Chapter 14. Energy conversion: Energy & Behavior

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1 Chapter 14 Energy conversion: Energy & Behavior

2 Why do you Eat and Breath? To generate ATP Foods, Oxygen, and Mitochodria

3 Cells Obtain Energy by the Oxidation of Organic Molecules Food making ATP making

4 Energy carriers

5 Why ATP is useful? 1) ATP + H2O ADP + Pi 2) Energy states for Storage and transfer

6 Why ATP is useful? E0 Food molecule ATP + H2O ADP + Pi G = -7.3 kcal/mole Free energy for other reactions

7 How ATP can be made? 1) Glycolysis: 2 per 1 glucose 2) Oxidative phosphorylation: 32 per 1 glucose Which one is more faster? Which one is more efficient?

8 Mitochondria as a power plant

9 Mitochondria Inner membrane (cristae structure) Outer membrane Matrix

10 Mitochondria

11 Mitochondria The human mtdna -contains just 37 genes. -These are mostly trnas, -Some of the proteins of oxidative phosphorylation: 7/27 of Complex I 0/4 of Complex II 1/9 of Complex III 3/13 of Complex IV 2/12 of Complex V

12 Designs for ATP synthesis Chemiosmosis Chemiosmosis is the name given to the generation of ATP from a proton gradient. It occurs in all living things: Energy Potential energy kinetic energy

13 Designs for ATP synthesis Photosynthetic archaea Purple proteobacteria Chloroplasts Mitochondria

14 A Design for ATP synthesis: Oxidative phosphorylation Pyruvate CO2 + NADH NADH + O2 ATP + H2O

15 A Design for ATP synthesis: Oxidative phosphorylation Electron transport chain Cytochrome b-c1 complex NADH dehydrogenase Succinate dehydrogenase Cytochrome reductase ATP-synthase

16 Oxidative phosphorylation

A design for ATP synthesis The electron transport chain is embedded in the inner

It consists of four large protein complexes, and two smaller mobile carrier proteins.

It initiates the electron transport chain by donating electrons to NADH dehydrogenase

At the same time, the complex also pumps two protons from the matrix space of the

17 A design for ATP synthesis The electron transport chain is embedded in the inner membrane of the mitochondria. It consists of four large protein complexes, and two smaller mobile carrier proteins. NADH is the electron donor in this system. It initiates the electron transport chain by donating electrons to NADH dehydrogenase (blue). NADH donates two electrons to NADH dehydrogenase. At the same time, the complex also pumps two protons from the matrix space of the mitochondria into the intermembrane space. The two electrons are now transferred to the mobile carrier protein known as ubiquinone. Ubiquinone transports the electrons, two at a time, to the next complex in the chain.

18 A Design for ATP synthesis: High energy electron carrier nicotinamide adenine dinucleotide -Oxidation-reduction reactions; -Carry high-energy electrons and hydrogen atoms; -NAD + and NADP + -Each pick a packet of energy: 2 high-energy electrons + proton H + Get reduced to NADH (catabolic reactions) and NADPH (anabolic reactions)

19 A Design for ATP synthesis: High energy electron carrier Flavin mononucleotide

20 A Design for ATP synthesis: High energy electron carrier Coenzyme Q: ubiquione -Ferries electrons from complexes I and II to complex III. -Long hydrophobic chain: UQ UQH 2 can migrate actually dissolved within the membrane. semiubiquinone is dangerous is that is can generate superoxide radicals, which are hugely oxidising free-radicals. UQH + O 2 UQ + H + + O 2 2O 2 + 2H + O 2 + H 2 O 2 Fe 2+ + H 2 O 2 Fe 3+ + OH + OH Mitochondria therefore contain superoxide dismutase and glutathione (GSH) peroxidase to cope with these agents of oxidative stress. 2GSH + H 2 O 2 GSSG + 2H 2 O

21 A design for ATP synthesis Ubiquinone (pink) delivers two electrons at a time to cytochrome b-c1 (red). As each electron makes its way through the complex, a hydrogen ion, or proton, is pumped from the matrix space of the mitochondria into the intermembrane space, helping to maintain the proton gradient. After affecting the pumping of a proton across the membrane, the electron leaves cytochrome b-c1 and enters the mobile carrier protein, cytochrome c (purple).

22 Cytochrome b and c Prosthetic group Bound from to protein Cyt. b Cyt. C

23 Cytochrome b and c complex

A design for ATP synthesis The mobile carrier protein cytochrome c (purple) transfers

Four electrons must be transferred to the oxidase complexes in order for the next major

The next major event is the reaction of the four electrons, a molecule of O2 (oxygen),

24 A design for ATP synthesis The mobile carrier protein cytochrome c (purple) transfers electrons, one at a time, to cytochrome oxidase (orange). Four electrons must be transferred to the oxidase complexes in order for the next major reaction to occur. The next major event is the reaction of the four electrons, a molecule of O2 (oxygen), and eight protons. The reaction results in the pumping of four hydrogen ions across the inner membrane into the intermembrane space, and the release of two H20 (water) molecules into the matrix space.

25 Cytochrome oxidase complex Gating of proton and water transfer in the respiratory enzyme cytochrome c oxidase. // Proc Natl Acad Sci USA 2005, 102,

26 How electrons are sequentially transferred? Complex I, II UQ (CoQ) III CytC IV

A design for ATP synthesis ATP synthase accepts one proton from the intermembrane space and releases a different proton into the matrix space to create the energy it needs to synthesize ATP.

