biochem L7R signaling Flashcards
Differentiate among contact, paracrine, autocrine and endocrine signaling.
Contact signaling-signaling through cell-cell contact .
Paracrine signaling– short distance signaling between different cells.
Autocrine signaling– short distance signaling involving the same
(or same type of) cell(s).
Endocrine signaling– long distance signaling between endocrine
glands and target cells.
Explain the general steps of signaling and their defects through the example of the neuromuscular junction signaling.
Chemical Signal : Acetylcholine
signal detection (receptors):
- nicotinic ACh receptor (skeletal muscle) Na+/K+channel
- muscarinic ACh receptor (heart muscle)G protein-linked receptor
Conversion of signal:
- nicotinicAChreceptor lets Na+in and K+out
- muscarinicAChreceptor regulates a K+channel
Regulation:
1.acetylcholine esterase degrades excess ACh
Diseases
Myasthenia gravis: autoimmune neuromuscular disease ( muscle weakness,muscle fatigue)
Own words: antibodies attack against its own nicotinic ACh receptors causing endocytosis of those receptors, inhibit ACh binding to receptors ( insufficent signaling)
Management: (increase signaling)
see Picture***
Medications :pyridostigmine, neostigmine,physostigmine, all reversible ( competitive inhibitors)
Too much signaling: Exposure to pesticides/insecticides —-> Irreversibly inhibit acetylcholine esterase—–> Excess ACh is not destroyed—-> Contraction-relaxation cycle of muscle is impaired (especially dangerous in heart)=death
Managment: decrease signaling
Altropine (muscarinic AChreceptor antagonist): blocks ACh Receptors, inhibit ACh signaling
List the 5 major groups of chemical signals and their roles in the human body.
Neurotransmitters– produced by the nervous system
Ex. ACh
Hormones– produced by the endocrine system (mostly)
Cytokines– produced by the immune system, regulate immune function
Eicosanoids– produced in response to injury or inflammation
Growth factors– regulate cell differentiation and proliferation
* most are Water Soluble meaning can diffuse from one cell to another.
*some are water insoluble Steriod hormones, thyroid hormone, Vitamin D3 need speacial transporters)
Predict the type of receptors that bind ligands based on the ligands’ chemical nature.
Associate physiologically important chemical signals with their receptors
Type I nuclear receptor signaling ( Steroid hormones)
- Cortisol
- Aldosterone
- Progesterone
- Testosterone
Type III nuclear receptor signaling (steroid hormones)
- Estradiol
Type II nuclear receptor signaling
- retinoic acid
- vitamin D3
- thyroid hormone
- fatty acids
Differentiate among the signaling mechanisms of type I/III, type II and nitric oxide intracellular receptors.
TYPE I AND III
- type I and III receptors are localized in the cytosol in complex with heat shock proteins (hsp)
- when the steroid hormone binds to the receptor, the hsp is shed and the receptors are dimerized
- The dimerized receptor-hormone complexes translocate from the cytosol into the nucleus.
- In the nucleus the receptor-hormone complexes bind to the DNA(to a hormone-responsive element) and with the help of coactivators induce gene transcription (the receptors are transcription factors).
*Dexamethasone, an anti-inflammatorysteroid drug acts through this signaling pathway. It is ~ 30 times more efficient than the naturally occurring steroid hormone, cortisol.
Differentiate among the signaling mechanisms of the 3 main types of cell surface receptors.
3 main cell surface receptors:
Ion channel – linked receptors-Chemical signal into an electrical signal.
ex. Nicotinic ACh receptor
G-protein linked receptors-chemical signal induces activation of G-protein and it has a snowball effect in the cell.
- Adrenergic( epinephrine )Beta-blockers used to slow down heart rate for those with Cardiac Arrhythmias.
- Glucagon receptors : controls metabolic effect during fasting
- Muscarinic acetylcholine receptor: regulates heart rate
-Rhodopsin: senses light in the Rods and cons
-Dopamine: ( neurotransmitter) receptor, Targets this area in those that have Schizophrenia, Parkinson’s disease, attention deficit disorder.
Enzyme or enzyme-linked receptors: chemical signal to the receptor activates enzymes, intracellular signaling cascade and changes the behavior of the cell.
* dont need secondary messengers becuase already have kinases on receptors. G-Linked need kinase.
Explain the main concepts of second messengers and kinases in signal transduction pathways.
- the first messenger is the hormone that connects to receptor on the surface once that happens the G proteins is activated Secondary messengers ( Cyclic AMP, Cyclic GMP, Ca 2+, Diacylglycerol, Inositrol Triphosphate)
- Intracellular signals activates kinases ( special enzymes that add phosphate groups to proteins – post-translational modification).
- Phosphorylation can activate or deactivate proteins
- Kinases is controled by Phosphatases ( remove phosphate groups from protiens)
- ATP is required to add phosphate group.
Differentiate among the 3 basic pathways of trimeric G-protein signaling (adenylyl cyclase, protein kinase C and ion channel modulation).
One of the G protien signaling are
- Adenylyl cyclase regulation ( ATP-cAMP)
PROCESS: hormone binds to receptor located in the plasma membrane, (which is connected to alpha,beta, gama with a GDP.) g-protien exchanges GDP -> GTP which makes alpha split form Beta Gamma subunits separate. The alpha activates adenylyl cyclase. which makes ATP
( GsA) Induces cell response.
GiA inhibits the effect of Adenylyl cyclase.
2.Protien Kinase C:
Not sure if you want C OR A
- ION CHANNEL MODULATION:
In the ion channels one example is the muscarinic ACh receptors
(Gbeta gamma) activates the ion channel letting k+ our into the extracellular space. no 2nd messenger needed or kinases.
Differentiate between the mechanisms of abnormal G protein signaling caused by cholera and pertussis toxins.
Cholera Toxin: Transfers an ADP-Ribose group to GsAlpha ( by post-translational modification) making the GTP stay on with GsAlpha making tons of cAMP.
*causes extreme salt and water efflux( get out ) from gut epithelial cells to the lumen, causing diarrhea.
Pertusis Toxin: ( whooping cough) ADP-ribose group to inhibitor GiAlpha (posttranslational modification). Adenylyl cyclase cannot be stoped l_ots of_ cAMP, increased mucus secretion in airway epithelium.
Distinguish among the 3 receptor/ receptor associated kinase signaling pathways (JAK/STAT, serine-threonine kinase, tyrosine kinase).
