Mod+11+Reading+Guide

__**Mod 11 Summary**__: Module 11, metabolism and energy production, describes the citric acid cycle, electron transport chain, and process of ATP production that fuels activity in our cells.

__**23.1 = The Citric Acid Cycle**__ Summary: The **citric acid cycle** (or Krebs cycle) is a series of chemical reactions that degrades acetyl CoA to yield carbon dioxide and energy that makes NADH and FADH2. This citric acid cycle works with carbohydrates, lipids and proteins. The citric acid cycle includes 8 reactions, part 1 makes citrate, and part 2 makes oxaloacetate that can bond with another acetyl CoA and begin the cycle again. 1 rotation through the citric acid cycle causes four oxidation reacations to provide H+ and electrons with can be used to make FADH2 and NADH. **Decarboxylation** is a reaction that removes a CO2 molecule from a carboxylate group COO-. The steps of the citric acid cycle are [part 1] 1-formation of citrate, 2-isomerization to isocitrate, 3-first oxidative decarboxylation (OH becomes C=O, CO2 is removed, and NADH is produced), 4-second oxidative decarboxylation (CO2 is removed and NADH is produced), [part 2] 5-hydrolysis of succinyl Coa (produces ATP from GTP), 6-dehydrogenation of succinate (FAD becomes FADH2 when C=C forms), 7-hydration (water saturates C=C bond), 8-dehydogenation forms oxaloacetate (OH is oxidized and NADH is produced). In one turn of the citric acid cycle, the reactants, acetyl-S-CoA, 3NAD+, FAD, GDP, P, and 2H2O form the products, 2 CO2, 3 NADH, 3 H+, FADH2, HS-CoA, and GTP. The citric acid cycle is regulated by enzymes to be activated by high levels of NAD+ and ADP and inhibited by high levels of NADH and ATP.

Struggling Topic 1: How does NADH form ATP from ADP? Is it an enzyme that fits the structure of ADP and has an active site for a Phosphate group to bind with the ADP?

Struggling Topic 2: The citric acid cycle happens in the mitochondria of cells. Does this mean it does not occur for prokaryotes? Is it incorrect for me to teach my students that all organisms do cellular respiration? Can I include the glycolysis that prokaryotes do as a primitive form of cellular respiration?

__**23.2 Electron Carriers**__ Summary: Oxidative phosphorylation produces most of the ATP energy for the cell when oxygen is available for the mitochondria. The **electron transport chain** is the chemical reaction where hydrogen ions and electrons from NADH and FADH2 are passed to electron acceptors in order to form H2O and release energy to synthesize ATP. Electron acceptors are known as **electron carriers**. Each electron carrier contains a group or ion that is reduced when electrons are accepted (AH2) and oxidized when electrons are removed (A). The four main electron carriers in the electron transport system are: **FMN (flavin mononucleotide)**, **Fe-S**, **Coenzyme Q (CoQ)**, and **Cytochromes (cyt)**. FMN is a coenzyme that contains a flavin ring system also found in FAD. Fe-S clusters have groups of iron-sulfur proteins that allow iron to be reduced to Fe2+ or oxidized to Fe3+ as electrons are gained and lost. CoQ is derived from quinone (six carbon cyclic compound with two keto groups that can accept electrons and H+). Cytochromes include an iron ion in a heme group (Fe+3 + 1e- --> Fe+2).

Struggling Topic 1: What is a flavin group? It wasn't one of the original functional groups we studied earlier this year. When I googled it, it looked like it was a compound with 3 6-atom cyclical bonds including nitrogen atoms and ketones.

Struggling Topic 2: Are the cytochromes that include a heme group related to the hemoglobin in blood? I sounds like the same heme group is oxidized and reduced in both.

__**23.3 Electron Transport**__ Summary: Electron transport happens along the folded inner membrane of the mitochondrion. Four different protein complexes exist in these membranes, and electron carriers, CoQ and cytochrome c function as mobile carriers that shuttle electrons between these complexes. **Complex 1, NADH Dehydrogenase**, includes proteins that oxidize NADH to NAD+ by transferring protons to FMN. The NAD+ then returns to the citirc acid cycle to oxidize more substrates. At the end of complex 1, CoQ is reduced and accepts 2 H atoms. The total reaction in complex 1 looks like FADH2 + Q --> QH2 + NAD+. **Complex 2, Succinate Dehydrogenase**, is used when FADH2 is generated from the citric acid cycle. FADH2 is oxidized while CoQ is reduced to QH2. Complex 2 has electrons that are at lower energy levels than Complex 1, so these electrons enter electron transport at a lower energy level. FADH2 + Q --> FAD + QH2. **Complex 3, CoQ-Cytochrome c Reductase**, QH2 transfer the electrons it has collected from NADH and FADH2 to an Fe-S cluster and then to cytochrome b and then to cytochrome c. Cytochrome c then moves electrons from complex 3 to complex 4. QH2 + 2 cyt b (Fe 3+) --> Q + 2 cyt b (Fe 2+) + 2 H+. **Complex 4, cytochrome c Oxidase**, is the final step of electron transport that transfers electrons from cytochrome c to cytochrome a to cytochrome a3 and finally to O2 to yield H2O. 4 H+ + 4 e- + O2 --> 2H2O.

