Enzyme-Linked Receptors :-

Tyrosine Kinase Receptors :

• The insulin receptor is a combination of 4 subunits held
together by Disulfide linkages : 2 alpha chains (entirely
outside the cell) and two beta chains ( penetrate the cell
membrane , protruding into the cell cytoplasm).
• when the alpha chains bind to the hormone ( insulin) ,
there will be autophosphorylation of the beta chains.
• When the beta chains are autophosphorylated , it
activates a local tyrosine kinase membranous enzyme.
• So this tyrosine kinase will phosphorylate the substrate
like: insulin-receptor substrate (IRS) that initiates a 2nd
messenger pathways which alter protein synthesis and
existing proteins  cell metabolism is changed .
• In this way Insulin directs the intracellular metabolic
machinery .
• Tyrosine kinase receptor is an example for : Enzyme-
Linked receptor .
• Insulin is secreted when there’s a high concentration of
glucose in the blood (Hyperglycemia) , so we let the
glucose inside the cell to be broken down by opening
the glucose channels
• Other function : activation of the enzymes responsible
for fat and proteins SYNTHESIS.

Leptin Receptors :
• this receptor exists as a homodimer (2 identical parts).
• leptin receptor is activated by the binding of Leptin.
• The Doctor said that this receptor is also activated by
Tyrosine kinase action ( but I am not Sure).
• Activated Leptin receptor activates JAK (Just Another
Kinase).
• Activated JAK : * activation of enzymes which will lead
to some physiological effects , * or it will phosphorylate
a STAT ( Signal Transducer and Activator of
Transcription ) , an activated STAT will reach and enter
the nucleus , then it will bind to a specific gene altering
it .

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So Tyrosin Kinase coupled receptor and Leptin receptor are
examples of Enzyme-Linked Receptors .

The difference between Ionotropic and Metatropic receptors.

(refer to the doctor’s slides).

Epinephrine can act through two second messenger

systems :
 BETA : first EPI stimulates the beta receptors , that will
activate Adenylate Cyclase converting ATP to cAMP ,
cAMP activates protein kinase A.

 ALPHA : when EPI stimulates the alpha receptors , it

increases the cell membrane permeability for Ca++ ,
then Ca++ binds to Calmodulin (it can bind 4 atoms of
Ca++) which activate the protein kinase B .

LIPID-SOLUBLE HORMONES
 Cross the membrane
 Bind to its receptor which it could be in the cytoplasm or
within the nucleus
 That affects the Transcription of certain genes , different
mRNA , different proteins being synthesized
 Like Aldosterone , aldosterone’s receptor are in the
distal convulated tubule of the kidney , so it increases
the membrane permeability for Na+ which leads to re-
absorption by opening the Na+ channels , this process
takes 45 min at least (SLOW).
 The termination of this process is by decreasing the
amount of the hormone or destroying it

Nuclear Hormone Receptors :

 Steroid receptors are located in the cytoplasm
(especially aldosterone) and the nucleus ( estrogen and
progesterone).

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  In the nucleus , the receptor is called “ Nuclear
Hormone Receptor “ , it has 2 regions : (1) Hormone
Binding domain ,(2) DNA-binding domain.
 Then the (hormone-receptor complex) bind to a special
area on the DNA , that’s called Hormone Responsive
Element (HRE) , located adjacent to the gene that will
be transcribed.
 Wherever the receptor is the function is the same ,
Gene transcription  new protein formation .

WATER-SOLUBLE HORMONES
• Their receptors are in the membrane
• When they bind to it they may activate the G protein
system
• Activation of neighboring enzyme ; could be Adenylate
cyclase or guanylate cyclase , which convert ATP to
cAMP (2nd messenger)
• 2nd messenger (cAMP) activates a protein kinase which
phosphorylate proteins – thousands of proteins – this
what we call it a Cascade Reaction or Amplification
• The enzyme that’s responsible for the termination of
this process is called Phosphodiesterase by inactivating
the cAMP

MECHANISM OF THYRIOD HORMONE ACTION

• Thyroid is a lipid-soluble hormone
• T4 can be called a Growth hormone
• T4 is converted to T3 in the CELL’S CYTOPLASM by the
enzyme Iodinase , and T3 is the most active form
• Since it’s lipid-soluble it goes inside the cell, inside the
cell it binds to a ligand-binding domain, the other half-
site is vit. A derivative
• The the DNA-binding domain bind to the hormone
respond element (HRE) – as demonstrated below .
• Transcription of gene and formation of new proteins
• T4 and T3 increase the metabolic rate of the cell  that
means increasing the formation of Na+-K+ ATPase to

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 harvest enough energy for the enzyme activity
required to grow

Cell Membrane Phospholipid Second Messenger

System
• The peptide hormone bind to its receptor on the cell
membrane which activates G protein within the
membrane
• G protein stimulates Phospholipase C
• Phospholipase C breaks down the phospholipid of the
the membrane into Diacylglycerol (DAG) and form
Inositol-3-phosphate (IP3)
• IP3 goes to the endoplasmic reticulum (ER) and
stimulate the release of Ca++
• DAG stimulate the Protein Kinase C
• Which leads to the Phoshporylation of certain proteins
• Ca++ binds to Calmodulin and activate another kinase ;
it could be protein kinase B or Ca++- Calmodulin-
dependent protein kinase

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2nd messengers discussed so far :
1- cAMP , cGmp
2- Ca++ - Calmodulin
3- DAG (diacylglycerol)
4- IP3 (inositol-3-phosphate)
5- STAT

LEPTIN
• Produced in the Adipose Cells
• It INHIBITS the appetite
• So people with eating abnormalities might have
abnormal (LOW) levels of Leptin in their bodies

 LH , FSH , TSH and hCG are glycoproteins and water-

soluble hormones consist of 2 alpha subunits and 2 beta
subunits, the alpha subunits are common but the beta
subunits differ.

Determinants of Free Hormone Receptor Binding

 The relation between the free hormone and the
hormone receptor is reversible ; which means that he
hormone will dissociate from the receptor after
performing its function
 Carrier-bound hormones also have a reversible relation
with their receptors
 Carrier proteins could be globulin or albumin for steroids
, the importance of these carriers is the prolongation of
the hormones effect ; like thyroxin – its half-life is 7 days
 On the other hand water- soluble hormones’ half-life are
much less (the longest could reach hours)

• Hormone concentration is regulated by negative

feedback.
• There are some exceptions , some hormones are
regulated by positive feedback , such as progesterone
and estrogen .

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 Negative Feedback Positive Feedback

+ +

Endocrine Target Endocrine Target

cell cell cell cell
_ +

Biological effects Biological effects

I’m sorry for any inconvenience …..

a Wise Dude once said : “ take it easy , it’s not always

that HARD “ .

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