CLINICAL CASES
455
D efinitions
Calcitonin: A polypeptide hormone of 32-amino acid residues that is syn-
thesized in the parafollicular cells (C cells) of the thyroid gland.
Calcitonin is secreted in response to elevated blood Ca2+ levels.
IP3: Inositol 1,4,5-trisphosphate (inositol trisphosphate); a second messen-
ger released by the action of phospholipase C on phosphatidylinositol
4,5-bisphosphate (PIP2). IP3 will bind to receptors on the endoplasmic
reticulum (ER) to cause the rapid efflux of Ca2+ from the ER into the
cytoplasm.
Phosphoinositide cascade: The sequence of events that follow the binding
of a hormone to a receptor that acts via a Gq-protein. Hormone binding
to the Gq-coupled receptor activates phospholipase C, which cleaves
PIP2 to IP3 and diacylglycerol, both of which are second messengers.
PTH: Parathyroid hormone; an 84-amino acid polypeptide hormone that is
synthesized in the parathyroid gland and is secreted in response to
low blood Ca2+ levels. PTH acts to increase the Ca2+ concentration in
the blood by stimulating osteoclast formation and activity, thus releasing
bone calcium and phosphate into the blood.
Vitamin D: Vitamin D3, a secosteroid (a steroid in which one of the rings has
been opened) formed by the action of UV light on 7-dehydrocholesterol.
The active form of vitamin D is the hormone 1,25-dihydroxycholecalciferol
(calcitriol), formed in the kidney in response to elevated PTH levels. It
binds to nuclear receptors in intestine, bone, and kidney to activate the
expression of calcium-binding proteins.
D ISC U SSIO N
Owing to the critical importance of calcium ion in a wide range of physiologic
processes,
blood
calcium
ion
concentrations
are
tightly
regulated.
Hypocalcemia rapidly leads to muscle spasm, tetany, cardiac dysfunction,
and numerous other symptoms. About half of the calcium ions in blood are
bound to protein, and half are in the unbound state. Blood calcium ion con-
centrations are close to 1 mM, a value 10,000 times higher than free calcium
ion concentrations in the cytoplasm. Normal calcium and phosphate concen-
trations in blood are near their solubility limit. Thus elevation in these levels
leads to precipitate formation and organ damage.
Intracellular calcium ion is largely sequestered within mitochondria
and the lumen of the endoplasmic reticulum. Inositol trisphosphate (IP3)—
a second messenger of hormones that acts via stimulation of the phospho-
inositide cascade (Figure 51-1)—binds its receptor on the endoplasmic
reticulum membrane, triggering a rapid efflux of calcium ion from this intra-
cellular store into the cytoplasm. The calcium-binding protein calmodulin
senses fluctuations in intracellular calcium ion concentration by altering its
conformation, thus influencing activities of its numerous enzyme ligands,
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