Bartling Study Guide Flashcards
What do cellular signal transduction cascades do?
detect, amplify and integrate external signals
What are cellular signal transduction cascades comprised of?
specific cell surface membrane receptors, effector signaling elements, regulatory proteins
What are the 6 steps of signaling?
- synthesis of a signaling molecule (ligand)
- release of the signaling molecule (ligand)
- Transport to signaling molecule to target cell
- Binding of the ligand by a specific receptor protein and change in conformation
- Change in cellular metabolism, function or development = cellular response
- Removal of ligand, termination of cell response and degradation of ligand
What are hormones?
Chemical messengers made by endocrine cells and secreted into the bloodstream.
What do hormones affect?
gene expression and protein synthesis
What hormone acts on the same cell that secreted them?
autocrine
Which type of hormone acts on other cells?
paracrine
What are types of hormones?
steroids, amine (AA derived and secreted from the thyroid and adrenal medulla), peptide, polypeptide
What are some examples of cholesterol precursors of steroid hormones?
corticosteroids (cortisol), androgens (testosterone), estrogens
Which type of hormones immediate diffuse out of endocrine cells into the bloodstream?
Steroid hormones
Are steroid hormones lipid soluble?
Yes, can cross cell membrane
Where are cytoplasmic receptors located for steroid hormones?
intracellularly, inside target cells
Are steroid hormones for peptide hormones longer acting?
steroid hormones
How do hormones lead to signal cascades?
- hormones diffuse through phospholipid bilayer
- Bind to receptor Turing on/off specific genes
- mRNA directs synthesis of new protein
- Proteins alters activity
What are amine hormones derived from?
Tyrosine or tryptophan
Where are amine hormones stored?
endocrine cells until secreted
Where can the receptor for amine hormones be located?
cell surface or intracellular
Which hormones do not immediately enter bloodstream?
polypeptide (can be stored in endocrine cell vesicles)
Which hormones are water soluble?
polypeptide hormones, do not readily pass through cell membrane
Why are polypeptide hormones termed first messengers?
bind to external receptors
What mediates intracellular effects?
second messengers- low molecular weight signaling molecules (cAMP or calcium)
What is the structure of G-protein coupled receptors?
integral membrane protein (extracellular N-terminus), 7 transmembrane spanning alpha helices, 3 extracellular and intracellular loops, Intracellular C-terminal tail membrane
T/F G-protein coupled receptors have intrinsic catalytic domains
F
What does G-protein activate?
adenylyl cyclase (converts ATP to cAMP) which activates protein kinases in the cytosol (signal cascade)
What inactivates cAMP?
Phosphodiesterase
What subunit contains the GTP-binding site and helps activate adenylyl cyclase?
Alpha subunit also contains intrinsic GTPase activity
How many bound molecules of adenylyl cyclase can stimulate Gs alpha subunits?
one molecule can stimulate many Gs alpha subunits that amplify the original hormone signal
What are some bacterial toxins that target G-proteins?
cholera toxin and Pertussis toxin (whooping cough)
What occurs when cholera toxin is present?
increase in cAMP within intestinal epithelial cells leads to phosphorylation of Cl- channels and efflux of electrolytes and water (severe diarrhea)
What happens when pertussis toxin is present?
enhances cAMP levels that inhibits neutrophil functions
Do tyrosine kinase linked receptors have intrinsic enzymatic activity?
No
What activates tyrosine kinases?
Ligand binding forms dimers activating tyrosine kinases that phosphorylate downstream targets (signal cascade)
What are intrinsic enzymatic activity receptors?
ligand-triggered protein kinases, similar to tyrosine linked receptors (form dimers upon ligand binding)
What does the ligand/receptor complex of intrinsic enzymatic activity receptors act as?
tyrosine kinase (phosphorylates other kinases) activating other protein kinases
What happens when ligand binding to ion-channel receptors occurs?
confirmation change of receptor allowing specific ions (Na+, K+) to flow through
What bacterial toxins indirecting affect ion channels?
botulinum toxin: prevents release of AcH NT and cleaves proteins involved in docking of NT vesicles
What is the steep intracellular/extracellular calciumconcentration gradient of cells?
100nM/1mM enables radical changees in Ca concentration via hormone ligation
What does calcium bind to inducing a formation change?
calmodulin, two globular domains joined by a long alpha helix
What does the calcium/calmodulin complex bind to and modify?
target proteins (kinases) that initiate signal cascades
What is the second messenger responsible for calcium mobilization?
phosphatidylinositol 4,5-bisphosphate (PIP2)
What hydrolyzes PIP2?
PLC to generate two second messengers: inositol triphosphate (IP3) and diacylglycerol (DAG)
T/F IP3 is water insoluble and can mobilize calcium
F; IP3 is water soluble and mobilizes calcium
How is DAG anchored in the plasma membrane?
due to hydrophobic fatty acid side chains
What can DAG activate?
key protein kinase C family
What can phosphatylcholine produce when hydrolyzed by other phospholipase?
lipid second messengers: DAG species generated by PLC, Phosphatidic acid generated by PLD and arachidonic acid generated by PLA2
What are key inflammatory and pain mediators?
arachidonic acid
What are arachidonic acid precursors of?
eicosanoids: prostaglandins, prostacyclins, thromboxjnes, and leukotriene (all act like hormones and signal via G-protein coupled receptors
What modulates smooth m contraction, platelet aggregation, gastric acid secretion and salt and water balance?
arachidonic acid
What is involved in arachidonic acid conversion to prostaglandins?
cyclooxyrgenase isoforms
- COX-1 and COX-2 (made only in response to inflammatory mediators)
What do prostaglandins do?
stimulate inflammation, regulate blood flow to organs such as the kidney, control ion transport across membranes, modulate synaptic transmission and induce sleep
What inhibits cyclooxygenase?
non steroidal anti-inflammatory drugs (NSAIDs) - aspirin and Ibuprofen
How do aspirin and ibuprofen inhibit cyclooxygenase?
block conversion to prostaglandins, aspirin irreversibly inactivates both forms
What are effective treatments for inflammatory conditions? (rheumatoid arthritis)
inhibitors of COX-2
What is arachidonic acid converted into leukotrienes by?
lipoxygenase
How does receptor-independent signaling work?
low molecular weight signaling molecules (NO) cross plasma membrane and directly modulate activity of catalytic domains of transmembrane receptors or cytoplasmic signal transfusing enzymes
What stimulate guanylate cyclase which generates cGMP (relaxes blood vessels)?
NO, angina symptoms treated with glyceryl trinitrate which is converted to NO
Does endocytosis require ATP?
YES
What is pinocytosis?
“drinking”, nonspecific absorption of ECF
Phagocytosis
“eating” activated any attachment of PAMPS
Receptor-mediated endocytosis
selective, form vesicles containing receptors at surface of membrane (clathrin coated vesicles form polyhedral lattice)
Movement of receptors to different membrane from the one in which it was endocytosed
transcytosis
