TCA & ETC Published on August 30, 2020 by ehudspeth TCA & ETC Following extreme trauma, the body would use which TCA intermediate to replace lost heme? Oxaloacetate Citrate Alpha-ketoglutarate Succinyl CoA Succinate Wernicke-Korsakoff syndrome is a neurological disorder characterized by mental confusion, amnesia (a permanent gap in memory), and impaired short-term memory. Which of the following enzymes would have reduced function due to this disorder? Pyruvate carboxylase Lactate Dehydrogenase Pyruvate Dehydrogenase Malonate Dehydrogenase Methylmalonyl-CoA mutase Alcoholics typically have markedly diminished function of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase due to decreased dietary absorption of: Thiamine S-adenosyl methionine Succinate Riboflavin Biotin A patient comes to your office with kidney and liver failure. You suspect that methylmalonic acidemia might be their diagnosis which would mean that they are likely deficient in which of the following enzymes? Vitamin B1 Vitamin B2 Vitamin B3 Vitamin B5 Vitamin B12 Which of the following is a anapleurotic reaction that occurs in the TCA cycle? Aspartate → Oxaloacetate Succinyl CoA → Heme Citrate → Fatty Acids Glutamate → citrate Lysine → Succinate Which of the following is true regarding succinate dehydrogenase? It requires Vitamin B1 (Thiamine) It oxidizes NADH → NAD+ It is involved in both the ETC and TCA cycle It requires Vitamin B7 (Biotin) It produces GTP in its reaction of succinate → fumarate What unique property of non-alpha tocopherols makes them an essential part of a good diet? Its higher favorability for oxyradicals Its ability to inhibit COX, 5LOX and RNS Its higher concentration in tissues than alphaT Collaborative function with ascorbate The ability to neutralize toxic NAPQI When there is a bloodborne infection, cells of the immune system produce vast amounts of nitric oxide to destroy the pathogen. This dilates blood vessels and can cause blood pressure to plummet – a condition called septic shock. Which of the following is an additional reason for why an accumulation of NO could be dangerous? Excess amounts of nitric oxide can react with superoxide radicals forming peroxynitrite (ONOO-) Excess amounts of nitric oxide can react with free oxygen radicals forming peroxynitrite (ONOO-) Peroxynitrites (ONOO-) can break down into Nitrogen dioxide radicals (•NO2) and hydroxyl radicals (•OH) A & C B & C Damage to the ETC by means of cyanide poisoning would lead to leakage of electrons through which channels? Complex I Complex II Complex III Complex IV Complex I and III Ischemic strokes occur when the arteries to your brain become narrowed or blocked, causing severely reduced blood flow. Which of the following best describes how a patient’s ETC would be affected if they were experiencing a stroke? The lack of blood flow would directly inhibit the function of Complex I and cause a subsequent release of reactive oxygen species from Complex I The lack of blood flow would directly inhibit the function of Complex III and cause a subsequent release of reactive oxygen species from Complex I and III The lack of blood flow would directly inhibit the function of Complex IV and a subsequent release of reactive oxygen species from Complex I and III The lack of blood flow would directly inhibit the function of Complex IV and cause a subsequent release of reactive oxygen species from Complex I and II The lack of blood flow would directly inhibit the function of Complex II and cause a subsequent release of reactive oxygen species from Complex I and II As a third year medical student, your resident shows you a patient file showing a confirmed diagnosis of chronic granulomatous disease, which is caused by an enzyme mutation in NOX-2. Where is this enzyme located that it would lead to symptoms associated with this condition? The inner mitochondrial membrane The outer mitochondrial membrane Intracellular phagosome membrane Extracellular membrane This is cause by a free enzyme in the cytosol You are on rotations in an underserved primary care clinic when you come across a patient who can’t stop talking about the importance of antioxidants. They tell you that they researched it on “the Google machine” and that they know all there is to know about antioxidants. When asked, the patient revealed that they’ve been taking Vitamin E for the past 5 years in order to rid their body of reactant radicals. What should you tell them? Keep doing what they’re doing, Vitamin E is a great source of alpha-tocopherol