Module 2 Flashcards
(33 cards)
What are the two fundamental mechanisms of hormone action?
2 pt
- Activation of enzymes and other dynamic molecules (non-genomic)
- Modulation of gene expression (genomic)
How does activation of enzymes and other dynamic molecules work?
1 pt
- most enzymes shuttle between conformational states (active vs inactive)
- hormones induce such transitions, usually causing an activation of one or more enzymes
- enzymes often serve to activate additional enzymes - seemingly small cahnge induced by hormone-receptor binding can lead to widespread consequences within the cell
How does modulation of gene expression work?
1 pt
- by stimulating transcription of a group of genes
- this alters a cell phenotype by leading to a burst of synthesis of new proteins
- similarily, if transcription of a group of previously active genes is shut off, the corresponding proteins will soon disappear from the cell
What is the Lock and Key?
1 pt
- Determined through receptors on (or in ) target cells tat provide the specificity for hormone-cell interactions
- receptors may be components of the cell membrane, cytosolic, or nuclear elements
List the two types of location of receptor, the classes of hormones, and the principle mechanism of action for each.
6 pt
Location of Receptor
* Cell surface receptor (plasma membrane)
Classes of Hormones
* Proteins and peptides, catecholamines and eicasonoids
Principle Mechanism of Action
* Generation of 2nd messengers which alter the activity of other molecules (usually enzymes) within the cell
Location of Receptor
* Intracellular receptor (cytoplams and/or nucleus)
Classes of Hormones
* Steroid and thyroid hormones
Principle Mechanism of Action
* Alter trasncriptional activity of responsiveness genes
What are the three basic domains of the structure of a cell surface receptor
6 pt
Extracelullar domain
* someof the residues exposed interact with and bind the hormone
* ligand-binding domain (LBD)
Transmembrane domain
* hydrophobic stretches of amino acids are “comfortable” in the lipid bilayer
* anchor the receptor in the membrane
Intracellular domain
* tails or loopsof the receptor that are within the cytoplasm
* react to hormone binding by interacting with other molecules, leading to generation of 2nd messengers
* effector regions
What are some exmaples of cell surface receptors?
3 pt
- epidermal growth factor receptor
- insulin receptor
- B-adrenergic receptor
What are some characteristics of cell surface receptors?
4 pt
- Receptor molecules are neither isolated by themselves nor fixed in one location of the plasma membrane
- Other integral membrane proteins interact with the receptor to modulate its activity
- Some types of receptors cluster together in the membrane after binding hormone
- Interaction of the hormone-bound receptor with other membrane or cytoplasmic proteins is the key to generation of second messengers and transduction of the hormonal signal
What are the signal transduction mechanisms of hormonesand examples of each?
8 pt
Adenylyl Cyclase Mechanism (cAMP)
* ACTH
* LH
* FSH
* TSH
* ADH (V2 receptor)
* HCG
* MSH
* CRH
* Calcitonin
* PTH
* Glucagon
* B1 and B2 receptors
Phospholipase C Mechanism (IP3/Ca 2+)
* GnRH
* TRH
* GHRH
* Angiotensin II
* ADH (V1 receptor)
* Oxytocin
* a1 receptors
Steroid Hormone Mechanism
* Glucocorticoids
* Estrogen
* Progesterone
* Testosterone
* Aldosterone
* 1,25 - Dihydroxycholecalciferol
* Thyroid hormones
Tyrosine Kinase Mechanism
* Insulin
* IGF-1
* Growth hormone
* Prolactin
What is the 2nd messenger system of cell surface receptors?
1 pt
- The generation of second messengers and activation of specific protein kinases results in changes in the activity of the target cell
- Changes evoked by the actions of second messengers are usually rapid and amplified
What is a protein kinase (PK)?
1 pt
A kinase enzyme that modifies other proteins by chemically adding phosphorus groups to them (phosphorylation)
What is cyclic AMP signaling?
5 pt
- Hormone (1st messenger) binds to receptor
- Receptor changes shape allowing it to bind a nearby inactive G-protein - activates it
- The guanosine diphosphate (GDP) bound to G-protein is displaced by guanosine triphsophate (GTP)
- Activated G protein binds to** effector enzyme adenylate cyclase** (can stimulate OR inhibit)
- Adenylate cyclase converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP; 2nd messenger)
- cAMP activates protein kinases which phosphorylate various proteins, activating some and inactivating others. cAMP is then rapidly degraded
What is the signal amplification in signaling pathways?
