ANSWERS GRADED A+
✔✔Signaling Pathway - ✔✔A linked set of biochemical reactions that consists of
upstream events near the plasma membrane and downstream events that alter the
activity or level of target proteins
✔✔Hormones - ✔✔- First messenger molecules
- Initiate receptor activating signal
- Some common hormones include cortisol, epinephrine, insulin, testosterone, B-
estradiol, acetylcholine, nitric oxide
✔✔Second messengers - ✔✔Small nonprotein intracellular molecules that amplify
signals
✔✔cAMP - ✔✔- second messenger
- Produced from ATP by adenylate cyclase to amplify signaling
- Downregulated by hydrolyzed to AMP by cAMP phosphodiesterase
✔✔Sildenafil (Viagra) - ✔✔- inhibits cGMP phosphodiesterase leads to increases
steady state levels of cGMP and prolonged vasodilation
✔✔DAG, IP3, Ca2+ - ✔✔- second messengers
- DAG and IP3 are regulated by activity of phospholipase C
- DAG activates PKC and IP3 activates calcium release from endoplasmic reticulum
- Ca2+ binds to lots of proteins including calmodulin
✔✔5 major classes of receptor proteins - ✔✔1. Gated ion channels
2. GPCRs
3. receptor tyrosine kinases
4. TNF receptors
5. Nuclear receptors
✔✔Acetylcholine - ✔✔- Released into the synaptic cleft from presynaptic neuron
- Binds to nicotinic acetylcholine receptors
✔✔Nicotinic Acetylcholine Receptors - ✔✔- acetylcholine binding triggers
conformational change that opens ion channel
- Na+ influx, K+efflux
- Subunit composition a2ByS, Ach binding site on alpha subunits
- vestibules contain Asp and Glu negatively charged to attract Na and K, gate contains
hydrophobic Leu
- Rotation of the five transmembrane helices opens the channel
✔✔Innate immunity - ✔✔Immediate, nonspecific (skin, mucosa)
, ✔✔Adaptive Immunity - ✔✔high-affinity antibodies, memory
✔✔Antibody Structure - ✔✔-Two identical heavy chains and two identical light chains
-H2L2 heterotetramer stabilized by disulfide bonds
- protease papain cleaves antibodies to yield 2 Fab fragments that retain antigen
specificity and one Fc fragment
✔✔Variable domains on antibodies - ✔✔- Located at N terminus of heavy and light
chains, form the epitope binding site, epitopes are high affinity binging sites on antigens
✔✔Recombination of immunoglobulin genes - ✔✔Can generate tons of unique
variables V, D, and J recombination
✔✔GPCRs - ✔✔- seven membrane spanning alpha helices
- N-terminus extracellular contains carbohydrate groups
- C-terminus in cytoplasm
✔✔Rhodopsin - ✔✔- Retinal light sensor
✔✔Conformational Changes after Ligand Binding GPCR - ✔✔- Conformational changes
in the GPCR facilitate binding of Gaby complex to the receptor and then stimulates GDP
exchange for GTP in the Ga subunit.
- Ga subunit dissociates to stimulate downstream effects
✔✔Structure of G proteins - ✔✔Heterotrimeric (alpha, beta, gamma)
The human genome encode multiple subunits allowing over 1000 variations.
✔✔Shared Signaling GPCR pathways - ✔✔Ex. Glucagon and B2-adrenergic receptors
share the same Gsa-cAMP pathways, both affecting Adenyl Cyclase
✔✔Parallel Pathways GPCR - ✔✔Epinephrine activate a1-adrenergic receptors and b2-
adrenergic receptors. One pathway uses Gqa and PLC phospholipase C and the other
uses Gsa and AC. Both are net glucose export
✔✔Protein Kinase A - ✔✔activated by cAMP
Three downstream signal mechanisms
1. Phosphorylation and inhibition of enzyme needed for glycogen synthesis
2. Phosphorylation and activation of enzymes in glycogen degradation
3. Phosphorylation and activation of enzymes in glucose synthesis
NET glucose export
✔✔GEFs Guanine nucleotide exchange factor - ✔✔Promote GDP-GTP exchange,
GTPase activating proteins (GAPs) stimulate the intrinsic GTP hydrolyzing activity
1. Ligand stimulation of GEF function on GPCR