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112 Cards in this Set
- Front
- Back
Chromatid
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Early M-phase chromosome has two sister copies
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Centromere
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Point at which two chromatids are joined
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Telomere
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Form caps at the ends of each chromatid
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M-Phase
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Mitosis (nuclear division)
Cytokinesis (cytoplasmic division) |
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Interphase
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G1, S, and G2 phases of the cell cycle
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G1 Checkpoint
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Is environment favorable? Proper nutrients and growth factors
If yes, enter S-phase |
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G2 Checkpoint
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Is all DNA replicated?
Is all DNA damage repaired? If yes, enter mitosis |
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Checkpoint in Mitosis
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Are all chromosomes properly attached to mitotic spindle?
If yes, pull duplicated chromosomes apart |
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Cdks
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Kinases of the cell control cycle - activated at appropriate times in cell cycle & then are quickly deactivated
To become active it must be phosphorylated at one site to become primed for action |
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Cyclins
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No enzymatic activity but have to bind to Cdks to make them enzymatically active
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Cdk-Cyclin complexes
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Trigger entry into S-phase or M-phase
cell cycle control mechanisms are highly conserved through evolution Changes in cellular concentrations of cyclins controls the cell cycle by translation and protein degredation 2 inhibitory phosphates are placed until checks being verified, if ok dephosphoylation of the inhibitory phosphates activates the complex |
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G1-Cdk
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Cyclin D + Cdk4,Cdk6
**Three D cyclins in mammals(D1, D2, D3)** |
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G1/S-Cdk
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Cyclin E + Cdk2
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S-Cdk
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Cyclin A + Cdk2
Triggers S-phase by facilitating the activating of the replication machine Also stops re-replication by inducing the degradation of Cdc6 |
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M-Cdk
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Cyclin B + Cdk1
Triggers M-phase - condensation of the chromosomes Activated by the phosphate cDc25 removing the inhibitory phosphate Positively feeds back to further increase mitotic signals - Amplification **Cdk1 was originally Cdc2 in vertebrates) |
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G0-Phase
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Resting phase, quiescence
Transition out of G0 requires accumulation of G1 cyclins, induced by signals from the environment |
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Origins of Replication
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Site of DNA synthesis
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Origin Recognition Complex (ORC)
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Remains bound to origins of replication throughout the cell cycle, serves as a landing pad for regulatory proteins that bind before the S-phase
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Cdc6
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Regulatory protein.
Concentration increases in early G1 binding of Cdc6 promotes binding of additional proteins to form a pre-replicative complex |
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Cohesin Rings
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Hold sister chromatids together, vital to correct division of the chromosomes
Cleaved late in mitosis |
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Condensins
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Assemble on each individual chromatid at the start of M-phase to coil up the DNA to help chromatids condense
Triggered by M-Cdk |
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Prophase
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Replicated chromosomes condense, the mitotic spindle, outside the nucleus, assembles between the two centromeres
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Prometaphase
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Breakdown of the nuclear envelope. Chromosomes can now attach to mitotic spindle microtubules via their kinetochores and undergo active movement
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Metaphase
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Chromosomes aligned on the metaphase plate, midway between the spindle poles. The paired kinetochore microtubules on each chromosome attach to opposite poles of the spindle
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Anaphase
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Sister chromatids synchronously separate, each pulled slowly toward the pole it is attached to, chromosome segregation
Initiated by the release of cohesins |
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Telophase
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Two sets of chromosomes arrive at the poles of the spindle, new nuclear envelope reassembles around each set, completing the formation of two nuclei and marking the end of mitosis. COntractile ring starts to form.
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Cytokinesis
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Cytoplasm is divided into two by contractile ring of actin and myosin filaments, creating two daughter cells.
In plant cells involves formation of new cell wall. |
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Chromosomal Segregation
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Facilitated by the cytoskeleton.
