BCH 380 1st Edition Exam 3 Study Guide Lectures 22 29 Chapters 19 21 24 28 Lecture 22 March 18 Chapter 19 The Citric Acid Cycle Know the steps in the CAC i e substrates products and reaction types Know the enzymes and the reactions they are catalyzing Know points in cycle where electrons are harvested and where energy is gained Citric Acid Cycle CAC Regulatory Points Step Reaction Molecules Enzyme Extra Notes Energy gained and CO2 lost 1 Condensation Acetyl CoA Oxaloacetate to Citrate Citrate Synthase Lose CoA 2 Dehydration hydration Isomerization Citrate to Isocitrate Acconitase 3 1st Oxidative Decarboxylation Event capture electrons Isocitrate to Isocitrate Dehydrogenase NAD to NADH 4 2nd Oxidative Decarboxylation Event capture electrons Alpha ketogluturate to Succinyl CoA Alpha ketogluturate dehydrogenase NAD to NADH 5 Phosphorylation Succinyl CoA to Succinate Succinyl CoA Synthetase GDP to GTP alpha ketogluturate Lose CO2 Lose CO2 Or ADP to ATP Lose CoA Gain Pi 6 Dehydrogenation Oxidation Harvest electrons Succinate to Fumerate Succinate Dehydrogenase 7 Hydration Fumerate to Malate Fumerase 8 Malate to oxaloacetate will add back to acetyl CoA to Mitochondrial m malate dehydrogenase FAD to FADH2 NAD to NADH start cycle again Net Gain 3NADH 1FADH2 1ATP or GTP Net Loss 2CO2 at the regulatory points Series of oxidation reduction reactions in the mitochondria take 1 acetyl CoA to 2 CO2 Primary Function to harvest high energy electrons for proton pumping in the electron transport chain these used to drive ATP formation from oxidative phosphorylation Want to maximize the capture of increased transfer potential electrons while regenerating oxaloacetate Considered aerobic because NAD FAD can only regenerate via electron transfer chain 2 Basic Parts 1 Oxidize Acetyl CoA that was made from pyruvate to CO2 and capture the electrons 2 Regenerate the starting product oxaloacetate to continue the cycle Regulation of CAC where and how Pyruvate to acetyl CoA is important but acetyl coA can be derived from fatty acid metabolism so needs more control 2 Primary Control Points 1 Isocitrate Dehydrogenase Lecture 23 March 23 Chapter 20 Electron Transport Chain What are the steps in the ETC with regard to e flow for NADH and FADH2 What are the names of membrane proteins proton pumps mobile e carriers and roles in eflow List generalities about the chemical structure of e carriers within proton pumps and mobile carriers Movement of Electrons and Protons Through the ETC o Complex I proton pump Uses Complex II to carry electrons through complex II to complex III Accepts NADH NADH to NAD electrons Pumps out 4 H o Complex II Intermediate electron carrier protein Intermediate Protein Complex II Accepts e from FADH2 and gives them to Q for transfer to Complex III We lose the 4H pumped in Complex I o Q mobile e carrier 2e carrier from Complex II to Complex III o Complex III proton pump Uses cytochrome C to pump electrons from Complex III to Complex IV Pumps from e from either NADH or FADH2 Pumps out 4 H o Cytochrome C moves electrons one at a time instead of 2 at a time as with Q from Complex III to Complex IV o Complex IV proton pump Pumps 2 H Reduces O2 to form H2O O2 is the final electron acceptor Needs 4e to reduce oxygen to water at this terminal site of the ETC Overall yield of pumped protons from NADH and FADH2 o 6 FADH2 o 10 NADH What are the Parts of the ETC o Each component of the mitochondrial ETC has prosthetic groups that are involved in shuttling the e o Key among these are flavins Fe complexes of Fe S and heme as well as copper complexes o All are used to stabilize e on their way to reduce oxygen and the energy of the e movement is used to pump protons o Sets up concentration gradient for ATP Synthase Lecture 24 March 25 Chapter 21 Proton Motive Force Oxidative Phosphorylation Define chemiosmosis and how it relates to ATP Synthase The proposal that e transport and ATP synthesis are coupled by a proton gradient across the mitochondrial membrane Structure and function of ATP synthase important protein parts F0 and F1 subunits ATP Synthase has two major domains 1 Fo subunit a proton channel domain composed of a hydrophobic subunit that spans the mitochondrial membrane and through which the protons flow down their concentration gradient back into the matrix These are called half channels This subunit is also known as the C Ring 2 F1 subunit The place where ATP is synthesized Has 5 types of polypeptide chains o a3b3 alternating hexamer arranged around a g subunit and an e subunit that makes up the stalk that extends down into the a3b3 hexamer o Also a delta subunit that is mostly structural and does not have a role in ATP synthesis What are the rotor stator protein parts and protein conformational changes L T O o Synthesis of ATP occurs at the Beta subunits As the asymmetric gamma stalk rotates the conformation of the beta subunit changes which induces a conformational change of the beta subunit between the L T and O conformations o The O L conformation open to loose binds ADP and Pi L T loose to tight forms ATP and the T O releases ATP and is open for binding more ADP and Pi Describe the mechanism for proton induced C ring movement through half channels o An aspartic acid in the dimeric membrane spanning alpha helices can be protonated which induces a conformational change causing rotational movement o After a full turn the proton from the intermembrane space is dumped back into the matrix o Number of ATP made is dependent on number of C ring half channels which differs between species o We have 10 half channels What is the overall ATP yield from NADH and FADH2 overall from glucose acetyl CoA fatty acids 1 NADH pumps 10 protons A C Ring with 10 half channels would make 3 ATP 10 protons Thus the old but wrong number of 3 ATP per NADH that is in many books Making ATP takes phosphate and this requires use of 1 proton ATP Thus the best approximation for of ATP NADH is 2 5 For FADH2 the best is 1 5 In liver where FADH2 made in first stage 5 ATP not 3 ATPs are made gives total of 32ATP at the end What happens to cytosolic NADH Liver versus muscle 32 ATP for liver and Heart because of Malate Shuttle used to transport e And give to NADH in mitochondria Lecture 25 April 6 Chapter 24 Glycogen Degradation Review glycogen structure and linkages Glycogen is a polysaccharide consisting of a 1 4 linked glucose with a 1 6branched glucose every 10 residues Glycogen is a readily mobilized form of glucose that is