which is important in ridding the body of radicals They are mistaken and should actually be taking Vitamin D to get the effect they’re wanting Keep doing what they’re doing, Vitamin E is a great source of gamma-tocopherol which is important in ridding the body of radicals While Vitamin E is a great source of gamma-tocopherol, it doesn’t include the other “non-gamma” tocopherols which are also important in ridding the body of free radicals While Vitamin E is a great source of alpha-tocopherol, it doesn’t include the other “non-alpha” tocopherols which are also important in ridding the body of free radicals You are doing clinical rotations in the Emergency Department when a patient comes in who had overdosed on Aspirin. Their symptoms include hyperventilation, vomiting, dehydration, double vision, fever, and feeling faint. A resident asks you to explain the reasoning for why this patient is exhibiting a fever. What are you going to tell them? High dose aspirin works as a chemical uncoupler, producing excess heat with the associated energy release The fever due to the body’s immunological response to the overabundance of Aspirin Aspirin activates UCP1 causing thermogenesis and dissipation of heat from brown adipose stores The body creates a fever in order to provide a more suitable environment for the enzymes responsible for metabolizing the Aspirin The patient probably has an associated infection. Hemochromatosis is a disease in which too much iron builds up in your body. The fenton reaction explains why this buildup of iron can be so dangerous. Which of the following best describes the Fenton reaction? Fe2+ can react with hydrogen peroxide, producing hydroxyl radicals Fe2+ can react with other metals such as Cu+ to produce hydroxide Fe2+ can react with free oxygen, producing superoxide radicals Fe2+ can react with hydrogen peroxide, producing superoxide radicals Fe2+ can react with free oxygen, producing hydroxide Which of the following is considered to be the most dangerous reactive oxygen species (ROS)? Superoxide radical Hydrogen peroxide Hydroxyl radical Hydroxide ion Oxygen The legend of vampires is believed to have stemmed from individuals who had the disease porphyria which can often include symptoms such as sensitivity to sunlight which can be treated with exogenous blood ingestion. Deficiency in which TCA cycle intermediate can lead to porphyria? Oxaloacetate ɑ-ketoglutarate Citrate Fumarate Succinyl-CoA Veronica suffers from anorexia nervosa causing her to have low vitamin B1 levels. Which of the following coenzymes related to the pyruvate dehydrogenase complex would she have trouble synthesizing? TPP Lipoate FAD NAD+ CoA Isocitrate dehydrogenase is the TCA enzyme responsible for the oxidative decarboxylation of Isocitrate to α-ketoglutarate. In IDH mutations, mutant isocitrate dehydrogenase additionally reduces α-ketoglutarate to D-2-hydroxyglutarate (2-DHG). How does this mutant TCA oncometabolite compromise cellular integrity that potentially leads to cancer? 2-DHG through feedback inhibition ceases the enzymatic activity of Isocitrate dehydrogenase. 2-DHG competitively inhibits α-ketoglutarate dependent dioxygenases. 2-DHG allosterically activates succinate dehydrogenase to produce metastatic levels of α-ketoglutarate. 2-DHG irreversibly activates α-ketoglutarate dependent dioxygenases that generate onco-enzymatic proteins that promote unregulated cell proliferation. Fumaric aciduria is a rare autosomal recessive metabolic disorder characterized by a deficiency of the enzyme fumarate hydratase (fumarase), which causes a deficiency of malate. What effect would this have on the production of ATP?Fumaric aciduria is a rare autosomal recessive metabolic disorder characterized by a deficiency of the enzyme fumarate hydratase (fumarase), which causes a deficiency of malate. What effect would this have on the production of ATP? This would cause a build up of oxaloacetate in the mitochondria This would cause glycolysis to not be able to occur in the mitochondria This would cause glycolysis to not be able to occur in the cytoplasm This would cause the electron transport chain to collapse This would cause oxaloacetate to be converted to malate at a slower rate Which of the following enzymes reduce a vitamin B2 derivative through their enzymatic activity in the TCA cycle? Malate dehydrogenase Fumarase Isocitrate dehydrogenase Succinate dehydrogenase Aconitase Which of the following below contains the three enzymes that produce NADH during