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1. Sit with Lab Group Find members of your group 2. Attendance with your phone Launch your Top Hat app on your smart phone or load the TopHat.com website, or text to the course’s phone number. 3. Get out your notebook Prepare to add additional notes to those you took on last night's reading assignment. A couple BioCore students want to celebrate “graduation” from BioCore. They wanted to hear if you might be interested in a semi-formal(?) banquet. Question 1: Are you interested in attending an End of the Year banquet for the completion of Biocore? A) I would Attend B) I would not Attend Question 2: I would be Willing to pay to attend this banquet for at most … A) $20 B) $15 C) $10 D) I answered that I am not interested Question 3: It would be best if the banquet took place on this date A) April 30th (The last thursday before Finals week) B) May 1st (Friday before finals) C) May 2nd (Saturday) Announcements • Today your assigned readings were these: Announcements • The learning goals from the textbook are: Glycolysis • Describe the overall result in terms of molecules produced in the breakdown of glucose by glycolysis • Compare the output of glycolysis in terms of ATP molecules and NADH molecules produced • • Citric Acid Cycle (Krebs) Explain how a circular pathway, such as the citric acid cycle, fundamentally differs from a linear pathway, such as glycolysis Describe how pyruvate, the product of glycolysis, is prepared for entry into the citric acid cycle Announcements • Outline of lecture notes provided once again for this topic in Course Pack Our goals are not achieved by only listening to a lecturer—you must actively do things in order to learn (Bio or Kung Fu) Last time we asked: Why do you breathe? What does this remind you of? The electron transport chain occurs in the inner membrane of the mitochondrion (in regions called “cristae”) ELECTRON TRANSPORT CHAIN H+ H+ H+ H+ H+ H+ + H+ H H+ H+ H+ + + + H+H H H H+ H+ H+ H+ H+ H+ Q H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ Cyt c Q NADH NAD+ H+ Complex I Inner membrane FADH2 FAD H+ Complex II O2 H+ H2O Complex III Complex IV 1. What is backwards? 2. How much ATP? 3. Poke hole? This is why we breathe rat poison cyanide & CO The electron transport chain occurs in the inner membrane of the mitochondrion (in regions called “cristae”) ELECTRON TRANSPORT CHAIN H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+H H+ H+ H+ + H+ H+ H+ H+ H+ H+ Q H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ Cyt c Q NADH Inner membrane FADH2 NAD+ FAD H+ H+ O2 H+ H2O Complex I Complex II Complex III Complex IV NADH-Q Reductase, FADH-Q Reductase, Cytochrome Reductase, Cytochrome Oxidase (NADH dehydrogenase, FADH dehydrogenase, Cytochrome complex, Cytochrome Oxidase) The electron transport chain occurs in the inner membrane of the mitochondrion (in regions called “cristae”) ELECTRON TRANSPORT CHAIN H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+H H+ H+ H+ + H+ H+ H+ H+ H+ H+ Q H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ Cyt c Q NADH Inner membrane FADH2 NAD+ FAD H+ H+ O2 H+ H2O Complex I Complex II Complex III Complex IV NADH-Q Reductase, FADH-Q Reductase, Cytochrome Reductase, Cytochrome Oxidase Cellular respiration If oxygen (aerobic) is present GLYCOLYSIS Glucose KREBS CYCLE ELECTRON TRANSPORT AND OXIDATIVE PHOSPHORYLATION Pyruvate If oxygen is NOT present (anaerobic) FERMENTATION 0.2 µm Mitochondria 0.2 µm Intermembrane space Outer membrane Free ribosomes Inner membrane Cristae ? 