Chapter Three Text Molecular Basis Of Hormone Action

Question 0

What does the binding of a receptor induce

Answer 0

A conformational change in the receptor that initiates downstream signaling

Question 1

What determines the scope of hormone action

Answer 1

Tissue distribution of receptor

Question 2

How does downstream signaling differ

Answer 2

It differs across cell types to produce potentially diverse hormonal effects

Question 3

How is control of hormone receptors exerted

Answer 3

Through the constant synthesis, degradation and localization of hormone receptors

Question 4

What are the two hormone receptor super families?

Answer 4

Water soluble hormones and lipid soluble hormones

Question 5

Characteristics of water soluble hormones (4)

Answer 5

Plasma membrane is impenetrable
Cell-surface receptors transducer signal thorough membrane
Activate intracellular signaling pathways
Fast responses (seconds) as well as slow ones

Question 6

Characteristics of lipid soluble hormones (4)

Answer 6

Pass through plasma membrane
Receptors function as transcription factors in the nucleus
Activate or repress gene expression
Tend to be slow responses (hours-days)

Question 7

Three binding characteristics of binding receptors

Answer 7

High affinity
Reversible binding
Specificity

Question 8

How is signal transducer for cell-surface receptor

Answer 8

When hormone binds to receptor, the cascade of cytoplasmic responses is mediated through protein phosphorylation by kinase enzymes or the generation of second messengers via coupling to G proteins

Question 9

Two major groups of cell-surface receptors

Answer 9

Tyrosine kinase receptors and G-protein coupled receptors

Question 10

Tyrosine kinase receptors

Answer 10

Signal via phosphorylation of the amino acid, tyrosine

Question 11

Go-protein-coupled receptors

Answer 11

Activate or inhibit adenylate Cyclase and/or phospho lipase C (PLC)
Signal via second messenger: cyclic adenosine monophosphate (cAMP), inositol triphosphate (IP3), diacylglycerol (DAG) and intracellular calcium
Signal via phosphorylation of serine and threonine amino acids

Question 12

How does protein phosphorylation happen

Answer 12

Phosphate group is donated from ATP during catalysis by the kinase enzyme. It is accepted by the polar hydroxyl group of serine, threonine, or tyrosine and causes a conformational change in the 3D shape of the protein

Question 13

Two ways through phosphorylation of TK receptors can occur

Answer 13

Intrinsic TK activity located in the Cytosolic domain of the receptor
Separate TKs recruited after receptor activation

Question 14

How do intrinsic TK receptors phosphorylate

Answer 14

They auto phosphorylate upon binding of the appropriate hormone

Question 15

Which amino acids can be phosphorylated

Answer 15

Serine, threonine and tyrosine

Question 16

How do G protein coupled receptors work

Answer 16

Couple to G proteins at the inner surface of the cell membrane, leading to the generation of intracellular second messengers such as adenosine-3’, 5’-cAMP, diacylglycerol (DAG), and IP3. G protein receptors also exist for glutamate, thrombin, odorants, and the visual transduction of light.

Question 17

What does G protein coupled receptor signaling involve

Answer 17

Hydrolysis of GTP to GDP . G peoteins exist in the cell membrane as heterotrimeric complexes with alpha, beta and gamma subunits. Beta and gamma subunits have such affinity that functional units are Galoha and Gbeta/gamma. Hormone binding results in conformational change in alpha subunit, leading to an exchange of GDP for GTP.

Question 18

How do second messenger pathways work?

Answer 18

Activation of membrane bound adenylate Cyclase catalyzes the conversion of ATP to cAMP. cAMP interacts with protein kinase Aro unmask its catalytic site, which phosphorylates serine and threonine residues on a transcription factor called cAMP response element binding protein.

Question 19

What does CREB do on e it has been phosphorylated?

Answer 19

Translocation to the nucleus where it bonds to a short palindromic sequence in the regulatory regions of cAMP-regulated genes

Question 20

How is cAMP response terminated?

