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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?.

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slide1

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

slide2

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

slide4

O

O

H

H

O

O

NO2

NO2

NO2

NO2

NO2

NO2

NO2

NO2

2,4-dinitrophenol – a proton ionophore

H+

H+

Inner Membrane

Matrix

Text p519

slide5

Thermogenin

Brown Adipose

Tissue

Uncoupling

a proton gradient

from FOF1 ATPase

Produces Heat!

staying alive energy wise
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 245.9 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)
slide7

Control

of

Oxidative phosphorylation

What makes us breathe faster?

How does ATP synthesis in the mitochondria adjust to the needs of the cell?

slide8

[ATP]

[ADP][Pi]

WHAT IS THE ATP MASS ACTION RATIO?

= ATP mass action ratio

High: Energy sufficient, Signifies high ATP

Low: Energy debt, Signifies high ADP or low ATP

HIGH Mass Action Ratio:

Oxidized cytochrome C [C3+] is favored

Cytochrome oxidase is low because of low C2+

O2 uptake low

LOW Mass Action Ratio:

Reduced cytochrome C [C2+] is favored

Cytochrome oxidase stimulated because of high C2+

Oxygen uptake high

slide9

Equilibrium

½NADH + Cyt c (Fe3+) + ADP + Pi

½ NAD+ + Cyt c (Fe2+) + ATP Go’= 0

[c2+]

½

[NAD+]

[c3+]

[NADH]

ATP

[ADP][Pi]

Control of Oxidative Phosphorylation

Keq =

[ATP] can control its own production

Cytochrome c oxidase step is irreversible and is controlled by

reduced cytochrome c (c2+)

Because of equilibrium, concentration of c2+ depends on

[NADH]/[NAD+] and [ATP]/[ADP][Pi]

slide10

ATP mass action ratio

[ADP][Pi]

[ATP]

[c2+]

½

[NADH]

[c3+]

[NAD+]

Control of Cytochrome Oxidase (Cox)

Keq

=

NADH

Mass Action ration

equilibrium

Stimulates Cox

[c2+]/[c3+]

NADH

equilibrium

Stimulates Cox

ADP

[c2+]/[c3+]

equilibrium

Stimulates Cox

ATP

[c2+]/[c3+]

equilibrium

Suppresses Cox

Cytochrome oxidase controls the rate of O2 uptake which

means this enzyme determines how rapidly we breathe.

slide11

Oxygen Radicals

Unpairedelectron

.

.

.

.

O :: O

.

.

.

.

= O2-

Partially reduced oxygen species

Molecular Oxygen

.

.

.

.

O2

O :: O

.

.

.

.

O2

Octet Rule

Superoxide Anion

slide12

What is aFreeRadical?

Any chemical species with one of more unpaired

electrons…….

Highly Reactive

Powerful Oxidant

Short half life (nanoseconds)

Can exist freely in the environment

slide13

.

H

.

O2

.

OH

.

NO

EXAMPLES OF FREE RADICALS

Hydrogen atom

Superoxide (oxygen centered)

Hydroxyl radical (most reactive)

Nitric Oxide

slide14

PRO-OXIDANTS

(Generates Free Radicals)

Generates hydroxyl radical

Fe2+ + H2O2

Ascorbic acid + Fe2+

Generates hydroxyl radical

Paraquat

Generates superoxide radical

Generates superoxide radical

Agent Orange

Generates hydroxyl radical

Ozone

slide15

WHAT ARE ANTIOXIDANTS?

ENZYMES

O2-

Superoxide dismutase

Catalase

H2O2

R-OOH

Peroxidases

VITAMINS

Vitamin E (tocopherols)

Beta Carotene (pro-vitamin A)

Vitamin C

quiz 1

Quiz 1

4 Questions

5 Points

slide17

1. Other than Fructose-6-PO4 and Fructose-1,6 bisPO4, name another phophate ester of fructose.

Fructose 1-PO4 or Fructose 2,6-bisPO4

2. Other than glycerate-1,3 bisPO4, name another high energy intermediate derived from glucose in glycolysis.

PEP

3. Name a compound in the Krebs cycle, which when oxidized to CO2 and H2O gives rise to 30 ATPs

Succinyl-CoA

4. Name 2 pentoses that are found in the pentose phosphate pathway.

Ribose-5-PO4 Ribulose-5-PO4 Xylulose-5-PO4

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