L9

Question 1

how do hormones signal?

Answer 1

1. hormone binds to receptor
2. changes the conformation and activity of the receptor
3. alters the activity of intracellular signaling pathways
4. leads to change in synthesis of target proteins and/or modification of existing target proteins

Question 2

6 characteristics shared by receptors

Answer 2

• large proteins
• families,
• can be multiple receptors for one ligand or more than one ligand for a receptor
• variable number in target cell (~500-100,000)
• can be activated and inhibited
• located in cell membrane, cytoplasm

Question 3

what does it mean for cellular receptors to be saturable?

Answer 3

A receptor has a limited number of binding sites, and is therefore saturated at high ligand concentrations.

Question 4

4 properties of receptors

Answer 4

• high affinity (very strong interaction)
• saturable
• specific
• reversible

Question 5

two types of cellular receptors

Answer 5

intracellular signal receptors
cell membrane receptors

Question 6

intracellular signal receptors

Answer 6

• lipophilic signal molecules diffuse through the cell membrane and bind to the receptor in the cytosol or nucleus
• binding to cytosolic or nuclear receptors triggers slower responses related to changes in gene activity

Question 7

cell membrane receptors

Answer 7

• extracellular signal molecule binds to a cell membrane receptor
• binding triggers rapid cellular responses

Question 8

what are the 4 types of plasma membrane receptors?

Answer 8

• G protein-coupled receptors
• receptor-enzyme receptors
• receptor-channel
• integrin receptor

Question 9

do peptide hormones interact with cell membrane or intracellular receptors?

Answer 9

• cannot penetrate target cell
• bind to surface receptors and activate intracellular processes through second messengers

Question 10

do steroid hormones interact with cell membrane or intracellular receptors?

Answer 10

• penetrate plasma membrane and bind to internal receptors (usually in nucleus)
• influence expression of genes of target cell
• take several hours to days to show effect due to lag for protein synthesis

Question 11

how do hormones bind to hormone response elements?

Answer 11

• bind to cytoplasmic receptors in cytoplasm or nuclear receptors in nucleus
• this forms a hormone-receptor complex, which binds to the hormone response element (HRE)

Question 12

hormone response elements

Answer 12

specific DNA sequences

Question 13

give an example of a hormone response element

Answer 13

estrogen response element in DNA

Question 14

how can receptors inhibit transcription?

Answer 14

by recruiting co-repressors

Question 15

how do receptors have specific effects?

Answer 15

only genes with the response elements will be activated/repressed

Question 16

structure of G protein-coupled receptors (GPCR)

Answer 16

• membrane-spanning proteins
• cytoplasmic tail linked to G protein, a three-part transducer molecule

Question 17

function of GPCRs

Answer 17

• G protein-coupled adenylyl cyclase-cAMP system is the signal transduction system for many protein hormones
• when G proteins are activated, they open ion channels in the membrane and alter enzyme activity on the cytoplasm side of the membrane

Question 18

what second messengers to G protein-coupled receptors use?

Answer 18

some lipid second messengers:
eg diacylglycerol (DAG) and inositol triphosphate (IP3)

Question 19

state three types of G proteins, including their target and activity

Answer 19

Gs
target: adenylyl cyclase
activity: stimulatory

Gq
target: phospholipase C
activity: stimulatory

Gi
target: adenylyl cyclase
activity: inhibitory

Question 20

describe Gs activity

Answer 20

1. signal molecule binds to G protein-coupled receptor (GPCR), which activates the Gs protein
2. Gs protein turns on adenylyl cyclase, an amplifier enzyme
3. adenylyl cyclase converts ATP to cyclic AMP
4. cAMP activates protein kinase A
5. protein kinase A phosphorylates other proteins, leading to a cellular response

Question 21

describe Gq activity

Answer 21

1. signal molecule activates receptor and associated G protein
2. G protein activates phospholipase C (PL-C), an amplifier enzyme
3. PL-C converts membrane phospholipids into diacylglycerol (DAG) which remains in the membrane and IP3, which diffuses into the cytoplasm
4. DAG activates protein kinase C (PK-C), which phosphorylates proteins
5. IP3 causes release of Ca2+ from organelles, creating a Ca2+ signal

Question 22

describe Gi activity

Answer 22

inhibits adenylyl cyclase, meaning ATP is not converted into cAMP

Question 23

give an example of a human use of G-protein coupled receptors

Answer 23

flight or flight responses are mediated by epinephrine, norepinephrine and G-protein coupled receptors:
liver - glucose release
fat - fatty acid release
heart - muscle contraction
skeletal muscle blood vessels - less vasoconstriction
intestine, skin, kidney: vasoconstriction

Question 24

explain and detail how epinephrine can bind to different isoforms of the adrenergic receptor

Answer 24

epinephrine + α-receptor response: causes vessel to constrict

epinephrine + β2-receptor response: causes vessel to dilate

Question 25

similarities/differences between epinephrine and norepinephrine

Answer 25

- both result in protein phosphorylation which leads to target cell response - have diverse physiological effects via different receptors and effectors

Question 26

list the 3 G-protein subunits that GPCR sits with in an inactive state

Answer 26

alpha, beta, gamma

Question 27

the alpha subunit of G protein has multiple isoforms:

Answer 27

Gas, Gai, Gaq

Question 28

3 flow charts for the different isoforms

Answer 28

Gas -> adenylyl cyclase -> cAMP -> PKA -> cell response Gai -> (-)adenylyl cyclase -> cAMP Gaq -> PLC -> (a) DAG -> PKC (b) IP3 -> Ca2+ -> cellular response

Question 29

what are the different ways in which signaling can be modulated?

Answer 29

- hormone degraded - receptor down-regulation or up-regulation - receptor desensitisation towards hormone - breakdown of second messengers - modification of any component in the pathway - biological effect provides feedback to reduce hormone secretion

Question 30

describe the process of endocytosis, exocytosis, and membrane recycling in cells

Answer 30

1. ligand binds to membrane receptor 2. receptor-ligand migrates to clathrin-coated pit 3. endocytosis 4. vesicle loses Cathrin coat, which returns to membrane 5. receptors and ligands separate 6. ligands go to lysosomes or Golgi for processing 7. transport vesicle with receptors moves to the cell membrane 8. transport vesicle and cell membrane fuse (membrane recycling) 9. exocytosis