1. Krebs cycle

2. Krebs Cycle (Citric acid cycle) Series of 8 sequential reactions Matrix of the mitorchondria Synthesis of 2 ATP Generation of 8 energetic electrons 4 CO 2 molecules

3. Krebs Cycle

4. Reaction 1: Condensation 2-carbon acetyl group from acetyl- CoA Joins with oxaloacetate a four- carbon molecule Forms a six-carbon molecule, citrate.

5. Reaction 2: Isomerization Hydroxyl (-OH) group of citrate is repositioned A water molecule is removed from one carbon Water is added to another carbon on the same citrate molecule. As a result, an –H group & an –OH group change positions. Product is isocitrate-an isomer of citrate

6. Reaction 3: The First Oxidation First energy yielding step of cycle Isocitrate undergoes an oxidative decarboxylation reaction. First: isocitrate is oxidized Yielding a pair of electrons Associated with a proton as a hydrogen atom Reduces NAD + to NADH.

7. Reaction 3: The First Oxidation Second: oxidized intermediate is decarboxylated Central carbon atom splits off to form CO 2 Yields a five-carbon molecule α-ketoglutarate

8. Reaction 4: The Second Oxidation α-ketoglutarate is decarboxylated Looses a CO 2 CoEnzyme A is attached Forms succinyl-CoA Two electrons are extracted Associated with a proton as a hydrogen atom Reduce another molecule of NAD+ to NADH.

9. Reaction 5: Substrate-Level Phosphorylation Linkage between the four-carbon succinyl group & CoA is a high-energy bond. Bond is cleaved Energy released drives phosphorylation of GDP, forming GTP. GTP is readily converted into ATP, Succinate 4-carbon fragment that remains

10. Reaction 6: Third Oxidation Succinate is oxidized to fumarate FAD + is electron acceptor. FAD + remains in a part of the inner mitochondria membrane FADH 2 (reduced) is used in electron transport chain in the membrane

11. Reactions 7 & 8: Regeneration of Oxaloacetate. A water molecule is added to fumarate, Forms malate Malate is then oxidized Yields oxaloacetate a four-carbon molecule Two electrons Associated with a proton as a hydrogen Reduce a molecule of NAD + to NADH.

12. Reactions 7 & 8 : Regeneration of Oxaloacetate. Oxaloacetate Molecule that began the cycle Combines with another two-carbon acetyl group from acetyl-CoA Reinitiate the cycle.

13. Fig. 9-12-1 Acetyl CoA Oxaloacetate CoA—SH 1 Citrate Citric acid cycle

14. Fig. 9-12-2 Acetyl CoA Oxaloacetate Citrate CoA—SH Citric acid cycle 1 2 H2OH2O Isocitrate

15. Fig. 9-12-3 Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Citric acid cycle Isocitrate 1 2 3 NAD + NADH + H +  -Keto- glutarate CO2CO2

16. Fig. 9-12-4 Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Isocitrate NAD + NADH + H + Citric acid cycle  -Keto- glutarate CoA—SH 1 2 3 4 NAD + NADH + H + Succinyl CoA CO2CO2 CO2CO2

17. Fig. 9-12-5 Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Isocitrate NAD + NADH + H + CO2CO2 Citric acid cycle CoA—SH  -Keto- glutarate CO2CO2 NAD + NADH + H + Succinyl CoA 1 2 3 4 5 CoA—SH GTP GDP ADP P i Succinate ATP

18. Fig. 9-12-6 Acetyl CoA CoA—SH Oxaloacetate H2OH2O Citrate Isocitrate NAD + NADH + H + CO2CO2 Citric acid cycle CoA—SH  -Keto- glutarate CO2CO2 NAD + NADH + H + CoA—SH P Succinyl CoA i GTP GDP ADP ATP Succinate FAD FADH 2 Fumarate 1 2 3 4 5 6

19. Fig. 9-12-7 Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Isocitrate NAD + NADH + H + CO2CO2  -Keto- glutarate CoA—SH NAD + NADH Succinyl CoA CoA—SH PP GDP GTP ADP ATP Succinate FAD FADH 2 Fumarate Citric acid cycle H2OH2O Malate 1 2 5 6 7 i CO2CO2 + H + 3 4

