A simplified illustrated View of Oxidative Phosphorylation on the inner Mitochondrial Membrane by Peter Gauthier

Peter Gauthier, Ph.D. Dept. Science (retired) Mount Saint Marys College Emmitsburg, MD 21727

Email: peterspond@roadrunner.com

Abstract

According to the Chemiosmotic Theory, the oxidation of the intermediates of the electron transport chain results in the establishment of a proton gradient across the inner membrane of the mitochondrion. This gradient is thought to be the source of energy for oxidative phosphorylation. The following series of diagrams represents a mechanism whereby oxidative phosphorylation can occur. Most of the elements are implicitly included in the Chemiosmotic Theory, but are not explicitly illustrated in this fashion. The following series of diagrams are seen therefore, as a simplified explanation of the mechanism for the process of oxidative phosphorylation.

Symbols used in this manuscript: O- O| | Adenine-Ribose-CH2-O-P-O-P-O|| || O O O| HO-P-O|| O

ADP3-

P2-

Definitions: Inner Membrane: Innermost membrane of the mitochondrion which envelops the Matrix.

Matrix: The inner compartment of the mitochondrion.

Figure 1 The Resting Mitochondrial Membrane

Intermembrane space

H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+

Inner Membrane

ATPsynthetase

Matrix

ADP3-

P2-

Legend:

ATP Synthetase is seen to consist of:

a.

A blocking site designated X. In the resting configuration, this segment of the protein blocks the membrane channel, and prevents the movement of H+ to the inner matrix. An active site designated Y, which has two binding sites, one for ADP3and one for P2-.

b.

Figure 2 Binding of two anions to the Active Site

Intermembrane space

H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+

Inner Membrane

ATPsynthetase
P2-

Matrix

Y
ADP3-

Legend:

Binding of two anions, ADP3- and P2-, to the Active Site of ATPsynthetase.

The binding of both anions to the active site brings about changes in the conformation of ATPsynthtase blocking site as illustrated in Figure 3.

Figure 3 Changes in the Conformation of the Blocking Site.

Intermembrane space

H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+

Inner Membrane

ATPsynthetase
P2-

Matrix

Y
ADP3-

Legend: Change in the Conformation of the Blocking Site. This conformational change of the Blocking site brings about an opening of the channel pore, which increases the porosity of the membrane to H+ at this position of the membrane, allowing the protons to move with the concentration gradient through the open pore into the matrix.

Figure 4 Movement of Hydrogen ions with the concentration gradient

Intermembrane space

H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+

Inner Membrane

H+ H+ H+ H+ H+ H+ H+

ATPsynthetase
P2-

Matrix

Y
ADP3-

Legend: Movement of Hydrogen ions with the concentration gradient The open channel provides a path for the movement of Hydrogen ions from the intermembrane space into the channel. In the process, the ions alter the environment of the two anions, P2- and ADP3-.

Figure 5

Formation of ATP at the active site

Intermembrane space

H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+

Inner Membrane

H+ H+ H+ H+ H+ H+ H+ H+ H+

ATPsynthetase
H+

Matrix P Y
ADP H+

Legend: Formation of ATP at the active site The reaction of ADP and P for the formation of the terminal anhydride is promoted by: a. The energy provided by the movement of H+ with the concentration gradient. b. The positioning of the molecules on the ATPsynthetase active site. c. The suppression of ionization of both ATP3- and P2- in this acidic medium, created by the movement of H+ in the immediate vicinity of the reacting molecules. d. The lessening of repulsion results in less electrostatic opposition to the combining molecules so that sharing of electrons between valence shells is facilitated. Suppression of ionization occurs as follows, with the subsequent formation of the terminal anhydride of ATP. ADP3- + P2- + 5H+ ------------> ADP + P -----------> ATP

Figure 6 Reestablishing the Resting Membrane Potential

Intermembrane space

H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+

Inner Membrane

ATPsynthetase

Matrix

ATP

Legend:

Consequences of anhydride formation: The formation of ATP promotes the following sequence of events. a. A precipitous decrease in the affinity of ATP synthetase for ATP. b. Release of ATP from the enzymes active site subsequent to the loss of affinity c. The release of ATP results in an allosteric change in the Blocking Site whereby it regains its original conformation. This results in a closing of the channel, which makes the inner membrane once more impermeable to H+. d. The resting membrane potential is then reestablished and the affinity of the Active Site for P2- and ADP3- is restored.