Biol 218 1st Edition Final Exam Study GuideChapter 16~Delta: inhibitory signal- Differentiates cells from one another, signal received by notchTrimeric: 3 protein subunits (alpha, beta, gamma)- Play role in activating G-protein- Receptor stays active while signal is bound=> amplificationViagra: sildenafil citrate- Blocks PDE5 (phosphodiesterase type 5: used to break down cGMP=> prolonged relaxation of smooth muscle)- If cGMP isn’t broken down then it causes the widening of vessels leading to an erection - Remember that prolonged signal prolongs its actionSignaling Cascades: formed by protein kinases (tyrosine or serine/threonine)1. Relay2. Transduce & amplify3. Integrate4. Distribute Ion Channel Coupled receptors:- Work when flow of ions across plasma membrane changes the membrane potential & also produces an electric current- Examples: neurotransmitters at postsynaptic membraneEnzyme Coupled Receptors:- Either act as enzymes or associate with enzymes inside the cell- Methods: o Dimer activates catalytic domaino Signal molecule binds & results in activated associated enzymeG-protein coupled receptors: activates membrane bound trimeric GTP binding proteins- Process: signal molecules binds to receptor & is activated unbinds from receptor and binds to enzyme to activate it- Can lead to drug dependence- Maintains homeostasis by desensitizing after activationo Desensitizationinternalizationdegradationrecycling receptor- Largest type of cell surface receptors- Where vast majority of drugs work (1/2)- Are ancient because they are even found in bacteria- There are more than 700 in humans and more of them are “orphan receptors”- Essential signaling molecule is beta-arrestinG1-inhibitory: blocks G1- Associated with pertussis toxin (whopping cough)G-protein targets ion channel: - Results in immediate change in state and behavior of cells- These channels are regulated by polarization which inhibits electrical excitability- Example: used to slow down heartbeato Acetylcholine is released and binds to GPCR on heart pacemaker cells slower hear muscle contractions because K+ ion channel opens polarization of membraneG-proteins target membrane bound enzymes:- G-proteins activate these enzymes:o Activated alpha subunit of G-protein binds to enzyme activated enzyme production of additional intracellular signaling molecules alongside extracellular signals Intracellular: adenylyl cyclase and phospholipase CcAMP: second messenger signaling molecule- Generated by adenylyl cyclase, in cytoplasm- Stimulate protein kinase A (PKA) so that it will carry on cellular effects- Degraded by cAMP phosphodiesterase- Is water soluble to allow movement through cytoplasm and nucleus- Serine/threonine protein kinaseGs-stimulatory: cholera toxin- Blocks Gs which causes prolonged stimulation of gut- Stimulates production of cAMPFast pathway: would take microseconds- Process: active GPCRactive G-protein adenylyl cyclase bindscAMPactivates PKAmetabolic kinase cell effects- Example: adrenaline stimulates glycogen breakdown in skeletal muscleSlow pathway: could take days or more- Process: active GPCRactive G-proteinadenylyl cyclase bindsactive PKAnucleustranscription factorcell effect- Example: cAMP can mediate signals from membrane to effect gene expressionPhospholipase C (PLC): - Membrane bound- Produces IP3 inositol triophosphate & diacylglycerol by cleaving membrane protein- Process: GPCR activatedactivated PLC activates IP3 & DAGMAP-kinases: - Activated by Ras & influences protein activity & gene expression- Process: RTK Ras binds MAPKKK MAPKKMAPK protein activity/gene expressionQuestions:What effects cell differentiation during development? - Signals, which can also induce different responses on different target cellsWhat regulates transcription directly?- Hydrophobic hormones- Examples: cortisol, estradiol, thyroxine, testosteroneHow does the G-protein turn off?- Switches itself off by hydrolyzing GTP:1. Activated alpha subunit activates target protein2. Hydrolysis of GTP by subunit inactivates the subunit & causes it to disassociate from target protein3. Inactive alpha reassembles with beta and gamma complex to reform inactive G-protein4. Inactive target protein & G-proteinHow is homeostasis maintained?- By signaling cascades & feedback regulationWhy are drugs so effective?- They are exogenous & affect cell surface receptors because they are structurally similar to proteins made inside body (endogenous) How do signaling molecules increase the diversity of cellular response?- By interacting with more than one type of receptor- Example: acetylcholine1. Ion channel receptor in skeletal muscle: caused more contractions2. G-protein coupled receptor in heart cells: decrease in rate and force of contractionsWhat are the effects of different ligands acting on the same receptor?- Cause different subtypes of G-proteins to be activated in different amounts which leads to different effectsChapter 18~Critical checkpoints: molecular brakes- Ensure each phase of cell cycle is completed properly before starting next phase- Must have DNA replication before mitosisG1: comes before S phase- Cell grows and makes proteinsS-phase: part of interphase- Where chromosomes are copied- Long, thin, and tangled thread of DNA that is not easily distinguishable with light microscope- Loose to allow access for replication- Occupy different specific territories in nucleus, not all mixed - Takes 8 hours- Heterochromatin on edges and nucleolus with genesG2: comes before m phase- Cell prepares to divide, gap phase where cell grows and makes proteinsM: mitosis- Phase where growth stops and cell divides - DNA is dense, compact and easily visual - Occurs after G2- Most m-Cdk activityG1/S checkpoint: initiated after DNA damage - Allows cell to repair damage before DNA is copied- “Are there sufficient nutrients and growth factors?”Intra-S checkpoint: initiated by DNA damage- Slows DNA replication- “Does replication need to be slowed in order to fix DNA damage?”G2/M Checkpoint: - Stops cell to allow repair prior to chromosome segregation and mitosis- “Are all chromosomes properly attached to mitotic spindle?”- “Is all DNA damage repaired?”CDK’s: cyclins made during interphase- Kinases of cell cycle control system - Activated al appropriate times the quickly deactivated- Must bind to regulatory cyclin proteins to be
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