Inhibitors and Uncouplers Any compound that stops electron transport will stop respiration…this means you stop breathing Electron transport can be stopped by inhibiting ATP synthesis An uncoupler breaks the connection between ATP synthesis and electron transport

What is an Uncoupler? Uncouplers break the connection between electron transport and phosphorylation Electron transport is a motor Phosphorylation is the transmission Uncouplers let you put the car in NEUTRAL

O NO 2 2,4-dinitrophenol – a proton ionophore H+H+ O NO 2 H O HO H+H+ Inner Membrane Matrix Text p519

Brown Adipose Tissue Uncoupling a proton gradient from F O F 1 ATPase Produces Heat! Thermogenin

Staying Alive Energy Wise We need 2000 Cal/day or 8,360 kJ of energy per day Each ATP gives 30.5 kJ/mole of energy on hydrolysis We need 246 moles of ATP Body has less than 0.1 moles of ATP at any one time We need to make moles of ATP Each mole of glucose yields 38 ATPs or 1160 kJ We need 7.2 moles of glucose (1.3 kg or 2.86 pounds) Each mole of stearic acid yields 147 ATPs or 4,484 kJ We need 1.86 moles of stearic acid (0.48 kg or 1.0 pound of fat)

Control of Oxidative phosphorylation What makes us breathe faster? How does ATP synthesis in the mitochondria adjust to the needs of the cell?

[ATP] [ADP][P i ] = ATP mass action ratio Low: Energy debt, Signifies high ADP or low ATP High: Energy sufficient, Signifies high ATP HIGH Mass Action Ratio: WHAT IS THE ATP MASS ACTION RATIO? Oxidized cytochrome C [C 3+ ] is favored Cytochrome oxidase is low because of low C 2+ O 2 uptake low LOW Mass Action Ratio: Reduced cytochrome C [C 2+ ] is favored Cytochrome oxidase stimulated because of high C 2+ Oxygen uptake high

ATP [ADP][P i ] [NAD + ] [NADH] ½ Keq = [c 2+ ] [c 3+ ] ½NADH + Cyt c (Fe 3+ ) + ADP + Pi ½ NAD + + Cyt c (Fe 2+ ) + ATP  G o’ = 0 Control of Oxidative Phosphorylation Equilibrium [ATP] can control its own production Cytochrome c oxidase step is irreversible and is controlled by reduced cytochrome c (c 2+ ) Because of equilibrium, concentration of c 2+ depends on [NADH]/[NAD + ] and [ATP]/[ADP][P i ]

[c 2+ ] [c 3+ ] [NADH] [NAD + ] ½ [ADP][P i ] [ATP] = Keq NADH ATP mass action ratio Mass Action ration NADH [c 2+ ]/[c 3+ ] equilibrium ADP[c 2+ ]/[c 3+ ] ATP[c 2+ ]/[c 3+ ] equilibrium Cytochrome oxidase controls the rate of O 2 uptake which means this enzyme determines how rapidly we breathe. Cytochrome oxidase controls the rate of O 2 uptake which means this enzyme determines how rapidly we breathe. Control of Cytochrome Oxidase (Cox) Stimulates Cox Suppresses Cox

O2O2 O2O2 O :: O Octet Rule..... O :: O... Molecular Oxygen = O 2 - Unpaired electron Oxygen Radicals Superoxide Anion Partially reduced oxygen species

What is a Free Radical ? Highly Reactive Powerful Oxidant Any chemical species with one of more unpaired electrons……. Short half life (nanoseconds) Can exist freely in the environment

EXAMPLES OF FREE RADICALS H. Hydrogen atom O2O2. Superoxide (oxygen centered). OH Hydroxyl radical (most reactive). NO Nitric Oxide

PRO-OXIDANTS (Generates Free Radicals) Fe 2+ + H 2 O 2 Ascorbic acid + Fe 2+ Paraquat Agent Orange Ozone Generates hydroxyl radical Generates superoxide radical

WHAT ARE ANTIOXIDANTS? ENZYMES VITAMINS Superoxide dismutase Catalase Peroxidases O2-O2- H2O2H2O2 R-OOH Vitamin E (tocopherols) Beta Carotene (pro-vitamin A) Vitamin C

Quiz 1 4 Questions 5 Points

1. Other than Fructose-6-PO 4 and Fructose-1,6 bisPO 4, name another phophate ester of fructose. 2. Other than glycerate-1,3 bisPO 4, name another high energy intermediate derived from glucose in glycolysis. 3. Name a compound in the Krebs cycle, which when oxidized to CO 2 and H 2 O gives rise to 30 ATPs 4. Name 2 pentoses that are found in the pentose phosphate pathway. Fructose 1-PO 4 or Fructose 2,6-bisPO 4 PEP Succinyl-CoA Ribose-5-PO 4 Ribulose-5-PO 4 Xylulose-5-PO 4