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49 Cards in this Set
- Front
- Back
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What are the 3 types of extracellular messengers?
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Hormones
Neurotransmiitters Eicosanoids |
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Describe hormone extracellular messengers. What are the 4 types? Give examples.
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Peptides: insulin, glucagon (secreted from pancreas)
Catecholamines - epinephrine, norepinephrine. (Released from adrenal gland, cns). Made from decarboxylation of aromatic acids Steroids: Mineralocorticoids, glucocorticoids, progestins. made from cholesterol Thyroids: T3, T4 (thyroxin). Synthesized from tyrosine, iodine. |
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What are 3 examples of NTs?
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Acetychole, catecholamines, GABA.
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What are eicosanoids?
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PGs, LTs, TXs
Made from C20 arachadonic acid |
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What is the half life of hydrophilic versus lipophilic hormones?
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Hydrophilic - short
lipophilic - long |
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What is the receptor site of hydrophilic vs. lipophilic hormones?
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hydrophilic - plasma membrane
lipophilic - nucleus |
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How do hydrophilic vs. lipophilic hormones travel in blood?
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hydrophilic - free
lipophilic - protein transporter |
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What are 4 targets of extracellular messengers
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Metabolic enzymes - hormones phosphorylate or dephosphorylate enzymes (covalent modification)
ion channels - NTs open/close ion channels cytoskeletal proteins - can modify actin/myosin for muscle contraction transcription factors - (ie. steroids and thyroid hormones) can upregulate transcription factors to increase protein synthesis |
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What is autocrine signaling?
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messenger acts on the cell that released them
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What is paracrine signaling?
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messenger acts on neighboring cells
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What is endocrine signaling
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Messenger acts on cells that are faraway from site of production/release. Must be transported to site of action.
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Why is G-protein called a serpentine receptor?
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B/c it has a 7-transmembrane domain.
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What are the two types of G proteins?
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Monomeric (small G protein) and Heteromeric (3 subunits - alpha beta gamma)
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What are the 2 states of G proteins?
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Bound to GDP - all 3 subunits bound together, G protein is inactive
Bound to GTP - active. Alpha subunit dissociates and acts on effector molecule. Alpha subunit has intrinsic GTPase activity. |
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name 4 types of heteromeric G proteins, and describe what they do
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Gs - stimulates Adenylate cyclase
Gi - inhibits AC Gt - transducin (stimulates c-GMP phosphodiesterase) Gq - stimulates PLC -beta |
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What happens to alpha-GTP after it stimulates AC?
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It is hydrolyzed to GDP. Rejoins the Beta, gamma subunits, G protein goes back to being inactive. Terminates signal.
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What binds to the Beta-adrenergic receptor?
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Epinephrine
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How is cAMP made? broken down?
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5'AMP --> cAMP with adenylate cyclase
cAMP --> 5'AMP with PDE |
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What agent inhibits PDE, thus increasing cAMP? Give 3 examples
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Methylxanthines - examples: caffeine, theophylline (to treat asthma), forskoline (activates AC)
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What is the structure of protein kinase A when active and when inactive.
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4 subunits (2 regulatory, 2 catalytic)
inactive: all subunits bound together active: cAMP binds to R subunits, releases C subunits. phosphorylates/activates enzymes. |
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How do epinephrine and Ach act on heart muscle contraction?
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Epi stimulates Gs (= + cAMP via AC) = heart contraction
Ach stimulates Gi (decr. cAMP..) - dampens the epi effect |
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What is receptor desensitization/
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Phosphorylation of stimualted receptor by Beta-adrenergic receptor kinase (BARK), then arrestin binds. Receptor can no longer bind Gs.
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How does cholera happen?
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Cholera toxin binds to GM1 gangliosides on surface of intestinal epithelial cells. It's endocytosed, migrates to the endosome.
A1 is released from complex, transfers ADP-ribose from NAD+ to Gs-alpha. ADP-ribosylated alpha subunit can still bind GTP, stimulate AC - but no GTPase activity. So Gs-alpha is locked in active, GTP-bound form. --> continuous excessive stimulation of AC --> + cAMP --> + Na+ and water in the intestinal lumen. --> severe diarrhea |
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What causes whooping cough?
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Whooping cough: toxin ADP-ribosylates the alpha-subunit of Gi, so Gi cant swtich GDP for GTP. Gi is locked in inactive state (cannot inhibit AC). So +cAMP = + mucous secretion by respiratory epithelial cells and whooping cough
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what causes diphtheria?
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Diphtheria: toxin catalyzes ADP-ribosylation of EF-2 (G protein which participates in mRNA-dependent protein synthesis). Toxin inhibits protein synthesis, causes cell death.
- tonsils, throat, nose and/or skin |
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What are the 4 subtypes of PLC? What does PLC do?
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-alpha, beta, gamma,sigma
- hydrolyzes PIP2 --> IP3 and DAG |
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How is the effect of IP3 terminated?
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Conv to IP4 or IP2/IP1/free inositol
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What does Lithium do?
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Inhibit dephosphorylation of IP3 to free inositol. So no free inositol - = less resynthesis of PIP2.