0.1 µm Electron transport chain SUMMARY OF CELLULAR RESPIRATION Electrons 2 NADH Glucose 2 NADH 2 Pyruvate 2 ATP Cytoplasm 2 Acetyl CoA 2 CO2 Oxidative phosphorylation H+ + + + + H H H HH + H+ + + H H+ H+ H H+ H+ H+ NADH 6 2 FADH2 KREBS CYCLE O2 4 CO2 2 ATP Mitochondrion So are the H+s really trapped? H 2O 26 ADP 25 ATP Maximum yield of ATP per molecule of glucose: 29 SUMMARY OF GLUCOSE OXIDATION 2 NADH Glucose 2 NADH 2 Pyruvate 2 ATP Cytoplasm 2 Acetyl CoA 2 CO2 Mitochondrion 6 NADH 2 FADH2 KREBS CYCLE 2 ATP 4 CO2 Where do we go next? SUMMARY OF GLUCOSE OXIDATION 2 NADH Glucose 2 Pyruvate 2 ATP Cytoplasm Mitochondrion Pyruvate Dehydrogenase Multienzyme Complex If you have O2, enter the Matrix SUMMARY OF GLUCOSE OXIDATION 2 NADH Glucose 2 Pyruvate 2 ATP Cytoplasm Mitochondrion Where do we go next? SUMMARY OF GLUCOSE OXIDATION 2 NADH Glucose 2 NADH 2 Acetyl CoA 2 Pyruvate 2 CO2 2 ATP Cytoplasm Mitochondrion SUMMARY OF GLUCOSE OXIDATION 2 NADH Glucose 2 NADH 2 Acetyl CoA 2 Pyruvate 6 NADH 2 FADH2 KREBS CYCLE 2 CO2 2 ATP Cytoplasm 2 ATP Mitochondrion 4 CO2 The two red carbons enter the cycle via acetyl CoA Acetyl CoA Citrate All 8 reactions of the citric acid cycle occur in the mitochondrial matrix, outside the cristae Isocitrate In each turn of the cycle, the two blue carbons are converted to CO2 α-Ketoglutarate Oxaloacetate The CITRIC ACID CYCLE runs twice for each glucose precursor In the next cycle this red carbon becomes a blue carbon Succinyl CoA Malate Each reaction is catalyzed by a different enzyme Fumarate Succinate What about this? Actually… Electrons carried via NADH Glycolysis Pyruvate Glucose Cytosol ATP Substrate-level phosphorylation Electrons carried via NADH and FADH2 Electrons carried via NADH Citric acid cycle Glycolysis Pyruvate Glucose Mitochondrion Cytosol ATP ATP Substrate-level phosphorylation Substrate-level phosphorylation Electrons carried via NADH and FADH2 Electrons carried via NADH Citric acid cycle Glycolysis Pyruvate Glucose Oxidative phosphorylation: electron transport and chemiosmosis Mitochondrion Cytosol ATP ATP ATP Substrate-level phosphorylation Substrate-level phosphorylation Oxidative phosphorylation All 10 reactions of glycolysis occur in cytosol GLYCOLYSIS What goes in: ATP ATP 1 Glucose What comes out: 2 Glucose6-phosphate ADP 3 Fructose6-phosphate 4 Fructose1,6-bisphosphate ADP Glycolysis begins with an energyinvestment phase of 2 ATP 5 PIP • Think of the beginning of “Glyco-lysis” as eating a pizza Think Glucose = Pizza The common ‘hexo-pyranose’ form of Pizza Meet PIP (Phosphorylate-Isomerize-Phosphorylate) • Is that really the best way to hold on to your pizza? Aldolase = Fructose 1-6 Bisphosphate -> DHAP (ick) and G-3-P (tasty!) Isomerase -> DHAP (ick) G-3-P (tasty!) Isomerase -> G-3-P (tasty!) G-3-P (tasty!) GLYCOLYSIS Energy-investment phase What goes in: ATP ATP P I 1 2 Glucose6-phosphate Glucose What comes out: P 3 Fructose6-phosphate ADP Hexokinase (capture) 4 Fructose1,6-bisphosphate ADP phosphoglucoisomerase PFK* ?????? [ATP] high 5 PFK is highly regulated ATP at active site ATP at regulatory site Fructose- 1,6bisphosphate at active site GLYCOLYSIS Energy-investment phase aldolase What goes in: ATP P I 1 P 2 Glucose6-phosphate Glucose What comes out: DHAP ATP 3 Fructose6-phosphate ADP hexokinase 4 stimulates isomerase Fructose1,6-bisphosphate ADP phosphoglucoisomerase 5 PFK* G-3-P G-3-P inhibits Glyceraldehyde-3-phosphate (G3P)-dehydrogenase [ATP] high [ADP] [AMP] Phosphoglycero(PG)-kinase Glyceraldehyde-3-phosphate(G3P)-dehydrogenase PIP All 10 reactions of glycolysis occur in cytosol GLYCOLYSIS What goes in: ATP ATP 1 Glucose What comes out: 2 Glucose6-phosphate ADP 3 Fructose6-phosphate 4 5 Fructose1,6-bisphosphate ADP G-3-P G-3-P Glyceraldehyde-3-phosphate(G3P)-dehydrogenase Glycolysis begins with an energyinvestment phase of 2 ATP Energy payoff phase Phosphoglycero(PG)-kinase The “2” indicates that glucose has been split into two 3-carbon sugars 2 NAD+ 2 ADP 2 6 2 G-3-P 2 2 7 1,3-BisPGA 8 2 9 2 ADP 2 10 Pyruvate 3-PGA pyruvate kinase 2 NADH 2 ATP 2 ATP G-3-P-dehydrogenase During the energy payoff phase, 4 ATP are produced for a net gain of 2 ATP