Chemistry Reference
In-Depth Information
Chapter 11
Calcium
e
Cellular Signalling
Introduction e Comparison of Ca
2D
and Mg
2D
215
The Discovery of a Role for Ca
2D
Other than as a Structural Component
215
An Overview of Ca
2D
Regulation and Signalling
216
Ca
2D
and Cell Signalling
225
2D
2D
INTRODUCTION e COMPARISON OF CA
AND MG
How does Nature achieve the high degree of selective binding of Ca
2
þ
by biological ligands compared to Mg
2
þ
? The
differences in structure, thermodynamic stability, and reaction rates all stem from the difference in their ionic radii
(Mg
2
þ
,0.6
˚
;Ca
2
þ
,0.95
˚
) measured in an octahedral oxygen donor environment. The Mg
2
þ
ion is strictly octa-
hedral with Mg
O distances of around 2.05
˚
, whereas the larger Ca
2
þ
ion, like Na
þ
and K
þ
, has an irregular
coordination geometry, bond angle, bond distance, and coordination number (7
e
e
10) with Ca
e
Odistancesof
2.8
˚
. In the case of the smaller Mg
2
þ
, the central field of the cation dominates the coordination sphere, whereas
in the larger cations the second and possibly even the third, coordination spheres, have a more important influence
resulting in irregular structures. This also enables Ca
2
þ
,unlikeMg
2
þ
ion to bind to a large number of centres at once.
Further, the kinetics of Ca
2
þ
binding are quite different withwater exchange rates close to the collision diffusion limits
of 10
10
s
1
, unlike much slower rates of 10
6
s
1
for Mg
2
þ
.Ca
2
þ
can interact with neutral oxygen donors, like
carbonyls and ethers, unlike Mg
2
þ
in aqueous media, as well as with anions, which avoids competition with Na
þ
.
e
2.3
2D
THE DISCOVERY OF A ROLE FOR CA
OTHER THAN AS A STRUCTURAL COMPONENT
Calcium, together with sodium, potassium, and magnesium, is one of the metals required by living systems in macro-
amounts
2% of an adult's total body weight. The biominerals that constitute teeth and
bones contain the majority of the body's calcium (about 99%). Yet, the 1%which remains within the cells and tissues
has enormous importance in the regulation of a whole series of cellular responses. Like a number of other discoveries,
it was made by serendipity, and came far too early for the scientific community to recognise the importance of the
discovery. In 1883, the English physiologist Sidney Ringer carried out a rather sloppy experiment, in which he
suspended rat hearts in a saline medium made from London tap water (notoriously 'hard' on account of its high
calcium content) and observed that they continued beating for a considerable period of time. When he repeated his
initial experiments with distilled water, the hearts stopped beating after about 20-min incubation. He subsequently
found that the addition of Ca
2
þ
to the saline solution of the distilled water allowed prolonged cardiac contraction,
establishing unequivocally that Ca
2
þ
had a role in a tissue that had neither bones nor teeth. However, we had to wait
more than sixty years before the importance of his observation that Ca
2
þ
had a real function in cellular biochemistry,
totally unrelated to its well-established structural role as a component of bones and teeth, became evident.
We now recognise that most important processes in living cells are regulated by Ca
2
þ
. As Ernesto Carafoli has
put it, 'Ca
2
þ
accompanies cells throughout their entire lifespan, from their origin at fertilisation, to their eventual
demise
e
indeed, it represents 1.5
e
as a conveyor of doom at the moment of cell death' (
Carafoli, 2002
). Indeed, Ca
2
þ
controls almost
.