1 pt
At each step of amny signal transduction pathwayys, the number of activated participants in the pathway increases
* one epinephrine-activated GPCR activates 100s of G-GTP complexes, which in turn activate 100s of adenylyl cyclase molecules, that each produce hundreds of cAMP molecules, and so on…
* overall amplification associated with epinephrine signaling is around 10^8 - fold
What is PIP-Calcium signaling?
6 pt
- Hormone (1st messenger) binds to receptor
- Receptor changes shape allowing it to bind a nearby inactivate G-protein (same as cAMP signaling)
- Activated G protein binds to and activate membrane-bound phospholiplase C (the effector enzyme)
- Phospholiplase C splits plasma-membrane phospholipid (PIP2) int diacylglycerol (DAG) and inositol triphosphate (IP3). Both molecules act as 2nd messengers.
- DAG activates protein kinase C, and IP3 triggers the release of Ca2+ from ER
- The liberated Ca2+ takes on 3rd messenger activity by:
- directly altering the activity of enxymes and plasma membrane Ca2+ channels
- binding to the intracellular regulatory protein calmodulin - activates enzymes that amplify the cellular response
What is Protein kinase activity?
4 pt
Do not use a second messenger system to activate a separate protein kinase
* have a kinase domain as part of the receptor structure
Kinase activity results in phosphorylation of tyrosine residues on other proteins
1. hormone binds to domains exposed on the cell’s surface
2. a conformational change activates kinase domains located in the cytoplasmic regions of the receptor
3. the receptor phosphorylates itself as part of the kinase activation process
4. activated receptor phosphorylates a variety of intracellular targets (e.g. enzymes)
What are intracellular receptors?
3 pt
Intracelullar receptors are receptors located inside the cell rather than on its cell membrane
Ligands are usually intracellular and extracellular lipophilic hormones
Two main groups:
1. nuclear receptors located in the cell nucleus and cytoplasm
2. other receptors located on organelles
- IP3 receptor on the endoplasmic reticulum binds 2nd messenger inositol triphosphate (IP3)
What are nuclear receptors?
3 pt
- Steroid hormones and thyroid hormone receptors
- Located inside the cell (in cytoplasm or nucleus)
- Function as ligand-dependent transcription factors - Without hormone, receptors are bound up with chaperone proteins to form complexes
1. Prevent them from binding to DNA
2. Prevent them from degradation
What is the structure of nuclear receptors?
6 pt
The N-terminal domain
* region is involved in activating or stimulating transcription by interacting with other components of the transcriptional machinery
* squence is highly variable among different receptors
DNA binding domain
* amino acids in this region are responsiblle for binding of the receptor to specific sequences of DNA
C-terminal or ligand-binding domain
* region that binds hormone
What are the three components of signaling via nuclear receptors?
6 pt
- Receptor activation
* conformational changes in the receptor induced by binding hormone
* the receptor becomes competent to bind DNA - Activated receptors bind to “hormone response elements” (HRE)
* HREs are short specific sequences of DNA located in promoters of hormone-responsive genes
* hormone-receptor complexes bind DNA at the HRE - Transcription from genes
* hormone-receptor complex functions as a transcription factor
What are hormone-receptor interactions?
1 pt
- The biological response to hormones is elicited through binding to hormone-specific recetors at the target organ
- Hormones circulate in very low concentrations, so the receptormust have high affinity and specificity for the hormone to produce a biologic response
What are some main principles of hormone-receptor binding?
5 pt
- Receptor exhibits affinity for a hormone
- Hormone-receptor interactions are specific
- A hormone may bind to more than one receptor
- Receptor number can vary (upregulated/downregulated)
- Hormone signaling must be inactivated
What is receptor affinity for a hormone?
1 pt
- Strength/stability of the bond between hormone and receptor
- Defined quantitatively by dissociation constant (KD)
What three components exist in any system containing hormones and receptor?
3 pt
- Free hormone (H)
- Free receptor (R)
- Hormone-Receptor complex (HR)
KD is a measure of affinity: the lower the KD is, the ________ the affinity of the receptor for the hormone
higher
