BioPHYSICAL chemistry

guanosine 5′-triphosphate (GTP). The transducin with bound GTP is
released from the rhodopsin and one of the protein subunits, the αsub-
unit, separates. This form of transducin, consisting of the αsubunit and
bound GTP, binds to phosophodiesterase and activates that enzyme,
leading to a rapid conversion of cyclic GMP (guanosine 3′,5′-cyclic mono-
phosphate, or cGMP) into GMP. The cycle is reset after the rhodopsin
returns to the original dark state with the incorporation of retinal after
the regeneration of cis-retinal by a retinal isomerase. Through this cycle,
absorption of a single photon leads to a rapid loss of cyclic GMP through
both depletion of the precursor GTP after transducin binding and by
activation of the phosophodiesterase (Figure 17.4). In a sense, the over-
all biological process can be thought of as a two-stage electronic device
that has a high-gain, low-noise character.
Why does this lead to a change in membrane potential? The membrane
potential is controlled by ligand-gated ion channels that bind cyclic GMP.
When cyclic GMP is bound, the channels are open and ions can flow
through the membrane. The rapid loss of cyclic GMP leads to a loss of
bound ligand, the channels close, ion flow stops, and the membrane poten-
tial becomes more negative. How can an animal’s eye respond quickly
to a sudden light in the eyes when the recovery by hydrolysis of GTP by
transducin is relatively slow? There are additional protein regulators in
the cell, which accelerate the hydrolysis to provide a rapid response.

Spectroscopic studies of rhodopsin

The role of retinal in the initiation of the visual process was discovered
by George Wald who won the Nobel Prize for Medicine in 1967. Retinal
is bound to rhodopsin through a protonated Schiff-base linkage, which
is formed when the aldehyde group of retinal binds with the amino group

Figure 17.4Structure of guanosine 3′,5′-cyclic monophosphate, or cyclic GMP, which serves as
the messenger in the G-protein cascade process.

CHAPTER 17 SIGNAL TRANSDUCTION 377

O

O

O

CH 2

HH

Guanine

H

HO OH

H

O P O

OOP

O

OOP

O

CH 2

3 

5 

HH

Guanine

H

OOH

H

O P

O

O

O

CH 2

HH

Guanine

H

OH OH

H

O P O

PP 1

Guanylate

cyclase

GTP Cyclic GMP 5 -GMP

cGMP

phosphodiesterase

H 2 OH

O O O