BioPHYSICAL chemistry

This reaction is highly exergonic, with a Gibbs energy difference of

−220 kJ mol−^1 under standard conditions. Much of the energy is used to

transfer protons out of the matrix into the intermembrane space. In con-

sidering the proton flow, for every pair of electrons, there are four protons

transferred by complex I, four by complex III, and two by complex IV.

Including the proton transfer with the electron transfer yields:

(6.27)

The molecular mechanisms by which each step of this net reaction pro-

ceeds is under active investigation by a number of laboratories. For each

complex, a number of cofactors are involved in multi-electron transfers

that are coupled with proton transfer. The

determination of the structures of com-

plexes II, III, and IV and the water-soluble

domain of complex I has provided the

foundation for such investigations (Xia

et al. 1997; Iwata et al. 1998; Iverson et al.

1999; Lancaster et al. 1999; Sarasta 1999;

Lange & Hunte 2002; Yankovskaya et al.

2003; Sazanov & Hinchiffe 2006). Among

the revelationsfrom these structures was

the realization that the protein surround-

ing the cofactors is not simply scaffolding.

Motion of the protein plays a critical role,

with the electron transfer between the

iron–sulfur cluster and cytochrome c 1 heme

being driven by a rocking motion of the

Rieske iron–sulfur protein (Figure 6.12;

Zhang et al. 1998; Darrouzet et al. 2001;

Berry & Huang 2003).

Research direction: ATP synthase

This strategy of overcoming endothermic reactions by coupling the reac-

tions with ATP hydrolysis is used in all living cells for the synthesis of

metabolic intermediates and cellular components. To be practical, ATP

must be available to drive these reactions. Towards this end, the transfer

of protons across the cell membrane is used to drive the synthesis of ATP

from ADP through the transfer of protons from the intermembrane space

to the matrix:

ADP +Pi+nH+intermembrane→ATP +H 2 O +nH+matrix (6.28)

NADH++→+ 11 Hmatrix++O NAD Hinterm

1

2

2e^10 + embrane+HO 2

128 PARTI THERMODYNAMICS AND KINETICS

H

H

Cytochrome b

Cytochrome

c 1

Cytochrome c 2

Rieske Fe–S

protein

Q 0

Qi

QH 2

QH 2

Q

Q

bH

bL

Fe 2 S 2

to RC

Figure 6.12
Schematic
representation of
the cytochrome bc 1
complex showing the
motion of the Rieske
iron–sulfur protein
that plays a key
role in driving the
electron-transfer
pathway. Modified
from Crofts and
Berry (1998).