3 types of Microtubules Aster Kinetochore Interpolar |
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Centrosome Cycle
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Duplication of the centrosome (during interphase) and separation of the two new centrosomes (at the beginning of mitosis), to form the poles of the mitotic spindle (the aster)
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Mitotic Spindle Assembly
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Microtubles continuously growing and shrinking "Dynamic Instability"
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Spindle Poles
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During M-phase microtubules growing/shrinking from both centrosomes
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Interpolar Microtubules
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Microtubles that interact with tubules from the opposite centrosome and stabalize, assembly is driven by large motor proteins that crosslink and stabalize
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Kinetochore
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Microtubule attachment point on the centromere, one on each side of chromatid
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Annaphase Promoting Complex (APC)
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Degrades securin which allows separase to become active which degrades the cohesin rings
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Organelle Division
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-Mitochondria and chloroplasts duplicate themselves and are equally distributed during cell division
-ER is cut in two during cytokinesis -Golgi fragmented during M-phase and fragments associate w/ spindle microtubules "hitch a ride" to poles -Soluble proteins in cytoplasm are inherited randomly during cytokinesis |
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Apoptosis
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Cell Suicide - controlled death, initiated in response to cell signals
Initiated to control amount of cells or remove old/dying cells Quick, clean process, organic material can be recycled Organ size is regulated by a balance between birth and death rates |
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Caspase
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Family of Proteases responsible for regulating apoptosis
inactive precaspases cleaved in response to cellular signal Initiated caspases cascade, amplifying the response They breakdown nuclear lamina and other cytosolic proteins to dismantle the cell |
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BcL-2 Family of Proteins
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Anti-Apoptotic - Bcl2, Bcl-XL (Pro-survival, block caspase activation)
Pro-Apoptotic - Bik, Bim, Bad, Bax, Bak (Pro-Death, release cytochrome C from mitochondria which activates caspases) |
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Apoptosome
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1. Release of cytochrome C from mitochonrdrion activated by Bax/Bak
2. Activation of adaptor protein by cytochrom C 3. Assembly of activated adaptor proteins 4. Recruitment of procaspase-9 molecules 5. Activation of procaspase-9 w/in apoptosome 6. Caspase cascade leading to apptosis |
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Pro Survival Factors
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Suppress apoptosis
Can be influenced by other surrounding cells |
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Mitogens
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Stimulate cell division by "overriding" cell cycle checkpoints
Rb acts as transcriptional repressor - activated G1/S-Cdk phosphorylates Rb releasing inhibition allowing transcription, translation, and cell proliferation - initiated by mitogen |
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Mitogen Pathway
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Rb acts as transcriptional repressor - activated G1/S-Cdk phosphorylates Rb releasing inhibition allowing transcription, translation, and cell proliferation - initiated by mitogen
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Growth Factors
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Stimulate cell growth (increase in size and mass) by promoting gene expression and suppressing protein degradation
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Growth Factor Pathway
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Facilitate growth of cell by promoting protein synthesis and blocking degradation, some growth factors can stimulate growth and cell division, Eg, EGF, PDGF
Can also tell cells to stop growing. |
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Myostatin
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Inhibitory growth factor that tells our muscles to stop growing.
Super cows have myostatin mutation |
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Signaling Cascades
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Extracellular Signal molecule-->
Receptor Protein--> Intracellular signaling protein--> Effector protein--> Cell response |
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Cell Signals
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Endocrine - Hormone
Paracrine - Local mediator Neuronal - Neurotransmitter Contact-Dependent - membrane-bound signal molecule |
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Adrenaline
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Hormone
Adrenal Gland Derivative of the amino acid tyrosine Increases blood pressure, heart rate, and metabolism |
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Cortisol
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Hormone
Adrenal Gland Steroid (derivative of cholesterol) affects metabolism of proteins, carbs, and lipids |
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Estradiol
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Hormone
Ovaries Steroid (derivative of cholesterol) Induces and maintains secondary female characteristics |
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Glucagon
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Hormone
a Cells of pancreas Peptide Stimulates glucose synthesis, glycogen breakdown, and lipid breakdown |
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Insulin
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Hormone
B Cells of Pancreas Protein Stimulates glucose uptake, protein synthesis, and lipid synthesis |
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Testosterone
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Hormone
Testis Steroid (derivative of cholesterol) Induces and maintains secondary male sexual characteristics |
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Thyroid Hormone (Thyroxine)
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Hormone
Thyroid Gland Derivative of the amino acid tyrosine stimulates metabolism of many cell types |
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Epidermal Growth Factor (EGP)
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Paracrine
Various cells Protein Stimulates epidermal and many other cell types to proliferate |
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Platelet-derived Growth Factor (PDGF)
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Paracrine
Various cells including blood platelets Protein Stimulates many cell types to proliferate |
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Nerve Growth Factor (NGF)
