1. Cell Biology for Clinical Pharmacy Students MD102 Module II: Cell Functions (Lecture # 9 ) Dr. Ahmed Sherif Attia ahmed.attia.e.learning@gmail.com https://sites.google.com/site/ahmedsattia/

2. Objectives By the end of this lecture you should be familiar with: How the cells make ATP through: Glycolysis Krebs's cycle Electron transport phosphorylation

3. All organisms produce ATP by releasing energy stored in glucose and other sugars. Plants make ATP during photosynthesis. All other organisms, including plants, must produce ATP by breaking down molecules such as glucose.

4. Aerobic respiration The process by which a cell uses O 2 to "burn" molecules and release energy. The reaction: C 6 H 12 O 6 + 6O 2 >> 6CO 2 + 6H 2 O Note: this reaction is the opposite of photosynthesis. This reaction takes place over the course of three major reaction pathways Glycolysis The Krebs's Cycle Electron Transport Phosphorylation (chemiosmosis)

5. Glycolysis glyco = sugar; lysis = breaking Goal: break glucose down to form two pyruvates. Who: all life on earth performs glyclolysis. Where: the cytoplasm. Glycolysis produces 4 ATP's and 2 NADH, but uses 2 ATP's in the process for a net of 2 ATP and 2 NADH. Occurs in the presence or absence of oxygen.

6. The First Stage of Glycolysis Glucose (6C) is broken down into 2 Phosphoglyceraldehyde PGAL's (3C). This requires two ATP's.

7. The Second Stage of Glycolysis 2 PGAL's (3C) are converted to 2 pyruvates. This creates 4 ATP's and 2 NADH's. The net ATP production of Glycolysis is 2 ATP's.

9. Krebs's Cycle (citric acid cycle, TCA cycle) Goal: take pyruvate and put it into the Krebs's cycle, producing NADH and FADH 2 Where: the mitochondria There are two steps –The Conversion of Pyruvate to Acetyl CoA –The Krebs's Cycle proper In the Krebs's cycle, all of C, H, and O in pyruvate end up as CO 2 and H 2 O The Krebs's cycle produces 2 ATP's, 8 NADH's, and 2FADH 2 's per glucose molecule

10. The Conversion of Pyruvate to Acetyl CoA for Entry Into the Krebs's Cycle 2 NADH's are generated 2 CO 2 are released

11. The Krebs's Cycle 6 NADH are generated 2 FADH 2 is generated 2 ATP are generated 4 CO 2 are released

12. Therefore, for each glucose molecule that enters into the Krebs's cycle (including the preparatory conversion to Acetyl CoA), the net production of products are: 8 NADH 2 FADH 2 2 ATP 6 CO 2

14. Electron Transport Phosphorylation (Chemiosmosis) Goal: to break down NADH and FADH 2, pumping H + into the outer compartment of the mitochondria Where: the mitochondria In this reaction, the ETS creates a gradient which is used to produce ATP. Electron Transport Phosphorylation typically produces 32 ATP's

15. When glucose is oxidized during glyclolysis and Krebs's cycle, the coenzymes NAD and FAD are reduced to NADH and FADH 2

16. The electrons from NADH are transferred to the electron carrier coenzyme Q by NADH dehydrogenase and the protons are transferred across the membrane to the intermembrane space

17. Coenzyme Q carries the electrons to the bc 1 complex

18. As the electrons move from bc 1 complex to cytochrome c, more protons are moved across the membrane to the intermembrane space

19. Electrons are also transferred from FADH 2 to coenzyme Q with the protons being transferred across the membrane

20. Cytochrome c transfer electrons to cytochrome c oxidase complex which also transfers protons across the membrane to the intermembrane space

21. The cytochrome c oxidase complex transfer the electrons from the cytochrome c to oxygen which the terminal electron acceptor

22. Water is formed as the product

23. The transfer of the protons to the intermembrane space generates a proton motive force across the inner membrane of the mitochondrion. The protons renter the matrix through a channel protein known as ATP synthase ( membranes are impermeable to ions)

24. The energy derived from the movement of these protons is used to synthesize ATP form ADP and phosphate in a process called oxidative phosphorylation

25. Net Energy Production from Aerobic Respiration Glycolysis: 2 ATP Krebs's Cycle: 2 ATP Electron Transport Phosphorylation: 32 ATP (details next slide) Net Energy Production: 36 ATP!

26. Electron Transport Phosphorylation: 32 ATP –Each NADH produced in glycolysis is worth 2 ATP (2 x 2 = 4) - the NADH is worth 3 ATP, but it costs an ATP to transport the NADH into the mitochondria, so there is a net gain of 2 ATP for each NADH produced in glyclolysis –Each NADH produced in the conversion of pyruvate to acetyl COA and Krebs's Cycle is worth 3 ATP (8 x 3 = 24) –Each FADH 2 is worth 2 ATP (2 x 2 = 4) –4 + 24 + 4 = 32

27. Plant cell vs. Animal cell Animal cells and Plant cells contain mitochondria! –However, animal cells contain many more mitochondria than plant cells. Animal cells get most of their ATP from mitochondria. Plant cells get most of their ATP from the chloroplast. –The ATP generated from the mitochondria is only used when the plant cannot generate ATP directly from the light-dependent reactions.