27 A design for ATP synthesis ATP synthase accepts one proton from the intermembrane space and releases a different proton into the matrix space to create the energy it needs to synthesize ATP. It must do this three times to synthesize one ATP from the substrates ADP and Pi (inorganic phosphate). With the supply of NADH exhausted, the electron transport chain can no longer maintain the proton gradient that powers ATP synthase, and ATP synthesis comes to a stop.

ATP synthase Preventing head rotation As protons flow through the a/b subunits (the stator) of F O, they force the ring of twelve c subunits (the rotor) in the membrane to rotate.

28 ATP synthase Preventing head rotation As protons flow through the a/b subunits (the stator) of F O, they force the ring of twelve c subunits (the rotor) in the membrane to rotate. F 1 This rotation is transmitted to the γ/ε subunits (the stalk) of F 1, which change the conformation of the α/β subunits (the headpiece) of F 1, making ADP and phosphate react to form ATP inside the β subunits. The headpiece is prevented from rotating by the binding of δ to the a/b stator, which is itself firmly anchored in the membrane. F O

29 ATP synthase

30 A design for ATP synthesis

31 Energy states should be regulated. Which one is signaling molecule? AMP AMPK

32 How can we measure cytochrome oxidase activity Overall oxidative phosphorylation This means proportional to cytochrome oxidase activity

33 Energy states should be regulated. Which one is signaling molecule?

34 Energy states should be regulated. Which one is signaling molecule? ATP ADP AMP

35 Obesity at cellular level? Beta-oxidation Glycolysis Oxidative phosphorylation NADH or NAD+?

36 Low energy state (diet, exercise) NAD+ high Stimulates -beta-oxidation of fatty acids -Mitochondria biogenesis Inhibits -Accumulation of lipids -Mitochondrial degeneration

37 High energy state (obesity) NADH high Inhibits -beta-oxidation of fatty acids -Mitochondria biogenesis Stimulates -Accumulation of lipids -Mitochondrial degeneration

38 NAD+ dependant signaling pathways NAD+ NAD homeostasis cadpr Cofactor & Substrate Transcription Factor RyR (ER) Sirt1-7 Activation CtBP & RIP140 Inhibition Enzyme Activity Control Ca 2+ mobilization Ca/CaM (CaMPKKß AMPK activation) SERCA TCA cycle enzymes Activation PGC1α enos Insulin Signaling (IRS-2, PTP1B control) Aldose reductase 11-ß- HSD NAD(P)H Oxidase

39 If you do aerobic exercise AMP NAD + /NADH LKB1 (AMKK) CamKK AMPK abg Pi ACC ACC Pi Acetyl-CoA Malonyl-CoA Fatty Acyl-CoA CPT1 Fatty Acid Oxidation

40 NAD+ activates SIRT pathways SIRT: NAD-dependant deaceylase Calorie restriction NAD+

41 ATP case study H NH NADH 2 NAD + O H H N -O P O O OAMP H H H OH H OH H O H Oxidation NQO1 O H -O P O O OAMP H MB12066 MB12066 H2 H N + H H H OH OH O H NH 2 Cytoplasmic NAD + NADH Anti-oxidation

42 Effects of NAD+ DIO* = Diet Induced Obesity control vehicle MB12066

43 NAD+ effects on body fat Lean Untreated Vehicle MB Fat area = 5.6% Fat area =54.4 % Fat area = 48.7% Fat area = 12.1% Fat area = 10.3% Fat area = 56.3% Fat area = 57.0% Fat area = 26.8 %

44 NAD+ effects on body fat Control MB12066 TG Oil red Staining

45 Relative mtdna (mtdna/genomic DNA) NAD+ effects on muscles Soleus, Vehicle (8 wks) Soleus, MB (8 wks) nm X10,000 X10, Vehicle MB X25,000 X25,000 Number of mitochondria increase

46 Mitochondria numbers Mitochondrial / area numbers /cell NAD+ effects on Liver mitochondria 150 Dio (56day) Liver in Dio (56day) Veh MB X10, Vehicle MB X25,000 Vehicle MB Liver, Vehicle (8 wks) Liver, MB (8 wks)

Type II b ( 지근 ) ( 속근 ) Type II b Data Table-2 60 300 * Veh 40 20 * * * * * ** * * * * ** *

47 Vo2 (ml/kg/min) VO 2 (ml/kg/min) Energy expenditure (Kcal/kg/day) NAD+ effects on muscle type Soleus, Vehicle (8wks) Soleus, MB (8wks) Type I Type II a Data Table-7 Type I, II a > Type II b ( 지근 ) ( 속근 ) Type II b Data Table * Veh * * * * * ** * * * * ** * * * ** * ** Lipid catabolism Is increased MB Vehicle MB 0 9pm 1am 5am 9am 0 Vehicle MB

48 Mitochondrial fusion and fission Young Aged 노화

49 Chloroplast Home work: Summarize differences Between Mito. Vs. Chlroro

Electron transport chain chapter 6 (page 73) BCH 340 lecture 6

Electron transport chain chapter 6 (page 73) BCH 340 lecture 6 The Metabolic Pathway of Cellular Respiration All of the reactions involved in cellular respiration can be grouped into three main stages