20. Fig. 9-12-8 Acetyl CoA CoA—SH Citrate H2OH2O Isocitrate NAD + NADH + H + CO2CO2  -Keto- glutarate CoA—SH CO2CO2 NAD + NADH + H + Succinyl CoA CoA—SH P i GTP GDP ADP ATP Succinate FAD FADH 2 Fumarate Citric acid cycle H2OH2O Malate Oxaloacetate NADH +H + NAD + 1 2 3 4 5 6 7 8

21. Krebs Cycle 2 pyruvate from glycolysis 6 CO 2 molecules 2 ATP molecules 10 electron carriers 8 NADH molecules 2 FADH 2

22. Figure 9.16b 2 FADH 2 6 NADH CITRIC ACID CYCLE PYRUVATE OXIDATION 2 Acetyl CoA + 2 ATP 2 NADH

23. Glycolysis & the Krebs cycle produced a large amount of electron carriers. These carriers enter the electron transport chain Help produce ATP

24. Electron transport chain Energy captured by NADH is not harvested all at once. Transferred directly to oxygen 2 electrons carried by NADH are passed along the electron transport chain if oxygen is present.

25. Oxidative phosphorylation Formation of ATP 1. Electron transport chain Series of molecules embedded in the inner membranes of mitochondria. Electrons are delivered at the top of the chain Oxygen captures them at the bottom

26. Electron transport chain Large protein complexes Smaller mobile proteins Smaller lipid molecule called ubiquinone (Q)

27. Fig. 9-13 NADH NAD + 2 FADH 2 2 FAD Multiprotein complexes FAD FeS FMN FeS Q  Cyt b   Cyt c 1 Cyt c Cyt a Cyt a 3 IVIV Free energy (G) relative to O 2 (kcal/mol) 50 40 30 20 10 2 (from NADH or FADH 2 ) 0 2 H + + 1 / 2 O2O2 H2OH2O e–e– e–e– e–e–

28. Electrons move towards a more electronegative carrier Electrons move down an electron gradient This flow of electron creates the active transport of protons out into the matrix

29. 2. Chemiosmosis Protons diffuse back into the matrix through a proton channel It is coupled to ATP synthesis

31. Electron transport chain Carbon monoxide & cyanide affect the electron transport in the mitochondria Shuts down the production of ATP Cell dies as does the organism

33. Fermentation Anaerobic conditions H atoms (NADH) are donated to organic compounds Regenerates NAD+

34. Figure 9.17a 2 ADP + 2 P i NAD + + 2 H + GLYCOLYSIS Glucose 2 ATP 22 2Ethanol2 Acetaldehyde 2 Pyruvate (a)Alcohol fermentation 2 CO 2 NADH

35. Figure 9.17b 2 ADP + 2 P i NAD + + 2 H + GLYCOLYSIS Glucose 2 ATP 2 2 Lactate (b)Lactic acid fermentation NADH 2 Pyruvate 2

38. Proteins and fats Other organic molecules are an important source of energy.

39. Proteins First are broken down to amino acids Each amino acid undergoes a process called deamination. Removal of the nitrogen containing side group After a series of reactions the carbon groups enter the either glycolysis or the krebs cycle

40. Fats Fats are broken down to FA & glycerol Each FA undergoes β oxidation Conversion of the FA to several acetyl groups These groups combine with coenzyme A to make acetyl-CoA

41. Regulation Control of the glucose catabolism Occurs at 3 key points 1. Control point in glycolysis Enzyme phosphofructokinase Catalyzes the conversion of fructose 6-phosphate to fructose 1,6 bisphosphate.

42. Regulation High levels of ATP inhibit phosphofructokinase ADP & AMP activate the enzyme Low levels of citrate also activate the enzyme

43. Regulation 2. Pyruvate dehydrogenase Enzyme that removes CO 2 from pyruvate. High levels of NADH will inhibit its action

44. Regulation 3. High levels of ATP inhibit the enzyme citrate synthetase Enzyme that starts the Krebs cycle Combines Acetyl-CoA with oxaloacetate to make citrate

45. Evolution Krebs cycle & ETC function only in aerobic conditions Glycolysis occurs in both Early bacteria used only glycolysis to make ATP before O 2 All kingdoms of life use glycolysis Occurs outside the mitochondria Indicates mitochondria developed later.