Biomedical Engineering Reference
In-Depth Information
Problems
7.1
Among the neuroendocrine factors that affect the immune system, the pineal
hormone melatonin appears to be an important one. Melatonin receptors have
been described in human immune cells such as T-cells (
K
d
=
240 pM), human
Th2 lymphocytes from bone marrow (
K
d
=
350 pM), platelets (
K
d
=
4 nM),
2 nM), and monocytes with a
K
d
around 23 pM). Arrange these cells in the order in which melatonin stimu-
lation will be observed [6].
neutrophils (
K
d
=
132 pM), granulocytes (
K
d
=
7.2
Growth hormone receptor (GHR) antagonists are a new class of drugs, whose
development has been facilitated by an understanding of the molecular interac-
tion between GH and its class 1 cytokine receptor. Pegvisomant (B2036-PEG)
is a GHR antagonist developed for the treatment of acromegaly, a condition
usually caused by excessive GH secretion. To determine the effectiveness of
this drug, Ross [7] used a cell line and performed binding assays. Scatchard
analysis revealed that the Ka for GH and B2036 was 0.36
×
10
9
and 0.32
×
10
9
mol/L
−1
, respectively; and the binding capacity was 4
10
5
receptors/cell, respectively. If so, is the antagonist binding as good as the GH?
Show calculations.
×
10
5
and 5.5
×
7.3
The peroxisome proliferator-activated receptor (PPAR) belongs to the nuclear
receptor superfamily that plays an important role in the regulation of the stor-
age and catabolism of fats. It is known that binding of ligands to PPAR-
(one
of the subtypes) induce a conformational change. Interaction of PPAR-
γ
on
its affinity to various ligands can be modeled [8] by assuming single bind site
model as
γ
dR
(
)
where
R
represents the response units,
L
is the concentration of the ligand,
k
on
is the association rate constant and
k
off
is the dissociation rate constant. From experiments, following data for two
ligands were obtained. Using these values determine the rate constants and
equilibrium dissociation constant. Which ligand is better to inhibit the action
of PPAR-
dt
=
kLR
−
R k R
−
on
max
off
γ
?
Ligand 1 [
μ
M]
0.1
0.5
1
5
20
Response Unit
3
9
13.8
20.5
24
Ligand 2 [
μ
M]
0.1
0.5
1
5
20
Response Unit
1
3
6.5
14
17
7.4
Glucocorticoids are secreted from the adrenal glands and act as a periph-
eral effector of the hypothalamic-pituitaryadrenal (HPA)1 axis, playing an
essential role not only in energy metabolism but also in stress response and
homeostatic regulation. Glucocorticoids elicit hormone action via binding to
their cognate receptor glucocorticoid receptor (GR), which is a member of the
nuclear receptor superfamily and localizes in the cytoplasm as a latent species.
The GR is composed of a modular structure with a number of functional do-
mains, including AF-1 transactivation domain and AF-2. Specific mutations
in the GR cause selective loss of GR dimerization and
so prevent dimer-depen-
dent transactivation. Such dissociated receptors
retain the ability to oppose
