Lecture 17: Cellular Respiration [Citric Acid Cycle and Oxidative Phosphorylation]

What is the electron transport chain?

-A collection of molecules [mostly proteins] embedded in the inner membrane of the mitochondrion in eukaryotic cells [plasma membrane in prokaryotic cells] -Formation of cristae in mitochondrion increase surface area --> Space for thousands of copies of each component of the electron transport chain in a mitochondrion -Electrons [from NADH or FADH2] move from a less electronegative [lower affinity for electrons] electron carrier to a more electronegative electron carrier down the chain RELEASING free energy

ATP synthase

-A protein of which there are many copies of in the inner membrane of the mitochondrion -This enzyme makes ATP from ADP and inorganic phosphate

What are the separate roles of the components of the electron transport chain including flavin mononucleotide, the Fe-S group, ubiquinone, and the cytochromes

First redox rxn: Electrons acquired from glucose by NAD+ during glycolysis + citric acid cycle are transferred from NADH to the first molecule of the electron transport chain --> flavoprotein [named because it has a prosthetic group called flavin mononucleotide] Second redox rxn: Flavoprotein returns to its oxidized form as it passes the electrons to an iron-sulfur protein (Fe-S) Third redox rxn: Fe-S passes electrons to a compound called ubiquinone [small hydrophobic molecule, only member of chain that is not a protein, "CoQ"]

Where does the citric acid cycle occur?

Matrix of mitochondria

What is fermentation?

-An extension of glycolysis that allows continuous generation of ATP by the substrate level phosphorylation of glycolysis -Occurs without oxygen or an electron transport chain

Proton-Motive force

-Certain members of the electron transport chain accept and release protons (H+) along with electrons -At certain steps of the chain, electron transfers cause H+ to be taken up and released into the surrounding solution -Proton-Motive force is the H+ gradient that results which drives the H+ back across the membrane through the H+ channels provided by ATP synthasese

How does the electron transport chain and its release of energy eventually lead to ATP synthesis?

-Chemiosmosis

When does most of the ATP produced by respiration actually result?

-From oxidative phosphorylation, when the NADH and FADH2 produced by the citric acid cycle and earlier steps relay the electrons extracted from food to the electron transport chain --> During this process, they supply the necessary energy for the phosphorylation of ADP to ATP

How does the enzyme Phosphofructokinase regulate cellular respiration?

-It is an allosteric enzyme with receptor sites for specific inhibitors and activators -It is inhibited by ATP and stimulated by AMP, which the cell drives from ADP -As ATP accumulates, inhibition of the enzyme slows down glycolysis ---> enzyme becomes active again when cellular work converts ATP to ADP faster than the ATP is being regenerated

What is the source of muscle pain after an exercise session?

-Lactate that accumulates

How is ATP synthesized in muscle cells during a strenuous workout?

-Lactic acid fermentation

GTP (guanosine triphosphate)

-Molecule similar to ATP in its structure and cellular function -Can be used to make an ATP molecule or directly power work in the cell

Does the electron transport chain make any ATP?

-No, it eases the fall of electrons from food to oxygen, simplifying what would be a large free-energy drop into a series of smaller steps that release energy little by little

Describe the oxidation-reduction that the components of the electron transport chain undergo as electrons are accepted and donated. Include in your answer the direction of electronegativity

-Primarily, during the electron transport that occurs throughout the chain, electron carriers alternate between reduced and oxidized states as they accept and donate electrons. Electronegativity increases moving down the chain -Reduction: When a component accepts electrons from its uphill neighbor [which is the less electronegative neighbor] -Oxidation: The component returns to its oxidized form as it passes its electron downhill [more electronegative neighbor]

How does ATP synthase work like an ion pump running in reverse?

-Rather than hydrolyzing ATP to pump protons against their gradient, under the conditions of cellular respiration, ATP synthase uses the energy of an existing ion gradient to power ATP synthesis -The power source for ATP synthase is a difference in the concentration of H+ on opposite sides of the inner mitochondrial membrane

What are all of the products of the citric acid cycle and how are they used?

-Recall that each glucose gives rise to two molecules of acetyl CoA so the following products are equivalent to what one acetyl CoA group would yield, but the total yield per glucose would be doubled: -3 [6] NAD+ are reduced to [6] NADH -Electrons are transferred to FAD, which accepts 2 electrons and 2 protons to become [2] FADH2 -When CoA is displaced by a phosphate group, which is transferred to GDP, GTP is formed through the substrate level phosphorylation -GTP is used to generate the one [two] ATP molecule that is produced during the citric acid cycle -Overall: 6 NADH, 2 FADH2, 2 ATP

Cytochromes

-Remaining electron carriers between ubiquinone and oxygen -Their prosthetic group --> Heme group [has an iron atom that accepts and donates electrons] -Last cytochrome of the chain, Cyt a3, passes its electrons to oxygen ---> Very electronegative

What step links glycolysis and the citric acid cycle?

-The conversion of pyruvate to acetyl coenzyme A (acetyl CoA) -Carried out by a multicomplex enzyme that catalyzes three rxns

How are the first two stages of cellular respiration linked to Oxidative phosphorylation [3rd Stage]

-The first two stages [glycolysis and citric acid cycle] only produce a total of 4 ATP per glucose molecule so the NADH and FADH2 account for most of the energy extracted from the glucose molecule ---> oxidative phosphorylation uses energy released by the electron transport chain as electrons are relayed from the carriers to the chain to power ATP synthesis

What determines whether yeast or bacteria will use the fermentation or oxidative phosphorylation pathways?

-The presence of an electron-transport chain

Chemiosmosis

-The process, in which energy stored in the form of a hydrogen ion gradient across a membrane is used to drive cellular work such as the synthesis of ATP

Why are NADH and FADH2 so important?

-They contain stored electrons that are used during the electron transport chain portion

Prosthetic groups

-Tightly bound to proteins that compose the electron transport chain, non protein components such as cofactors and coenzymes essential for the catalytic functions of certain enzymes

How does the inner mitochondrial membrane or the prokaryotic plasma membrane generate and maintain the H+ gradient that drives ATP synthesis by the ATP synthase protein complex?

-the electron transport chain establishes the H+ gradient -The chain is an energy converter that uses the exergonic flow of electrons from NADH and FADH2 to pump H+ across the membrane, from the mitochondrial matrix into the intermembrane space -H+ has a tendency to move back across the membrane, diffusing down its gradient [from intermembrane space back into mitochondrial matrix] ---> ATP synthases are the only sites that provide this route for the H+ to do so

What is the total number of ATP molecules extracted from a single molecule of glucose by cellular respiration? Indicate the number of ATP molecules from each step and how they were produced.

1. 2 ATP from glycolysis [substrate level phosphorylation] 2. 2 ATP from the citric acid cycle [substrate level phosphorylation] 3. 26 or 28 ATP [oxidative phosphorylation, Each NADH that transfers a pair of electrons from glucose to the electron transport chain contributes enough to the proton-motive force to generate a maximum of about 3 ATP] MAX per glucose: 30 or 32 ATP

How do alcohol and lactic acid fermentation differ?

Alcohol fermentation: Pyruvate is converted to ethanol in two steps [1. CO2 is released from the pyruvate --> acetaldehyde 2. acetaldehyde is reduced by NADH to ethanol --> regenerates NAD+ needed for glycolysis] Lactic acid fermentation: Pyruvate is reduced directly by NADH to form lactate as an end product, regenerating NAD+ with no release of CO2