Download : Water soluble hormones

: Water soluble hormones Receptor: membrane receptor
Receptor: membrane receptor
Hormone +
Recep:
Activate G‐protein (transducin) on innerside of membrane
Activate
adenylcyclase
CAMP
Third messenger
Third messenger
Phosphlipase C
DAG
Second messengers
release of ca++from ER activate protein kinase C
release of ca++from ER
activate protein kinase C
IP3
activate protein kinase A
activate protein kinase A
Ca++ +calmodulin Phosphorylation Phosphorelation
Activate protein kinase dependant on ca/calmodulin
Phosphorylation
Diseases resulting
g from receptor
p
defect:
Biosynthesis of peptide Hormones:
Parathyroid H as an example
Steps:
1. initiation ► formation of a mRNA
Specify a polypeptide larger than required one On ribosome translation
On ribosome translation
.2
2
20 aminoacyl residue (peptide)formed (signal peptide)
y
(p p
)
( g
p p
)
3. Signal peptide facilitate
‐growing polypeptide chain
‐associated mRNA
‐Ribosome to ER
Ribosome to ER
Contnued to next slide
Growth of the polypeptide continue and glycosylation if needed take place & before the formation complete signal peptide removed by peptidase
tid
db
tid
.4
Prohormone is formed (inactive)
5
By energy – requiring step (GTP) prohormone is transferred to golgi further glycosylation take place if necessary
6
Active hormone formed by peptidase
‐two peptides are formed some times both have biological function
two peptides are formed some times both have biological function
7
On signal to secrete Ca++ dependent fusion of vesicle with plasma membrane ► release of hormone
plasma membrane ►
release of hormone
8
THYROID HORMONES
Structure and biosynthesis of T3 and T4
Structure and biosynthesis of
Steps:
1‐ Iodide uptake
Iodide uptake from blood energy dependent uptake inhibited from blood energy dependent uptake inhibited
by perchlorate
2‐ iodide► free radicle I+
iodination on tyrosine molecules which present on surface of on tyrosine molecules which present on surface of 3‐
3
thyroglobulin by peroxidese on position 3 mono iodotyrosin
thereon position 5 di iodiotyrosin
4‐ by peroxidese
Coupling will take place between 2 diiodotyrisine►
will take place between 2 diiodotyrisine► T4
Or between monoand& diiodotyrosine► T3
Both T3&T4 will be on the surface of thyroglobulin
Both T3&T4 will be on the surface of thyroglobulin
Contnued to next slide
by effect of TSH 5‐
Th
Thyroglobulin transferred by
l b li t
f
d b pinocytosis
i
t i
from colloid
6‐ Thyroglobulin vesicle fuse with lysosome► proteolysis
▼
T3, T4 , mono and diiodotyrosine
7‐ T4: T3
20‐30 :1
0 30 :
T3► 3‐5 times more potent than T4
T4 deiodinase T3
In prepreferal tissue
In
prepreferal tissue
T3 T4 Prohormone true hormone
Plasma transport of T3 and T4
Plasma transport of T3 and T4
> 99.5% are bound •
Binding proteins: d
•
Thyroxine‐binding globulin •
Albumin •
Precalbumin •
albumin
20 %
20 %
35 %
prealb 10
27
TBG T4 70
T4 70
T3 38
Protein bound are biologically inactive►Reserve
g
y
Inactivation of T3 &T4
T4 deiodination T3 + rT3
T3, rT3 deiodinated bis ‐iodothyronines
Transport of T3 and T4
In the plasma, T3 and T4 are mostly , about 99.5%,
bound to transport proteins.
p p
Albumin
Thyroxine-binding globulin
Prealbumin
T3
25%
75%
none
T4
10%
75%
15%
Thyroxine‐binding globulin is a special α‐
globulin of molecular weight 60,000. The
concentration in plasma is very low, 2 mg/100ml,
but it has one binding site per molecule with a
very high affinity for T4 and T3.
3. Peripheral hormone conversion 3
P i h lh
i
by conversion of T4 into active T3 or inactive
rTT3 as a response of a variety of physiologic
f
i t f h i l i
and pathologic changes and determining the
b l
balance between hormone activation and b t
h
ti ti
d
inactivation, e.g. malnutrition, liver disease,
generalized debility, pregnancy, stress and li d d bilit
t
d
steroid therapy increase rT3