Chapter 5: Control of cells by chemical messengers

Question 1

Intracellular Chemical messengers

Answer 1

• include hormones and neurotransmitters
• require chemical messenger binds to specific receptors on target cells and requires signal transduction proceeds, sequence of intracellular events in response to chemical messengers

Question 2

Receptor composition

Answer 2

• proteins and glycoproteins

Question 3

receptor locations

Answer 3

• plasma membrane (interact with water-soluble/transmembrane chem messengers)
• nucleus (interact with lipid-soluble chem messengers)

Question 4

receptor specificty

Answer 4

• only specific receptors will bind particular chemical messengers
• mostly bind with only 1 chemical messenger
• different cell types possess receptors for particular messengers (ligands)
• different cell types may have receptors for the same chemical messenger
• a single cell type may contain more than one receptor type for a single messenger

Question 5

receptor affinity

Answer 5

• can have different affinity for different chemical messengers

Question 6

receptor saturation

Answer 6

• may be saturated via chemical messengers

Question 7

receptor competition

Answer 7

• antagonists and agonists

Question 8

antagonist

Answer 8

• binds to a receptor
• does NOT trigger cell’s response
• blocks the receptor from binding to its proper chemical messenger
• example: beta blocker

Question 9

agonist

Answer 9

• binds to receptor
• triggers the cell’s response
• mimics the messengers response

Question 10

Down regulation

Answer 10

• decrease in total number of target cells receptors for a given messenger
• response to chronic high extracellular messenger concentration

Question 11

Up regulation

Answer 11

• increase in total number of target-cell receptors for a given messenger
• response to chronically low extracellular messenger concentration
• supersensitivity

Question 12

mechanisms in which up/down regulation occurr

Answer 12

• receptor synthesis or degredation

- alterations in gene expression –> code for receptors

Question 13

signal transduction pathways

Answer 13

• sequence of events leading to ultimate cellular response

- initiated by receptor activation

Question 14

receptor activation

Answer 14

• change in the conformation of the receptor induced by binding of chemical messenger

Question 15

types of cellular responses

Answer 15

• changes in the permeability, transport properties, or electrical state of the cell’s plasma membrane
• changes in the cell’s metabolism
• changes in the cell’s secretory activity
• changes in the cell’s rate of proliferation or differentiation
• changes in contractile activity

Question 16

signal transduction pathways initiated via lipid-soluble messengers

Answer 16

• steroid hormones, thryoid hormones, 1,25-dihydroxy vitamin D
• involve intracellular receptors most located in nucleus (in cytoplasm too, but rare)
• activation alters rates of gene transcription

Question 17

signal transduction pathways initiated via water-soluble messengers

Answer 17

• most hormones, neurotransmitters, and paracrine/autocrine compounds
• receptors are located in the plasma membrane
• 4 types of receptors:
  1) receptors are ligand-gated channels
  2) receptors are ions
  3) receptors are bound to and activate JAK kinases
  4) G-protein-coupled receptors

Question 18

first-messenger

Answer 18

the intracellular chemical messenger that binds to the plasma membrane receptor (hormone or neurotransmitter)

Question 19

second-messenger

Answer 19

• a substance that enters or is generated in the cytoplasm in response to receptor activation by the first messenger; serves as a chemical relay to the interior of the cell

Question 20

receptors that are ligand-gated ion channels

Answer 20

• receptor activation by a first-messenger –> conformational change in the receptor –> opens the channel through the plasma membrane
• increased diffusion of one or more types of ions across the plasma membrane (change in the mem potential)
• increased cytosolic calcium concentration is important in many signal transduction pathways

Question 21

Receptors that function as enzymes

Answer 21

• majority are receptor tyrosine kinases!

Question 22

Mechanism of action of receptors function as enzymes

Answer 22

• receptor activation
• conformational change
• activation of enzymatic portion of the receptor
• autophosphorylation
• formation of phosphotyrosines
• phosphotyrosines serve as docking sites for cyotoplasmic proteins (docking proteins)
• bound docking proteins bind and activate other proteins, which activates one or more signaling patways
• cellular response (usually an effect on cell proliferation or differentiation)

Question 23

exception with receptors as enzymes

Answer 23

• receptor acts as a guanylyl cyclase
• catalyzes formation of cyclic GMP (cGMP) in the cytoplasm
• cGMP acts as a second messenger, activates cGMP-dependent protein kinases that phosphorylates proteins involved in the transduction pathway (cells response)
• found in large amounts in the retina; involved in processing visual inputs

Question 24

Receptors that interact with cytoplasm JAK kinases

Answer 24

• receptor is associated with cytoplasmic JAK kinase (tyrosine kinase) –> function as a unit

Question 25

mechanism of action of receptor with cytoplasm JAK kinase

Answer 25

- binding of first messenger - conformational change in receptor - activates JAK kinase - JAK kinase phosphorylates a protein or proteins (many act as transcription factors) - synthesis of new proteins that mediate cell's response

Question 26

G-protein-coupled receptors

Answer 26

- largest category | - g-protein complex located on the cytoplasmic surface of the plasma membrane is bound to receptor

Question 27

mechanism of action of g-protein-coupled receptors

Answer 27

- binding of a first messenger to receptor activates it - change in receptor conformation - increased affinity of alpha subunit of g protein for GTP - GTP binds to alpha subunit - dissociation of the alpha subunit from g-protein complex - alpha subunit links to another plasma membrane protein (plasma membrane effector protein)

Question 28

Gs vs Gi proteins

Answer 28

- Gs: activate adentltl cyclase --> cAMP production | - Gi : inhibit adentltl cyclase activity --> decrease cAMP production

Question 29

phospholipase c, diacylglycerol, and inositol triphosphase mechanism of action

Answer 29

- receptor activation by 1st messenger - activation of Gq - activation of phospholipase C - catalyses breakdown of PIP2 into diacyglyerol and inositol triphoshate which become second messengers in cell - diacyglycerol activates protein kinase C enzymes that phosphorylate other proteins --> cells response - IP3 binds to receptors (ligan gated Ca++ channels) on endoplasmic reticulum which open channels and calcium diffuses out of ER into the cytoplasm --> biochem events --> cells respons

Question 30

control of ion channels by G proteins

Answer 30

- direct gprotein gating | - indirect gprotein gating

Question 31

calcium as second messenger

Answer 31

- plasma membrane Ca++ channels can be ligand-gated or voltage-gated - calcium acts as second messenger by binding to various cytosolic proteins and altering their conformation

Question 32

cyclooxygenase inhibitors

Answer 32

- asprin and nonsteroidal anti-inflamm drugs - inhibit production prostoglandins and thromboxates - steroids inhibit phospholipase A2

Question 33

Eicosanoids

Answer 33

- stimulate inflammation and in immune response - drugs act to inhibit production of eicosanoids by inhibiting cyclooxygenase or phospholipase A2 - generated by poly-unsaturated acid which is part of membrane phospholipids - first messenger binds to receptor activating phospholipase A2 - A2 splits off arachondonic acid from membrane phospholipids - arachodonic acid is metabolized in 2 ways

Question 34

arachodonic acid metabolized

Answer 34

1) acted on by enzyme lipo-oxygenase --> lucotryannes | 2) acted on by enzyme cyclo-oxygenase --> cyclic endoproxide--> either prostaglandin or thromboxates

Question 35

receptor activation ceases in signal transduction pathways

Answer 35

- decrease in amount of first messengers - receptor inactivation - -> chemically alteres (phosphorylated)...lower its affinity for the first messenger or prevent G-protein binding - internalized by endocytosis