G Proteins & Enzyme Linked Receptors

Metabotropic Receptors

Receptors associated with G proteins and secondary messenger systems

GPCR

G-protein coupled receptor

What are the effects of activating a G protein?

Activates an ion channel
Activates a second messenger (eg Ca)

Examples of G-protein activated enzymes

Adenylyl Cyclase
Guanylyl Cyclase
Phospholipase C

What products are produced in reactions involving these G-protein activated enzymes?

- adenylyl cyclase

- guanylyl cyclase

- phospholipase C

ATP -> cAMP

GTP -> cGMP

PIP2 -> DAG/IP3

What is the effect of Protein Kinase A/Protein Kinase G on cAMP/cGMP?

Phosphorylates them to cause the response

What is the effect of Phosphodiesterase on cAMP/cGMP?

Dephosphorylates them to form AMP/GMP

How do GPCR's work?

Ligand binds to GPCR
GDP attached to alpha subunit swaps for GTP
GTP detaches the alpha unit from beta and gamma units
This activates the cell response

What are the two mechanisms of turning proteins on?

- GTP binding to G proteins
- Phosphorylation

How does Noradrenaline cause bronchodilation?

NA binds to beta receptor
G protein activation
Activates cAMP
Inhibits MLCK
Causes bronchodilation

What are the affects of

- alpha adrenoreceptors?

- beta 1 adrenoreceptors?

- beta 2 adrenoreceptors?

increased BP and bronchoconstriction

increased HR

bronchodilation

Noradrenaline Structural Activity Relationship (SAR)

Increasing -OH groups on noradrenaline increases its potency

How do receptor tyrosine kinases work?

2 receptors stuck together
Causes 2 monomers to stick together and to phosphorylate tyrosine kinase
Causes cellular response