Discussion Questions for Week 5: hwa pages 167-179



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Discussion Questions for Week 5: HWA Pages 167-179



  1. Define and briefly describe the major sets of reactions in aerobic catabolism.

Glycolisis: Set of reactions in the cytosol where one molecule of glucose (or glycogen) is converted to 2 pyruvic acids. 2 ATP are consumed and 4 are produced, 2 NAD are reduced to 2 NADH.

Krebs Cycle: The pyruvic acid from glycolisis enters a cycle with acetyl coenzyme A in the mitochondria where the pyruvic acid is oxidized. 4 NAD are reduced to NADH, 1 GTP molecule is produced (which eventually leads to 1 ATP) per molecule of pyruvic acid.

The ETC: Series (“steps”) of reactions consisting of 4 major protein complexes in the inner mitochondrial membrane that “pass” electrons from NADH and FADH to O2 (the final electron acceptor), oxidizing NADH and FADH to NAD and FAD.

Oxidative Phosphorylation: This is the actual reaction that occurs when energy released from passing electrons through the ETC is used to convert ADP to ATP. For each NADH molecule, there is a potential yield of 3 ATP.


  1. How are oxidative phrosphorylation and substrate level phosphoylation different?


Oxidative phosphorylation uses energy released from the ETC occurring in the mitochondria, while sybstrate level phosphorylation occurs immediately in the reaction of substrates of glycolysis and the Krebs cycle.


  1. HWA states that, in a very narrow sense, glycolysis and the Kreb’s cycle can proceed without O2. Why, then, is O2 necessary for aerobic catabolism?


O2 is necessary for the reduction of NADH and FADH2 in the electron transport chain. NADH and FADH2 carry electrons, but can’t serve as the final resting place for electrons because the cell would run out of its supply. O2 picks up these electrons and is reduced to water. O2 is the final electron acceptor.



  1. For each electron pair that originally comes from NADH and passes completely through the electron transport system, how many ATPs are produced?


Theoretically 3



  1. The production of lactic acid in anaerobic conditions can be both a benefit and a disadvantage. Explain why.


It’s a benefit because lactic acid has the potential for further energy yield when considering that lactic acid can be further oxidized. It may be advantageous to many animals if some of this lactic acid can be retained for future use. Furthermore, when pyruvic acid is converted to lactic acid NADH is oxidized. This helps create a redox balance. It is a disadvantage because, as HWA states, it is a metabolic cul-de-sac. The accumulation of lactic acid in high concentrations can be harmful, and so high concentrations must be broken down. Lactic acid is converted back to pyruvic acid, and in order to break it down to pyruvic acid, oxygen is required (Kreb’s Cycle) and ATP might be used as well (gluconeogenesis). So anaerobic catabolism cannot proceed for too long until oxygen is necessary to reverse its effects.



  1. Phosphagens can be used to produce ATP as well. How does this mechanism work?


There are two phosphagens we generally consider: creatine and arginine, although these are not the only known phosphagens. They provide high energy phosphate bonds, and can be used in the presence of an enzyme to convert ADP to ATP. Thus, they operate without oxygen use. This reaction occurs in the response of ATP concentrations, where a high ATP concentration shifts the reaction towards the production of the phosphagen and ADP, and vice versa for a low ATP concentration.



  1. It is common belief that lactic acid causes muscle fatigue. Based on your reading, do you believe this to be true?


No. It was once believed that lactic acid triggered fatigue, and then it was common thought that it was actually acidosis that triggers fatigue. However, many studies have analyzed the effects of pH on muscle cells and this does not seem to play a role in fatigue. Really, the accumulation of lactic acid seems to be a good indicator of fatigue, but certainly not a cause of it.



  1. What other factors are mentioned that are believed to cause muscle fatigue?


Changes in organ-level systems likely cause fatigue. The book gives the example of the drop in glucose levels after intense exercise. Hyperthermia is another example. Also, fatigue is usually caused by the changes in cell function during exercise. Specifically, the book mentions the flux of ions caused by muscle contractions. These fluxes change a cell’s ability to operate appropriately. For example, muscle contraction can result in an accumulation of Ca++ that can cause the muscle cell to lose its ability to develop force and maintain power during exercise.


  1. In glycolysis, how many CO2 molecules are formed for each glucose molecule oxidized?


Technically, CO2 molecules are formed in the Krebs cycle. 6 CO2 per glucose.


  1. The ETC pumps protons from the matrix to the core of the mitochondria. The protons become concentrated in the intermembrane space and tend to diffuse back into the matrix. What two types of proteins discussed may play a role in this back-diffusion?


ATP synthase is a coupling mechanism that produces ATP when a protons is pumped from the intermembrane into the matrix. This is the basis for oxidative phosphorylation. Some cells also have uncoupling protein 1. This uses back diffusing protons to create energy released as heat. How this works is still up for debate.


  1. What is the P/O ratio? When does a cell ever reach the theoretical maximum P/O ratio?


The P/O ratio describes the “number of ATP molecules formed per atom of oxygen reduced to water” during oxidative phosphorylation. Theoretically, when fully coupled the P/O ratio should be 3. However, it never reaches this number, likely because in the mitochondria may allow the slow return of some protons from the intermembrane space back into the core without the production of ATP. Still, the mechanisms are not entirely known.


