anatomy and physiology exam no.2

What are the endogenous/natural fat soluble ligands?

Glucocorticoids, mineralcorticoids, and sex hormones

What is an example of an endogenous glucocorticoid?

Cortisol

What is an examples of an endogenous mineralcorticoid?

Aldosterone

What are examples of endogenous sex hormones?

Estrogen, progesterone, and sex hormones

What does endogenous mean?

Made by the body

What does exogenous mean?

Comes from outside the body

What are the three exogenous glucocorticoids listed?

Prednisone, prednisolone, and dexamethasone

What is NR1?

An idle receptor in the cytoplasm

What is NR2?

An idle receptor in the nucleus

What are the components of NR1?

LBD, DBD, HSP,

What does NR1 have that NR2 does not?

Cytoplasmic receptor HSP

What does HSP stand for?

Heat shock protein

What type of dimerization occurs in NR1?

Homodimerization - NR1-NR1

What type of dimerization occurs in NR2?

Heterodimerization - NR2-RXR

Where does dimerization occur in NR1?

In the cytoplasm

Where does dimerization occur in NR2?

In the nucleus

What do NR1 and NR2 have in common?

They both bind to HRE to modulate gene transcription

How is translocation involved in NR1?

The homodimer translocates from the cytoplasm to the nucleus

How is translocation involved in NR2?

There is no translocation of the heterodimer

What amino-acid derived hormones behave like fat soluble ligands?

Thyroid hormones (T3 and T4)

What are T3 and T4 derived from?

Tyrosins and Iodine

Why are thyroid hormones an exception?

They are supposed to be water soluble, but they are fat soluble and act through NR2

How are prostaglandin an exception?

The OH group in them cause them to be water soluble

What are prostaglandin derived from?

Arachidonic acid

What does DBD stand for?

DNA-binding domain

What does LBD stand for?

Ligand-binding domain

What does inactive NR1 have?

An LBD and an HSP masking the DBD in the cytoplasm

What does HSP do in an idle/inactive NR1 cell?

It masks the DBD

What brought light to HSP?

The fruit fly experiment

What did the fruit fly experiment show?

When cells of fruit flies are exposed to high heat, there is an increase in HSP expression

What does the increase in HSP expression do for fruit flies?

It prevents cell death

What does HSP do for its receptor?

It protects the receptor, makes it more stable, and increases its affinity for ligands

In the NR1 pathway, what occurs after a ligand binds?

HSP is removed

In the NR1 pathway, what occurs after HSP is removed from NR1?

NR1 forms a homodimer and translocates from the cytoplasm to the nucleus

In the NR1 pathway, what occurs after the NR1 homodimer translocates to the nucleus

The NR1 homodimer binds to HRE

What is the co-activator function of the NR1 pathway?

HAT

What is the co-repressor function of the NR1 pathway?

HDAC

What does HAT stand for?

Histone acetylase transferase

What does HDAC stand for?

Histone deacetylase

What does HAT do?

Allow for the relaxation of histones through acetylation, resulting in more transcription and more mRNA synthesis

What does HDAC do?

Allow for the constriction of histones via deacetylation, resulting in less transcription and less mRNA synthesis

What does HRE stand for?

Hormone response element

Why is the inside of a cell negative?

Proteins and nucleic acids are negatively charged

How is lysine relevant to histone?

There are lysine residues in histone, which helps histone interact with DNA because lysine is positively charged

In the NR2 pathway, what does the ligand have to penetrate?

The plasma membrane and nuclear membrane

In the NR2 pathway, what occurs after the ligand penetrates?

The co-repressor leaves and NR2 is free to bind to RXR

In the NR2 pathway, what kind of dimer is created?

A heterodimer between NR2 and RXR

In the NR2 pathway, what is an idle NR2 bound with?

A co-repressor

What does RXR stand for?

Retinoid X receptor

In immune cells, what type of genes can cortisol co-repress?

Pro-inflammatory genes

In immune cells, what type of genes can cortisol co-activate?

Anti-inflammatory genes

What is SERM?

Selective estrogen receptor modulator/specific estrogen modulator

What is an example of a SERM?

Raloxifen

Why are SERMs called selective?

Because they can produce different estrogen-receptor effects in different tissues

Where does raloxifene have a co-activator of estrogen effect?

In bone

Where does raloxifene have a co-repressor of estrogen effect?