the TCA Cycle? Isocitrate dehydrogenase, ɑ-ketoglutarate dehydrogenase, Succinyl-CoA synthase Succinate dehydrogenase, Isocitrate dehydrogenase, Succinyl-CoA synthase Malate dehydrogenase, Isocitrate dehydrogenase, Succinate dehydrogenase Malate dehydrogenase, Isocitrate dehydrogenase, ɑ-ketoglutarate dehydrogenase Malate dehydrogenase, ɑ-ketoglutarate dehydrogenase, succinate Dehydrogenase Molly’s pediatrician told her that she could give acetaminophen to her 6 month old for fevers. She didn’t have any acetaminophen so she gave her baby baby aspirin which she thought would be okay because it had the word baby in the name. Which of the following explains what would happen? Her baby’s fever would decrease because aspirin and acetaminophen are interchangeable and you can use them at alternating times Her baby’s fever would decrease because the aspirin would work to block the COX1 and COX2 pathways Her baby’s fever would decrease because the aspirin would work to block the 5-LOX pathway Her baby’s fever would spike because aspirin would uncouple the ETC causing heat instead of ATP to be formed. Her baby would die because aspirin would decrease the infant’s ability to clot so they would bleed out. In the early 1960’s the benefits of Vitamin E were discovered and doctors started prescribing it as a pill to virtually everyone. Which of the following explains why this was not effective in preventing many of the diseases that natural vitamin E had been seen to prevent? Most of the patients had scurvy so the were unable to turn the free radicals into the aqueous form and therefore unable to rid the body of them. Vitamin E supplements were only one form of tocopherols and when they were taking the pills, they were depleting the other forms thus unable to oxidize in other ways. Vitamin E must be taken as a part of a multivitamin or else it depletes the other vitamins and causes more harm than good Even if they had the increased Vitamin E, they would still have the same amount of Glutathione so they would be unable to oxidize the radicals. In larger doses, vitamin E actually causes more free radicals to form. In most infections (especially bacterial), neutrophils are characterized as the first responders as they often the first leukocyte to be elevated and attempt to resolve the infection. Neutrophils are also characterized as phagocytes which means they ingest their targets and then fuse them with lysosome to degrade them. Phagocytes also implement reactive oxygen species is order to damage and destroy their ingested targets. Which NADPH oxidase (NOX) enzyme is found in these types of cells? NOX 1 NOX 2 NOX 3 NOX 4 NOX 5 Nitric oxide is created in endothelial cells of blood vessels when acetylcholine binds to its G protein coupled receptor. What enzyme will the G alpha subunit activate after acetylcholine has bound? Adenylyl Cyclase Guanylyl Cyclase Phospholipase C Phosphodiesterase Nitric Oxide Synthase Kevin wanted to look cool when he went to his first rave festival, so he took amphetamines that he got from the sketchy looking man in the bathroom line. Unfortunately they were laced with MPP+ and Kevin woke up confused in the hospital with tremors in his hand, stiff muscles, and feeling very fatigued. Which of the following explains his symptoms? The MPP+ caused complex I of ETC to not work The MPP+ caused complex II of ETC to not work The MPP+ caused complex III of ETC to not work The MPP+ caused cytochrome C of ETC to not work The MPP+ caused Coenzyme Q of ETC to not work People suffering from Crohn Disease are frequently deficient in many vitamins including Selenium due to their inability to absorb vitamins despite their consumption. Which of the following would be affected by a selenium deficiency? Glutathione Superoxide dismutase I Superoxide dismutase II Catalase Glutathione-Peroxidase People with hemolytic anemia have problems reducing glutathione. Hemolytic anemia results in the rupture of red blood cells. Which of the following would NOT be a problem for people with this disease? They are not able to regenerate NADPH They get a buildup of H2O2 in their cells They get a buildup of hydroxyl radicals They get a buildup of NADPH They have a reduced number of RBCs In the very young and the elderly, it is common to be deficient in the various B vitamins. If one of these individuals is deficient in both cobalamin and pyroxidine, they will get a toxic buildup of which product? Methyl Malonyl CoA Uric Acid Hydrogen Peroxide Glutathione Homocysteine Time is Up!