University:
Boston University
Course:
CAS BI 525 | Biology of Neurodegenerative Diseases
Academic year:

2024
Views:

465

Pages:

4
Author:

Dimaltah3kw

Phosphorylation The Respiratory Chain and ATP Synthase Produce ATP by a Chemiosmotic Mechanism Animation of ATP Synthase OUTLINE: Pyruvate pyruvate dehydrogenase Krebs’ Cycle How did he figure it out? Overview 8 Steps Energetics Regulation Summary • • • Every F0 turn uses 8-17 H+ Every turn gets 3 ATP Additional 3 H+ to transport Pi OUTLINE: Lipid Degradation (Catabolism) FOUR stages in the catabolism of lipids: Mobilization from tissues (mostly adipose) Activation of fatty acids Transport Oxidative Phosphorylation Oxidation Energetics (–0.16 V needed for making ATP) Mitochondria Transport (2.4 kcal/mol needed to transport H+ out) Electron transport Discovery Four Complexes Complex I: NADHà CoQH2 Complex II: Succinateà CoQH2 Complex III: CoQH2à Cytochrome C (Fe2+) Complex IV: Cytochrome C (Fe2+) à H2O Chemiosmotic theory ATPase Mitchell Hypothesis Binding-Change Model Connection to the proton motive force Net ATP production Exam-2 material Regulation 1 Oxidative Phosphorylation Net Production of ATP via Catabolic Pathways TABLE 19-5 ATP Yield from Complete Oxidation of Glucose * Process Direct product Final ATP Glycolysis 2 NADH (cytosolic) 2 ATP 3 or 5a 2 Pyruvate oxidation (two per glucose) 2 NADH (mitochondrial matrix) 5 Acetyl-CoA oxidation in citric acid 6 NADH (mitochondrial matrix) cycle (two per glucose) 2 FADH2 2 GTP Total yield per glucose 15 3 2 30 or 32 If the malate/aspartate shuttle is used to transfer reducing equivalents into the mitochondrion, yield is 5 ATP. If the glycerol 3-phosphate shuttle is used, the yield is 3 ATP. a • • • Every F0 turn uses 8-17 H+ Every turn gets 3 ATP Additional 3 H+ to transport Pi * What is the yield for c17? • This Table assumes F0 is c9 and uses 9 H+ per turn • Additional 3 H+ to transport Pi needs 12 H+ per 3 ATP • This is 4 H+ per ATP • NADH pumps10 H+, so 10/4 = 2.5 ATP/NADH oxidized Oxidative Phosphorylation • Primarily regulated by substrate Regulation availability – NAD+ and ADP/Pi • Inhibition of OxPhos leads to accumulation of NADH. – causes feedback inhibition cascade up to PFK-1 in Glycolysis Local feedback inhibition – Succ-CoA, Citrate, Ac-CoA,\ and Glc6P. • Inhibitor of F1 (IF1) – prevents hydrolysis of ATP during low oxygen – IF1 only active at lower pH in matrix, encountered when electron transport is stalled (i.e., low oxygen) 2 Oxidative Phosphorylation UNCOUPLING Chemically uncoupling ET and ATP biosynthesis: Recall: • In addition to chemical uncouplers (DNP & FCCP), there are times when uncoupling is needed physiologically • Uncoupling protein 1 (UCP-1) in babies • Hibernating animals Summary:Oxidative Phosphorylation We learned that: • the reduced cofactors pass electrons into the electron-transport chain in mitochondria • stepwise electron transport is accompanied by the directional transport of protons across the membrane against their concentration gradient • the energy in the electrochemical proton gradient drives synthesis of ATP by coupling the flow of protons via ATP synthase to conformational changes that favor formation of ATP in the active site 3 End of material for Exam 2 Lipid Degradation 4