In breast and uterus

What makes NR2 active?

The removal of the co-repressor and binding of ligand

How are water soluble ligands/hormones produced?

They are produced before they are needed

How are water soluble ligands/hormones stored?

They are stored in a vesicle inside the cell

How are water soluble ligands/hormones released?

They are released in demand

How are fat soluble ligands/hormones produced and released?

They are produced and released in demand

How are fat soluble ligands/hormones stored?

They are never stored inside the cell

What does excess fat soluble vitamin intake lead to?

Hypervitaminosis syndrome

What are the four fat soluble vitamins?

A, D, E, and K

What is receptor desensitization/tolerance?

A decreased response after prolonged or repeated stimulation

What is receptor down regulation?

A decrease in the number of available receptors

How are most water soluble hormones released?

In pulsatile releases/episodic bursts

What is pulsatile release/episodic burst?

Release at the same periodicity and amplitude until the stimulus is over

What is biphasic release?

When there is an initial burst and then the pulses are based on the body’s needs

Why do most water soluble hormones use pulsatile release?

To avoid receptor densensitization

In the pathway of adrenergic/adrenaline receptor desensitization, what does an idle GPCR-⍺ bound with?

GDP

In the pathway of adrenergic/adrenaline receptor desensitization, what occurs after a ligand binds with the idle GPCR-⍺?

The allosteric change causes the GDP to leave and GTP comes

In the pathway of adrenergic/adrenaline receptor desensitization, what occurs after GTP comes?

⍺-GTP leaves βƔ and binds to adenylyl cyclase to create second messengers

In the pathway of adrenergic/adrenaline receptor desensitization, what occurs after ⍺-GTP leaves βƔ and binds to adenylyl cyclase?

A negative feedback loop that activates inactive GTPase and breaks ⍺+GTP down to ⍺+GDP

In the pathway of adrenergic/adrenaline receptor desensitization, what occurs after GTPase breaks down GTP?

βƔ is phosphorylated by GRK

In the pathway of adrenergic/adrenaline receptor desensitization, what occurs after βƔ is phosphorylated by GRK?

Active βƔ attracts β-arrestin

In the pathway of adrenergic/adrenaline receptor desensitization, what does βƔ + β-arrestin attract?

Cytosolic adaptor protein

In the pathway of adrenergic/adrenaline receptor desensitization, what does βƔ + β-arrestin + cytosolic adaptor protein attract?

Clathrin

In the pathway of adrenergic/adrenaline receptor desensitization, what can βƔ + β-arrestin + cytosolic adaptor protein + clathrin produce?

An endosome

In the pathway of adrenergic/adrenaline receptor desensitization, what occurs after an endosome is produced?

Phosphotase deactivates βƔ

In the pathway of adrenergic/adrenaline receptor desensitization, what occurs after βƔ is deactivated?

Ubiquitin coats the endosome for the lysosome to eat

What is GRK?

A G-protein receptor kinase enzyme

In the pathway of adrenergic/adrenaline receptor desensitization, what prevents the binding of ⍺+GDP?

The attraction of β-arrestin to active βƔ

What is clathrin?

An immunoglobin-like structure

What is a lysosome?

A cell organelle that functions as a predator or paper shredder and attacks the ubiquitin-coated endosomes and does the permanent destruction of receptors

What is adenylyl cyclase?

It is an effector protein like PLC that

What is PLC?

Phospholipase C

What is an endosome?

Pinched off plasma membrane bound vesicles

What has slow GTPase activity in the pathway of adrenergic/adrenaline receptor desensitization?

The G⍺ subunit

What is the function of ubiquitin?

It tags the internalized receptor/endosome for destruction

Receptor recycling is the function of which enzyme?

Phosphatase

Permanent receptor destruction is function of which organelle?

Lysosome

What is a nerve?

A bundle of axons in the PNS

What is a tract?

A bundle of axons in the CNS

What is a ganglia?

A cluster of cell bodies/somas in the PNS

What is a nucleus?

A cluster of cell bodies/somas in CNS

What is a endolysosome?

Endosome + lysosome

What does TGN site stand for?

Trans-golgi network site

What does the TGN site do with temporarily internalized receptors?

Helps recycle them back to the plasma membrane

What are the three organizational divisions of the nervous system?

The CNS, PNS, and ANS