Struggling Topic 1: It sounds like Complex 1 or 2 must come before complex 3 which must come before complex 4. Is this the case? It sounds like complex 3 and 4 are really a two step complex that go together while complexes 1 and 2 both serve to oxidize CoQ so that complexes 3 and 4 can function.

Struggling Topic 2: Is it legitimate to write the complex 4 reaction as 4 H+ + 4 e- + O2 --> 2 H2O? I don't particularly like the 1/2 O2 that the book uses in the reaction. Is there a particular reason why the book uses 1/2 O2 here?

__**23.4 = Oxidative Phosphorylation and ATP - quiz questions on this one too**__ Summary: **Oxidative phosphoylation** is the process that produces ATP as substrates are oxidized through the electron transport chain. The **chemiosmotic model** links the energy from electron transport to a proton gradient that drives the synthesis of ATP. Each of the complexes act as 1 way roads, **proton pumps**, for protons into the intermembrane space of the mitochondrion that pushes protons out of the matrix and into the intermembrane space. This lowers the pH of the intermembrane space and increases the positive charge of the intermembrane space to make the protons want to leave the space, but to do so, they must pass through **ATP synthase** that uses this energy flow to combine a P group with ADP and form ATP. **ATP Synthase** is made of two protein complexes. One protein complex, F0 is the channel through which protons return to the matrix of the mitochondrion. The other protein complex, F1 contains a center subunit with three surrounding subunits and three active sites with different shapes: L for loose, T for tight, and O for open. As the flow of protons through F0 continues, F1 turns so that the L, T, and O active sites rotate. Thus ATP is synthesized by first binding ADP and P to an L site. Then energy from the F1 center converts all the sites so that L becomes T, O becomes L, and T becomes O. This causes ADP and P that are now in a T site to spontaneously form ATP. Lastly, another turn from F1 changes the active sites again so that ATP's site becomes an O site which has minimal attraction to ATP, so ATP is released. When the site is open it may again accept ADP and P to begin again. The **oxidation of NADH2 yields 3 ATP** while the **oxidation of FADH2 yields 2 ATP** because electrons from NADH2 are oxidized at a higher energy level than electrons from FADH2. Oxidative phosphorylation is regulated by the availability of ADP, P, oxygen and NADH.

Struggling Topic 1: Is the inner membrane of the mitochondrion different from most other cell membranes? It would seem practical for ATP to be able to diffuse through most cell membranes, but can it? If ATP cannot diffuse through membranes of cells, then how is it transported?

Struggling Topic 2: Is it correct that the binding of the ADP and P to the L site on the F1 complex does not require energy, but the turning of the F1 complex that changes the L site to a T site does require energy? This is where the idea that the release of ATP requires energy from the electron transport chain, right?

__**23.5 ATP Energy from Glucose**__ Summary: ATP is produced in many different ways including glycolysis, oxidating pyruvate, the citric acid cycle, and the electron transport chain. NADH cannot cross the mitochondrial membrane, so uses FAD where the H+ and electrons are transferred into the mitochondrion. This causes NADH from the cytoplasm to create only 2 ATP molecules because it transfers H+ and electrons to FAD before entering the mitochondrion. In glycolysis, 6 ATP are produced (2 from direct phosphorylation and 4 from NADH add up to **6 ATP from glycolysis**). During the oxidation of pryuvate, 2 pyruvate molecules were generated from 1 glucose, and this produces **6 ATP from the oxidation of pyruvate**. In the citric acid cycle, 1 glucose molecule produces 2 CO2, 3 NADH, 1 FADH, and 1 ATP by direct phosphorylation. The 3 NADH each produce 3 ATP for a total of 9 ATP, and the 1 FADH produces 2 ATP. Thus each turn of the citric acid cycle produces 12 ATP, and each glucose molecule produces two acetyl CoAs under aerobic conditions, so the citric acid cycle turns twice per glucose molecule and yields **24 ATP in the citric acid cycle for each glucose**. All of this together produces a **total of 36 ATP per glucose molecule.**

Struggling Topic 1: Approximately how much ATP do we use each day? How many glucose molecules must be broken down daily to supply this amount of ATP production?

Struggling Topic 2: If we were perpetually in an anaerobic environment, would we die because of an ATP shortage, or would we die from some other cause?

__**Critique**__ __Good examples__ 23.4 - The steps of ATP Synthase and pictures that accompanied them made it easy to understand where the energy in ATP synthesis is needed and how it is obtained.

__Needed more examples__ 23.5 - the chart that added the ATP production and use for the varied pathways of glucose would have been too confusing alone. The descriptions in the paragraphs that explained it were very helpful.

__Place in the chapter (relative to others)__ 23.5 - it is good that this summary of ATP production come after we have covered glycolysis, the oxidation of pyruvate, and the citric acid cycle, otherwise the summary would seem to bring up more questions that it answers.