Decreased PIP2 dampens effect of neurotransmitters that use IP3/DAG pathway |
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What is myosin light-chain kinase?
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Phosphorylates MLC, leading to smooth muscle contraction.
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How can you produce smooth muscle relaxation?
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Decrease Ca++ conc
Dephosphorylation of MLC by phosphatase |
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What do pharbol esters do?
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DAG analogs - stimulate PKC
mitogenic (tumor promoters) |
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What do IP3 and DAG do?
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IP3 binds Ca++ channels in the ER, releasing Ca into the cytosol.
DAG stimulates PK C (which phosphorylates...cell growth/proliferation) DAG can form lysophosphatidic acid (= cell growth,prolif) Deacetylation of DAGs --> arachodonic acid --> TXs, PGs, LTs |
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Whats the difference between rods and cones?
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Rods - dark/dim light
Cones - bright light, can see color |
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Where are rods/cones located?
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rods - everywhere except fovea
cones - all over retina |
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How many types of rhodopsin do rods/cones have?
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rods -1
cones -3 (red,green,blue) |
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Describe the structure of a rod.
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outer segment - rhodopsin
inner segment - mitochondria, ER, nucleus glutamate-releasing synaptic terminal at the base. |
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What is the structure of rhodopsin in the dark? in the light?
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dark -- opsin + 11-cis-retinal
light -- opsin + All-trans-retinal |
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What is transducin?
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Gt - activated by conformational change of rhodopsin. Activates cGMP PDE.
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What is the sequence of events in rod cells in the dark?
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high cGMP levels
opens cGMP-gated Na/Ca channels depolarization Glutamate release at synaptic terminal Inhibits bipolar cells |
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What is the sequence of events in rod cells in the light?
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light strikes rhodopsin, 11 cis retinal changes to all-trans-retinal
rhodopsin activates transducin, alpha GTP dissociates and activates PDE PDE degrades cGMP Na/Ca channels close hyperpolarization No glutamate release from synaptic terminal |
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How is rhodopsin returned to the dark state?
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- Rhodopsin kinase phosphorylates rhodopsin, arrestin binds to rhodopsin. transducin cannot bind
- hydrolysis of GTP to GDP (so transducin comes together - inactive) - Resynthesis of cGMP - Return of all-trans-retinal to 11-cis-retinal |
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How does ANP (Atrial natriuretic protein) work?
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ANP binds to rec --> stimulates GC producing cGMP. cGMP activates protein kinase G --> phosphorylates proteins --> decreases blood pressure, increases urine volume, relaxes vascular smooth muscle.
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How does NO-mediated vasodilation work?
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NO synthase synthesizes NO from Arg in vascular endothelial cells (enz is stim by Ca calmodulin complex). NO activates GC in vascular smooth muscle (which produced cGMP), causes smooth muscle to relax. (decr blood pressure)
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How does Viagra work?
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Viagra inhibits cGMP-dep PDE (so cGMP cant degrade to 5'-GMP) - so muscle relaxation
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How does the epidermal growth factor activate proteins?
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EGF receptor has tyrosine kinase activity. Binds EGF, ECF receptors dimerize and phosphorylate each other at tyrosine residues. Phosphorylated tyrosine residues = docking sites for cytoplasmic and membrane assoc proteins. Receptors then phosphorylate those proteins.
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How does the insulin receptor work?
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Insulin rec has tyrosine kinase activity.
Insulin binding--> autophosphorylation of receptor. Rec then binds the phosphoprotein "insulin receptor substrate 1" (IRS-1), which becomes phosphorylated on tyrosine residues. These residues serve as docking sites for SH2-containing proteins |
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What happens after IRS-1, EGF receptors get phosphorylated at the tyrosine residues? (3)
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Phos at tyrosine residues Activates PLC-gamma-1, which hydrolyzes PIP2 --> IP3 + DAG
IP3 releases intracellular Ca, DAG activates PKC _____ Phosphorylation of tyrosine residues activates PI-3 Kinase PI 3 kinase phosphorylates PIP2 to form PIP3 PIP3 activates PDK1 PDK1 phosphorylates and activates PKB (Akt) --> stim of glycogoen synthase _____ GRB/SOS activated by EGF/insulin Moves to membrane, couples Ras with phosphorylated EGF receptor or IRS-1. Ras is activated Ras acts. Raf Raf acts MEK MEK acts ERK (MAPK). ERK phosphorylates and activates proteins/nuclear TFs... terminaetd when Ras GTP --> Ras GDP (by another GTPase activating protein -= GAP) |
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How do Ach and GABA and glutamate work?
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Ach:
nicotinic - opens Na/K channels muscarinic - 7-transmembrane receptors coupled to DAG/IP3 signaling GABA - inhibitory NT. Opens Cl- channels glutamate - opens Ca++ channel |
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What happens when steroid hormone binds to glucocorticoid receptor?
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Conformational change occurs which releases HSP (heat shock protein) from receptor and exposes DNA binding site. Receptor then binds to Hormone Response Element, causes increased transcription
note: thyroid hormones, retinoic acid, vitamin D just bind to receptors which complex with HRE. (no HSP) |
