Topic 2

Question 1

How do G-protein coupled receptors activate

Answer 1

• All G-proteins active when bound to GTP and inactive when bound to GDP

Question 2

What are G-Protein coupled receptors

Answer 2

• Single largest category of receptor type in animal cells
• Receptors that act by coupling with G protein
• Acts indirectly on enzymes or ion channels in plasma membrane with aid of G protein
• Has 7 transmembrane domains that anchor the receptor in the plasma membrane
• 800 genes in human encodes for GPCR, half encode for odorant receptors involved in taste and smell

Question 3

How are GPCR activated

Answer 3

• All GPCRs are active when bound to GTP and inactive when bound to GDP
• G protein will bind with GTP when ligand binds with receptor, hence G protein activated
• Activated G protein activated effector protein, providing link between receptor and effector proteins that produce cellular responses
• Effector protein may act directly on cellular proteins or produce a second messenger to cause a cellular response
• Made up of three subunits, alpha, beta and gamma, also called as heterotrimeric G proteins
• Upon binding of ligand on its associated receptor, G protein exchanges GDP for GTP and dissociates into 2 parts consisting of G alpha subunit bound to GTP and G beta gamma subunit
• Signal can be propagated by either G alpha or G beta gamma subunit
• The hydrolysis of bound GTP to GDP by
  G alpha causes reassociation of the heterotrimer and restores the off state, inactivating the system

Question 4

what are effector proteins?

Answer 4

usually enzymes which may…

1. phosphorylation proteins to directly propagate the signal
2. produce a second messenger to initiate a signal transduction pathway

Question 5

what are the two common effector proteins that produce second messenger

Answer 5

1. Adenylyl Cyclase (Second messenger: Cyclic AMP)
2. Phospholipase C (Second messenger: IP3 and DAG)

Question 6

how are second messengers produced

Answer 6

• second messengers are signaling molecules produced within cell
• nucleotide ATP is converted by enzyme adenylyl cyclase into cyclic AMP or cAMP and pyrophosphate (PPi)

Question 7

cAMP signaling pathway

Answer 7

• Ligand binds to GPCR, activating a G protein
• G protein then activates effector protein adenylyl cyclase , which
  catalyses conversion of ATP to cAMP
• The cAMP then activates Protein Kinase A (PKA)
• Which then phosphorylates target proteins to produce a cellular response

Question 8

What is a glucagon receptor

Answer 8

• A type of G protein coupled receptor
• Glucagon is a hormone that stimulates liver cells to mobilize glucose
• upon binding of the receptor on liver cells, by glucagon, the associated G protein is activated, exchanging GDP for GTP
• active G protein complex dissociates into 2 sub units, G alpha and G beta gamma
• the G alpha subunit (bound to GTP) acts on adenylyl cyclase (effector protein) to produce cyclic AMP (second messenger)

-production of cAMP results in activation of PKA

• Activation of PKA results in the activation of another protein kinase called phosphorylase kinase
• activated phosphorylase kinase in turn activates glycogen phosphorylase
• activated glycogen phosphorylase cleaves off units of glucose-6-phosphate from their glycogen polymer
• increases blood glucose level

Question 9

what are the subsequent actions that take place as the glucagon receptor is activated?

Answer 9

• PKA also inhibits the enzyme glucogen synthase, inhibiting the enzyme, thus preventing the synthesis of glycogen
• PKA also phosphorylates other proteins that activate the expression of genes that are used to encode the enzymes for synthesizing glucose

(All these events help in the increase of blood glucose level)

Question 10

what are steroid hormone receptors?

Answer 10

• Intracellular receptor present in the cytoplasm
• ligands are steroid hormones: cortisol, oestrogen, progesterone, testosterone
• steroid hormones are non-polar and can readily diffuse across the plasma membrane

Question 11

what are the three functional domains in a steroid receptor

Answer 11

• A hormone binding domain
• DNA binding
  domain
• A domain that can interact with coactivators to affect the level of gene transcription (inhibitor)

Question 12

how are steroid hormone receptors activated?

Answer 12

• Steroid hormone receptors are inactive before the binding of hormones and thus cannot bind to DNA
• Upon binding of hormone, the inhibitor will be released from the DNA binding domain
• formation of hormone- receptor complex leads to a shift from the cytoplasm to into the nucleus
• In the nucleus the DNA binding domain binds to specific nucleotide sequences on DNA, at sites near the gene they regulate
• the primary function (cellular response) is regulation of gene expression

Question 13

what are Nitric oxide receptors

Answer 13

• A type of intracellular receptor
• A receptor that acts as an enzyme: Guanylyl cyclase
• Nitric oxide , a small gas molecule, is able to diffuse readily into the cell
• Nitric oxide binds to and activated guanylyl cyclase, leading to the production of cyclic guanosine mono phosphate (cGMP)
• the effect is to cause relaxation of smooth muscle cells, resulting in dilation of blood vessels and increased blood flow

Question 14

what are the two medicines related to the function of NO receptor?

Answer 14

Nitroglycerin and Viagra

Question 15

what is Nitroglycerin ?

Answer 15

• drug used to treat angina
• converted by cells to NO to help with the relaxation of blood vessels, relieving the symptoms of angina
• NO serves as a ligand for the NO receptor

Question 16

what is Viagra?

Answer 16

-Viagra works by inhibiting the enzyme cGMP phosphodiesterase which causes the breakdown of cGMP

• thus cGMP remains high in the cells and allows the relaxation of smooth muscle cells in erectile tissues, increasing blood flow
• viagra does not bind into any intracellular receptors, but it does help in maintaining the effect produced by an activated NO receptor (dilation of blood vessels)