Answer 20

By a large family of phosphodiester ashes, including phosphorylation by PKA in a negative feedback loop. cAMP is hydrolyzed to inactive 5’-AMP

Question 21

Which hormones recruit G protein complexes with the Gqalpha subunit

Answer 21

TRH, GnRH, oxytocin

Question 22

What does Gqalpha subunit activate

Answer 22

Membrane-associated PLC, which catalyzes the conversion of PI 4,5-bi phosphate (PIP2) to DAG and IP3.

Question 23

What does IP3 do?

Answer 23

Stimulates thr transient release of calcium from the ER to activate several calcium-sensitive enzymes, including isoforms of protein kinase C and proteins like calmodulin. The calcium ions also activate Cytosolic guanylate Cyclase, which catalyzes the formation of cyclic guanosine monophosphate (cGMP).

Question 24

What is the target of DGA signaling

Answer 24

PKC, which activates phospho lipase A2 to liberate arachnid oriC acid from phospholipids and generate potent eicosanoids, including thromboxanes, leucotrienes, lipoxons and prostaglandins.

Question 25

What happens when ligands bind to nuclear receptors

Answer 25

The receptors bind DNA and function as transcription factors. Biological responses of nuclear receptors are slow.

Question 26

Orphan nuclear receptors

Answer 26

Have no endogenous ligand

Question 27

Why do ligands for nuclear receptors undergo enzymatic modification within the target cell

Answer 27

To convert circulating hormone into a more or less potent metabolite prior to receptor binding.

Question 28

What do unbound steroid hormone receptors associate with in their resting state

Answer 28

Heat-shock proteins

Question 29

What do heat shock proteins do to steroid hormone binding receptors

Answer 29

They obscure the DNA binding domain so that they are considered incapable of bonding the genome.

Question 30

What happens to heat shock proteins when a steroid binds

Answer 30

Conformational change causes their dissociation

Question 31

What ahopens when heat shock peoteins dissociate from receptors

Answer 31

Two polypeptide loops are revealed that are stabilized by zinc fingers. Once two steroid receptors have dimerized, the motifs bind to target DNA at the specific hormone response element (HRE).

Question 32

Where is thyroid hormone receptor located

Answer 32

In the nucleus bound to DNA at the thyroid hormone response element

Question 33

What happens to unliganded thyroid hormone receptor in the absence of hormone

Answer 33

TR dimerized with the retinoid X receptor and tends to recruit nuclear proteins that inhibit transcription.

Question 34

What happens when thyroid hormone binds to receptor

Answer 34

Nuclear proteins and retinoid X receptor dissociate, and TR recruits transcriptional co-activators. A sequence of events recruit DNA-dependent RNA polymerase, which leads to transcription.

Question 35

Variant nuclear receptors

Answer 35

Have atypical DNA binding domains and potentially function via indirect interaction with genome

Question 36

Pituitary-specific transcription factor 1 regulates what

Answer 36

The expression of genes encoding GH, PRL, and the beta subunits of TSH. PIT1 mutations show reduced or absent levels of these hormones, causing short stature, and are at risk of congenital secondary hypothyroidism with severe learning disability

Question 37

What transcription factors does the development of the pancreas depend on?

Answer 37

Pancreas duodenal homeobox factor 1[PDX1] and several members of hepatocites nuclear factor (HNF). Mutations here cause monogenic diabetes mellifluous. These patients may never accrue a normal number of beta cells, which don’t function properly.

Question 38

Which hormones act via cell-surface receptors

Answer 38

Peptide hormones and catecholamines

Question 39

Which hormones act via nuclear receptors

Answer 39

Steroid and thyroid hormones

Question 40

Mutations in genes encoding any part of of the cascade from hormone receptor to action can result in?

Answer 40

Under active or over active endocrinopathy, or potentially tumor formation.