flow to convert ADP → ATP

The Electron Transport Chain

• NADH passes its electrons (and is re-oxidized to NAD+) to the first carrier in the membrane

  • this ends NAD+/NADH’s involvement, and NAD+ is now free to participate in another redox reaction

• first electron carrier passes to second, second carrier passes to third, and so on

  • because carriers are at successively lower energy levels, energy is released when the electrons are passed (releasing energy, never increasing in energy)

  • this energy is used to pump protons across the membrane

    • a proton gradient (aka electrochemical gradient) is produced

• last electron carrier passes electrons to oxygen, which combines with protons to form water

  • now we’ve accounted for the CO2 (krebs) and H2O (etc)

• FADH2 also joins the party, but passes its electrons to a carrier down the line

  • bypassing complex I

  • deposits at complex II, which is not transmembrane, so it doesn’t contribute as much as NADH → NAD+

  • not as many protons pumped across the membrane

    • less of a contribution to the overall electrochemical gradient

Result of ETC

• regenerated cofactors and built gradient, but no ATP

• intermembrane space (pH = 7) has 10 times more H+ than the mitochondrial matrix (pH = 8)

• the proton gradient is unstable, the protons want back in, so ATP synthase utilizes this potential energy, turning into kinetic energy used for oxidative phosphorylation, converting ADP to ATP

at end of oxidation of glucose

• all energy from breakdown of glucose (not lost as heat) is ultimately used to make ATP:

  • glucose + 6 O2 → 6 CO2 + 6 H2O

• theoretical ATP production from full oxidation of glucose = 36 ATP

  • 2 ATP from glycolysis

  • 2 NADH from glycolysis (x2 ATP each) = 4 ATP

  • 2 GTP from TCA cycle = 2 ATP

  • 8 NADH from TCA cycle (x 3 ATP each) = 24 ATP

  • 2 FADH2 from TCA cycle (x 2 ATP each) = 4 ATP