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Paracrine
Various innervated tissues Protein Promotes survival of certain classes of neurons; promotes growth of their axons |
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Transforming Growth Factor-B (TGF-B)
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Paracrine
Many cell types Protein Inhibits cell proliferation; stimulates extracellular matrix production |
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Histamine
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Paracrine
Mast cells Derivative of the amino acid histidine Causes blood vessels to dilate and become leaky; helping to cause inflammation |
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Acetylcholine
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Neurotransmitter
Nerve Terminals Derivative of choline Excitatory neurotransmitter at many nerve-muscle synapses and in the central nervous system |
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y-Aminobutyric Acid (GABA)
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Neurotransmitter
Nerve terminals Derivative of the amino acid glutamic acid Inhibitory Neurotransmitter in central nervous system |
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Delta
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Contact-Dependent
Prospective neurons; various other developing cell types Transmembrane protein Inhibits neighboring cells from becoming specialized in the same way as the signaling cell |
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Fast Response Time
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Phosphorylation turning proteins On and Off
Altered protein function Negative feedback, allosteric modification, complexing "protein machines", post-translational modification "phosphorylation" |
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Slow Response Time
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Transcription and translation; making more proteins
Altered protein synthesis Amount of substrate, amount of enzyme, subcellular location of enzyme |
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Hydrophobic Hormones
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Can regulate transcription directly
Cortisol, Estradiol, Testosterone, Thyroxine |
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Nitric Oxide
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Gas
Acts as signaling molecule Released from endothelial cells and diffuses into smooth muscle cells (via activation of cGMP) |
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Viagra
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Blocks phosphatase which inhibits cGMP causing prolonged relaxation of smooth muscle (vasodilation)
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Ion-channel Coupled Receptor
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Flow of ions across the plasma membrane - changes the membrane potential and produces an electric current
eg - neurotransmitters at the postsynaptic membrane |
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G-Protein Coupled Receptor (GPCR)
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Activate membrane-bound trimeric GTP-binding proteins (G Proteins)
Then activate either an enzyme or an ion channel in the plasma membrane Largest family of cell receptors, more than 700 in humans Ancient even in bacteria |
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Trimeric G Protein
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3 protein sub-units
Passes a series of conformational changes to relay the signal Unstimulated = a GDP bound Stimulated = a decreased affinity for GDP - replace GDP w/ GTP Activated G proteins can interact with target proteins in the plasma membrane Switches itself off by hydrolyzing GTP |
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G Protein Types
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Gi - inhibitory (pertussis toxin blocks a Gi generating a prolonged cough
Gs - stimulatory (cholera toxin blocks a Gs causing prolonged stimulation of the gut Golf - olfactory |
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G Protein Functions
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Some regulate ion channels - immediate change in the state and behavior of cells
Some activate membrane-bound enzymes Interaction w/ enzyme leads to production of intracellular signaling molecules - targets Adenylyl cyclase and Phospholipase C |
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Enzyme-coupled Receptor
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Signal in form of a dimer activates catalytic domain or signal molecule activates associated enzyme
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Valium and Barbituates
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GABA
Relief of anxiety; sedation |
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Nicotine
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Acetylcholine
Constriction of blood vessels; elevation of blood pressure |
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Morphine and Heroin
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Endorphins and enkephalians
Analgesia (relief of pain); euphoria |
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Curare
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Acetylcholine
Blockage of neuromuscular transmission; resulting in paralysis |
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Strychnine
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Glycine
Blockage of inhibitory synapses in spinal cord and brain, resulting in seizures and muscle spasms |
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Adenylyl Cyclase
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Produces cyclic AMP (cAMP)
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Phospholipase C
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Produces inositol triphosphate (IP3) and diacylglycerol (DAG)
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cAMP
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Second messenger signal
Serine/theronine protein kinase generated by Adenylyl cyclase degraded by cAMP phosphodiesterase Binding cAMP activates the kinase Exerts cellular effects via Protein Kinase A (PKA) Water soluable, moves through cytoplasm to deliver message to other organelles, even nucleus |
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cAMP Mediated Responses
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Adrenaline - Heart - increase in heart rate and force of contraction
Adrenaline - Skeletal muscle - glycogen breakdown Adrenaline, ACTH, Glucagon - fat - fat breakdown ACTH - adrenal gland - cortisol secretion |
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Phospholipase C (PLC)
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Membrane bound
Generates IP3 and DAG by cleaving a membrane protein (inositol phospholipid |
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Phospholipase C Mediated Responses
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Vasopressin - Liver - glycogen breakdown
Acetylcholine - pancreas - secretion of amylase Acetycholine - smooth muscle - contraction Thrombin - blood platelets - aggregation |
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Calmodulin
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Changes shape in response to calcium binding to activate other proteins
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Tissues
