Biomedical Engineering Reference
In-Depth Information
the principal storage form of phosphorus in plants.
6
The inositol phosphates,
especially myo-inositol triphosphate (IP3), are also abundant in human cells,
and their function is to recruit Ca
2+
from storage organelles.
7
In the nervous
system, IP3 serves as a second messenger, with the cerebellum containing the
highest concentration of IP3 receptors.
7
IP5 is abundant in the erythrocytes of
birds, where it is the functional homologue of the 2,3 BPG in humans.
8
IP5
binds
more
tightly
to
deoxyhemoglobin
than
to
oxyhemoglobin,
thereby
allosterically reducing the hemoglobin oxygen affinity.
8
IP6, although not utilised for this function in nature, has the same allosteric
characteristics when binding to hemoglobin.
9
Our investigations into this
molecule were based on our interest in it as an allosteric effector, with as aim
the study of IP6 with human hemoglobin (see Section 10.3). A new interest into
IP6 derives from the fact it has effective anti-cancer action against a variety of
experimental tumours.
10
IP6 is also a ligand binder by itself: it binds protons to its phosphate groups
(see Figure 10.1). IP6 increases its charge from 0 to 212 units upon full
deprotonation. It should therefore be not surprising that its proton-binding
characteristics, or pH titration, are highly anti-cooperative.
11
That is, it takes
much free energy to dissociate the last protons away from the high electrostatic
field, or in other words, it costs much free energy to move IP6 in a highly
unfavourable state of electrostatic repulsion. The anti-co-operativity in the pH
titration is shown in Figure 10.2, deprotonating the molecule takes more than
five pH units, as compared to the normal three units for a one-proton binding
event.
Figure 10.2
Potentiometric pH titration of IP6. Adapted from ref. 11.