  1. Compare the pros and cons of operating in a steady state versus a non-steady state.


Operating in a steady state means that you are using aerobic catabolism. Steady state mechanisms are not self-limiting and can go on indefinitely. The rate of acceleration of ATP production tends to be lower than unsteady states, and there is a lower peak rate of ATP production. Still, there is a much larger yield of ATP per episode than in an unsteady state. Unsteady states have a high rate of acceleration of ATP production and a high peak rate of ATP production. Phosphagens and use of oxygen stores in the body also have a fast rage of return to full potention of ATP production after each episode.



  1. Cheetahs and wolves, although both predators, have two different hunting methods. While wolves are known to move miles in pursuit of prey, cheetahs tend to attack with short, extremely fast sprints. Which muscle fibers would be most beneficial to each animal?


You would see both SO and FG muscle fibers. Often, they are intertwined. Still, it is true that the cheetah would likely have more developed FG muscle fibers and the wolf would have more developed SO fibers.


  1. Do a little research to find factors that can affect a person’s metabolism, then compare this to your reading. Say an individual wants to lose weight and is wondering if the best exercise is swimming or working out in gym. Based on your new knowledge, what would you suggest to this individual?


Working out in a gym would be the best option. According to the Merck Medical Handbook, when you workout, your body temperature rises and this is a key factor in raising metabolism. When you swim, however, you lose a lot of that heat through convection. In a gym, not only do you produce heat during exercise, but the temperature will remain elevated for a period of time after the workout as well. There is some debate over the rise in temperature during workout (is it really enough to increase metabolism?), but I thought this was pretty interesting none-the-less. Also, if the water is really cold, you might also increase your uncoupling processes to prevent the body temp from dropping. Also, if heat is the cause of fatigue (as it has been suggested), then swimming might keep your body temperature cooler and allow you to go longer. Another idea is that lifting weights is generally more anaerobic while swimming is more aerobic, which means an individual would be able to do work longer in the pool, thus increasing the amount of glucose that is broken down and the likelihood that the individual would eventually need to tap into their fat stores.


  1. Angie, a 15 yr old female, was admitted to the hospital because of recurrent episodes of pallor, jaundice, and an ulcer on her left leg. Diagnosis of hemolytic anemia had been made at the age of 3 months, and she had been transfused several times since the diagnosis. Physical examination showed jaundice, skeletal growth retardation, and enlargement of the spleen. An analysis of blood showed low Hb content, low RBC count, and elevated reticulocyte count. Morphologic analysis revealed a mixed population of RBCs containing some irregularly contracted cells with irregular surface projections. The life span of the RBCs was found to be severely shortened. Both total and indirect serum bilirubin levels were markedly elevated. Fecal urobilinogen excretion was increased. Biochemical analysis of RBC metabolites showed elevated levels of 2,3 bisphosphoglycerate (2,3 BPG) and reduced levels of ATP. A splenectomy was performed; the spleen showed congestion and the presence of hemosiderin granules. Following splenectomy, there was improvement in both the clinical and hematologic symptoms. An increase in hemoglobin concentration as well as in the number of RBCs and reticulocytes was observed. The biochemical composition of the RBCs did not change after splenectomy.

Please answer the following:



What is the problem with this patient?
What is the source of ATP in red blood cells?
What are Reticulocytes?
Why did her RBCs change shape?
What is bilirubin?
See Clinical Case Study


  1. How many ATP molecules are formed from one mole of glucose in glycolysis?


Through substrate level phosphoylation only you get 2 molecules of ATP per molecule of glucose, so one mole of glucose yields1.2044* 1024 molecules of ATP

Including oxidative phosphorylation, 8 molecules of ATP are formed per one molecule of glucose, so one mole of glucose yields 4.818* 1024 molecules of ATP


  1. In Kreb’s cycle, how many NADH molecules are formed from one glucose molecule?


8


  1. In Kreb’s cycle, how many ATPs are formed from one mole of glucose by substrate level phosphorylation?


2 ATP molecules are formed per molecule of glucose, so one mole of glucose yields 1.2044* 1024 molecules of ATP


  1. What acid is formed from the combination of acetyl CoA and oxaloacetic acid?


Citrate


  1. What is the name of the integral protein in the inner mitochondrial membrane responsible for conversion of ADP to ATP?


ATP Synthase


  1. When supplies of intracellular O2 become low, what is pyruvate converted to such that glycolysis can proceed?


Lactic acid


  1. From 10 moles of glucose, how many moles of ATP would be formed in glycolysis assuming O2 is plentiful in the cell?



If there are 8 molecules of ATP formed per molecule of glucose, 80 moles of ATP would be formed per 10 moles of glucose.


  1. From the intracellular oxidation of one mole of glucose, how many moles of CO2 would be formed in glycolysis? In Kreb’s Cycle?


None in glycolysis. 6 in Krebs.


  1. When one mole of glucose (180 g) is burned in a bomb calorimeter, 2816 kJ of heat is released. When one mole of glucose is completely oxidized in cellular metabolism, how much heat is released?


Eventually, 2816 kJ of heat will be released.
The book says that usually there’s only an energetic efficiency of 60-70%, so your students may argue that for one molecule of glucose, about 35% will be lost as heat. This is true on the short term, but eventually most all will be lost as heat – the amount of work done by muscle.


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