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Cooperative assembly of cells
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Extra-Cellular Matrix
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ECM
Complex network of polysaccarides such as glycosaminoglycans or cellulose and proteins such as collagen secreted by cells They act as a structural component of tissues that also influence their development and physiology Plants = cell wall, Animals = lots in bones and tendon, not so much in muscles and skin |
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Plant Cell Wall
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Rigidity to protect contents, needed to resist turgid pressure
Cellulose microfibrils - provide strength Polysaccarides - act as crosslinkers Pectin - acts as a filler to resist compression Lamella - a pectin-rich layer that cements layers together |
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Cellulose
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Not made inside cell
Synthesized on cell surface by "Cellulose Synthase Complexes" Transport the components out of the cell and make the cellulose changes Movement of these enzymes in the membrane dictate how the microfibrils are "spun" |
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Connective Tissues
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Bone, cartilage, dermis of skin, jelly that fills eye
Bulk of it is ECM Carries mechanical load |
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Collagen
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In all strength comes from the fibrous protein
Provides tensile strength Mammals have 20 different collagen genes, 25% of protein mass 3 collagen polypeptides wound together to form superhelix |
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Fibroblasts
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Connective tissue cells - make and inhabit the ECM
ECM generated intra-cellularly and secreted (exocytosis) |
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Ehlers-Danlos Syndrome
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EDS also known as Cutis hyperelastica
Collagen fibrils do not assemble properly = stretchable skin |
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Integrins
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Cell surface receptor and act as signaling molecules between ECM and cell
Couple the matrix to the cytoskeleton via fibronectin - "grabs" fibronectin to pull and move the cell w/in the ECM Connections to the intracellular cytoskeleton stop it from being ripped out Only located in Firbroblasts |
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GAGs
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Glycisaminoglycans (polysaccharides)
Proteoglycans (proteins) Concentration of GAGs vs. collagen gives ECM it's consistency Gels that fill up space and resist compression |
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Epithelia
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Epithelium
Cells joined together side-to-side Stratified - sheets Simple epithelium - only one cell thick, thick gut lining Creates a barrier, takes up nutrients and exports waste, contains receptors for environmental signals, protects interior of organism from invading microorganisms and fluid loss, facilitates or stops movement of cells Polar and rest on Basal lamina |
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Basal Lamina
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Made of Type IV collagen and a protein called Laminin
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Laminin
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Binds to epithelial cell integrin's allowing communication between the basal lamina and the epithelium
Laminin "firbronectin of the epithelium" |
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Tight Junctions
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Seals neighboring cells together in an elithelial sheet to prevent leakage of molecules between them
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Adherens Junction
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Joins an actin bundle in one cell to a similar bundle in a neighboring cell
Cadherin's join cells together tightly by homophilic bonding Can form strong continuous "belt" around the epithelium |
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Desmosome
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Joins the intermediate filaments in one cell to those in a neighbor
Cadherin molecules bind to internal keratin filaments, forming thick rope like structures which are welded to the plasma membrane, provides strength, common in skin |
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Gap Junction
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Forms channels that allow small water-soluble molecules, including ions, to pass from one cell to another
Signaling can change size and permeability of gap junctions to respond to the environment Think dopamine and eyes switching from rods to cones |
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Hemidesmosomes
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Anchors intermediate filaments in a cell to the basal lamina
Anchor epithelial to other tissues via integrins |
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Connexons
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Type of Gap Junction
Form channels across two plasma membranes Provides both electrical and metabolic coupling between cells |
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Tissue Renewal
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Cyclical
1. Cell Communication 2. Selective cell-cell adhesion 3. Cell memory When and how often cells are renewed varies greatly by tissue type |
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Stem Cells
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Generate a continuous supply of terminally differentiated cells
can divide w/out limits or become differentiated Adult stem cells have undergone first layer differentiation to define progeny type Status maintained by the WNT pathway |
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Terminally Differentiated
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Cells that cannot divide for themselves
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Hemopoietic Stem Cell
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Can produce all the cells of the blood
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WNT Pathway
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When inactive = no cell proliferation
When active = cell proliferation When WNT gene is turned off cell becomes terminally differentiated and moves up in the chain |
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B-Catenin
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If degraded before entering the nucleus then cell is differentiated
When WNT is expressed it triggers a signaling cascade that stops the degredation of B-Catenin which moves to the nucleus to activate "stem cell specific" gene transcription |
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Embryonic Stem Cell
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Can give rise to any other type of cell in an organism
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Induced Pluripotent Cells
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Can create and iPS stem cell by taking a fibroblast and introducing three key genes
Sox2 Oct3/4 Klf4 iPS SC can then differentiate into many other types of cells |