Ch 16 Textbook Material Pt2 (G-protein-coupled receptors)

What enzyme mediates most of cAMP’s effects in cells?

cyclic-AMP-dependent protein kinase (PKA)

What activates PKA?

the binding of cAMP to its regulatory protein, causing a conformational change that releases the active kinase

What does activated PKA do?

it phosphorylates specific serine or threonine residues on target proteins

How does PKA activation alter cellular activity?

by changing the function of target proteins through phosphorylation

cAMP activates

protein kinase A

G-protein activates

adenylyl cyclase

GPCR activates

G-protein

PKA activates

glycogen phosphorylase through multiple steps

• results in glycogen breakdown

PKA represses

glycogen synthase

• prevents glucose conversion into glycogen

What enzyme-mediated signaling pathway can GPCRs activate besides adenylyl cyclase?

the phospholipase C pathway

What does phospholipase C do once activated?

cleaves an inositol phospholipid in the plasma membrane to generate two second messengers

What is the name of the signaling pathway that begins with activation of phospholipase C?

inositol phospholipid pathway

Where is the inositol phospholipid found in the membrane?

in the cytosolic leaflet of the plasma membrane lipid bilayer

What two second messengers are produced by phospholipase C cleavage?

• inositol 1,4,5-triphosphate (IP3)

• diacylglycerol (DAG)

What is IP₃?

a water-soluble sugar phosphate that diffuses into the cytosol

What does IP₃ do?

binds to and opens Ca2+ channels in the ER membrane

What happens when IP₃ opens ER Ca²⁺ channels?

Ca2+ stored in the ER is released into the cytosol

• increases cytosolic Ca2+ concentration

What is diacylglycerol (DAG)?

a lipid that remains in the plasma membrane after cleavage by phospholipase C

What role does DAG play in signaling?

helps recruit and activate protein kinase C (PKC)

What is required to activate PKC?

• DAG (in the membrane)

• Ca2+

What does activated PKC do?

phosphorylates specific intracellular proteins

Why is Ca²⁺ such an important intracellular messenger?

because it controls many key cellular processes in response to various stimuli across nearly all eukaryotic cells

What happens when a sperm fertilizes an egg cell?

Ca2+ channels open, and the rise in cytosolic Ca2+ triggers the egg to begin development

How does Ca²⁺ stimulate cellular responses?

by binding to and influencing the activity of various Ca2+-responsive proteins

What is the most common and widespread Ca²⁺-responsive protein?

calmodulin

What happens when Ca²⁺ binds to calmodulin?

calmodulin changes shape, enabling it to bind and regulate many target proteins

What makes nitric oxide (NO) different from most second messengers?

it is small and hydrophobic enough to diffuse across membranes and affect nearby cells

What type of molecule is nitric oxide (NO)?

a gas that acts as a signaling molecule in many tissues

What type of cells release NO in response to acetylcholine?

endothelial cells

What triggers endothelial cells to produce NO?

acetylcholine binds to and GPCRs on their surface, activating Gq and causing Ca2+ release inside the cell

After being produced, where does NO diffuse?

into smooth muscle cells in the walls of nearby blood vessels

What enzyme does NO activate inside target cells?

guanylyl cyclase

What reaction does guanylyl cyclase catalyze?

the conversion of GTP into cGMP

What role does cyclic GMP play in NO signaling?

it acts as a second messenger to mediate the effects of NO, such as smooth muscle relaxation

What GPCR detects light in rod photoreceptor cells?

rhodopsin

What G protein is activated by rhodopsin?

transducin

What mechanism enables this light adaptation?

negative feedback

• an intense response lowers cytosolic Ca2+, which inhibits the enzymes responsible for amplification

Rhodopsin molecules respond to light AND

activate G proteins which activate cGMP phosphodiesterase which cleaves cGMP