USMLE Step 1 – Receptors

Tyler York

This video describes the types of receptors and their mechanism of action. Many hormones, cytokines and drugs bind to these receptors to produce various effects. Important among them is Insulin which uses a tyrosine kinase receptor. The sample USMLE question at the end of the video will help to understand application of the concept.

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Full USMLE Step 1 – Receptors video transcript:

Hi, this is Sujatha. In today's video we will cover receptors. Receptors are molecules to which various drugs, hormones, cytokines, etc. Will bind to produce their effect. There are five types of receptors.
These are catalytic receptors, nuclear receptors, inotropic receptors, G protein couple receptors, also known as GPCR and soluble receptors. Catalytic receptors are membrane bound enzymes whose activity is changed by the binding of the ligand. They have a ligand binding site and a catalytic site, insulin.
Prolactin tumor across this factor are the major molecules that use catalytic receptors for their action. Let us look at the insulin receptor. The insulin receptor has inherent tyrosine kinase activity Binding of the ligand which is insulin causes auto phosphorylation of tyrosine residues in the tail of the receptor which then activates various metabolic pathways like jakstat pathway, Bi 3 kinase pathway, etc.
Which in turn affect cell growth, metabolism and oncogenesis, etc. Nuclear receptors, some of their ligands bind directly to the nuclear receptor, while other ligands first bind to a cytoplasmic receptor before translocating with the receptor into the nucleus. The nuclear receptors include vitamins AD.
Retinoids, thyroid hormone and the female hormones estrogen and progesterone. Testosterone, glucocorticoids and mineralocorticoids will bind first to a cytoplasmic receptor before translocating and binding to the nuclear receptor. All nuclear receptors will have DNA binding domains which have zinc, finger motifs, GPCR or G protein coupled receptors. These receptors are located on the cell membrane.
And they consist of seven trans membrane spanning regions. These receptors are called GPCR because they are associated with a heterotrimeric G protein. The G protein consists of three different molecules, G alpha, G beta and G gamma. In its inactive state, the G alpha is bound to GDP.
Ligand binding causes a conformational change which results in the dissociation of G alpha from the GDP and then it associates with GTP. G proteins have inherent Gtpa's activity. There are three types of G alpha proteins, GI, GS and GQ. Of these GS and GQ, they will stimulate downstream enzymes.
Whereas GI will inhibit downstream enzymes, different G proteins will activate different enzymes which in turn will produce different second messengers which in turn will activate serine and threonine kinases to produce their effect. The table shows the different types of G alpha proteins, the enzymes and 2nd messengers that are produced in their metabolism.
GS is going to stimulate the enzyme adenylate cyclase and the second messenger is camp whose levels will be increased in the cell. GQ is going to stimulate phospholipase C to produce the 2nd messengers IP3 and DAG. GI on the other hand is going to inhibit adenylate cyclase as a result of which the levels of camp is going to be decreased.
Inotropic receptors. These are membrane bound ligand gated ion channels. Binding of the ligand changes the flow of ions through these ion channels. Examples are receptors for GABA, A, glycine, nicotinic receptors, etc. Soluble receptors. These receptors exist in two forms, one form is membrane bound and the other is a soluble form.
The soluble form is nothing but the extracellular portion of the membrane bound receptor. Interleukins, interferons, thrombopoietin, growth hormone, TNF, alpha, etcetera are some of the major molecules that can bind to soluble receptor. When the ligand binds to the soluble receptor, it prevents the ligand from binding to the cell membrane receptor, hence it blocks its action.
This mechanism can be used to our advantage in therapeutic purposes. For example, it intercept is a decoy soluble receptor for TNF alpha. So when you administer it intercept to a patient, it is going to bind to TNF alpha. Hence it prevents the action of TNF alpha which can be very useful to treat patients who are suffering from conditions like psoriasis, rheumatoid arthritis etcetera.
Let us look at a typically US simile questions on this topic. Most questions are related to the mechanism of action of receptors and also specifically to G protein couple receptors. I will give you a second to look at the question first. The question describes the patient.
Who had a recent history of severe head trauma and is now suffering from what looks like diabetes insipidus. You have ruled out diabetes mellitus because he has a normal blood glucose but depending on the clinical features looking like diabetes and also.
A decreased osmolality in the urine while at the same time increased osmolality in the blood and his response to desmopressin. You are sure that he is suffering from diabetes insipidus. So the beneficial effect of desmopressin in this case.
Is because of its action on its V2 receptor. The V2 receptor of desmopressin is an example of a G protein couple receptor and the type of G alpha in V2 receptor is GS that stimulates adenylate cyclase and which will result in increase of camp. So you can also make other correlation which is also often asked in the usmile.
Is that a patient who has diabetes insipidus will have increased urinary levels of camp and now you know why that happens. Hope this video helped you understand receptors in general and G protein couple receptors. Thanks for watching.
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