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Week 1 Flashcards

1
Q

What are stem cells and the different types?

A
  • Stem Cells: have unique to differentiate into other cell types
    • Pluripotent (embryonic stem cell): can differentiate into any cell line
    • Multipotent: can differentiate into limited cell lines (ex: bone marrow)
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2
Q

What are terminally differentiated cells?

A
  • Terminally Differentiated: adult cell that enters into non-dividing state (ex: skeletal cells, neurons)
    • Specialized stem cells can be present for repair mechanisms
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3
Q

List the steps of the interphase, their main functions and how it is regulated.

A
  • Interphase
    • Gap1 Phase: growth phase where cells can enter into G0 (no division)
    • S Phase: replication
    • Gap2 Phase: growth phase
  • Checkpoints are regulated by [Cdk]
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4
Q

List the steps of the mitosis, their main functions and how it is regulated.

A
  • Mitosis
    • Prophase: duplicated centrosomes; mitotic spindles form (microtubules)
    • Metaphase: nuclear envelope breakdown; chromosomes align
    • Anaphase: chromatids separate
    • Telophase: nuclear envelope reforms
    • Cytokinesis: cells divide using actin mechanism
  • Checkpoints are regulated by [Cdk]
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5
Q

What is cell signaling and how does the process work?

A
  • Change in external environment → Change in receptor binding → Secondary messengers → amplify response → adapts gene expression
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6
Q

What are the types of intracellular signaling and how do they work?

A
  • Intercellular Signaling
    • Contact-dependent: membrane-bound receptor interaction
    • Paracrine: mediator molecule secreted to local environment
    • Synaptic: neurotransmitters (think ACh!)
    • Endocrine: hormones through bloodstream
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7
Q

What are the differences between Eukaryotic and Prokaryotic cells?

A
  • Eukaryotic has membrane-bound organelles for specialized functions, nucleus, and mitochondria while prokaryotic utilizes cytosol for all functions. Both have PMs.
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8
Q

What is the function of cytoskeleton and what are the types?

A
  • Provides cell stability and movement
  • Types
    • Actin
    • Intermediate filaments
    • Microtubules
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9
Q

What are the three phases of polymerization for cytoskeleton?

What is dynamic instability?

How do kinesin and dynein play a role?

Name a disease associated with cytoskeleton.

A
  • 3 phases of polymerization
    • Nucleation: assembly of monomers
    • Elongation: rapid growth at (+) end
    • Steady-state: equal rate of polymerization and de-polymerization
  • Dynamic instability: rapid de-polymerization to cause separation of mitotic spindle.
  • Polymerization and de-polymerization occurs at (+) end and nucleation occurs at (-) end
    • Kinesin moves things to (+) end {cell surface is +}
    • Dynesin walks things back to (-) end {centrosome is -}
  • Disease: Hereditary Spherocytosis
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10
Q

Describe the function and properties of the cell membrane.

A
  • Expands with budding and fusion events
  • Impermeable to most ions and water molecules
  • Contains pumps and channels which allow movement of ions, molecules, and proteins
  • Glycoproteins on ECM interact with EC environment
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11
Q

Describe the properties and function of the nucleus. Name a disease associated with the nucleus.

A
  • Description: made up of nuclear envelope and nuclear pores
  • Function: storage of DNA
  • Disease: Hutchinson Gilford Progeria
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12
Q

Describe the properties and function of ribosomes.

What is the SRP’s role in ribosome function?

A
  • Description: cytosol and ER-bound organelles
  • Function: protein synthesis
  • SRP: signal recognition particle targets synthesized protein to ER
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13
Q

Describe the properties and function of the endoplasmic reticulum (ER).

A
  • Description: network of tubules that acts as the outer bilayer of the nuclear envelope
  • Function: processes proteins and lipid biosynthesis
    • Ca++ storage and detoxification
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14
Q

Describe the properties and function of the golgi apparatus. Name diseases often associated with the golgi.

A
  • Description: structure is dependent on microtubules with bi-directional transport from cis to trans-face
  • Function: supplies membrane and is site of glycosylation
  • Disease: congenital diseases associated with glycosylation such as seizures
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15
Q

Describe the properties and function of the lysosome. Name a disease associated with the lysosome.

A
  • Description: contains hydrolytic enzymes
  • Function: utilizes endocytosis (foreign macromolecules), macropinocytosis (fluid near PM), autophagy (cell components), and phagocytosis (foreign large particles/microorganisms)
  • Disease: Lysosomal Storage Disease
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16
Q

Describe the properties and function of the mitochondria. Name two types of diseases associated with the mitochondria.

A
  • Description: contains inner and outer membrane layers with own DNA
  • Function: generates ATP
  • Diseases
    • Lufts
    • Age-Related Degenerative Diseases (Parkinson’s and Alzheimer’s)
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17
Q

Describe the properties and function of the peroxisome. Name a disease associated with the peroxisome.

A
  • Description: single membrane with dense matrix
  • Function: oxidative reactions with hydrogen peroxide and FAs
  • Disease: Zellweger Syndrome Spectrum
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18
Q

Describe the properties and function of the cilia/flagella. Name a disease associated with the cilia/flagella.

A
  • Description: structural arrangement (9+2) of microtubules that extend from basal body
  • Function: lines tracts to move mucus and cause movement (sperm)
  • Disease: Dyskinesia (Kartagener’s Syndrome)
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19
Q

What is the general mechanism of direct transport between membrane enclosed organelles?

How are compartments in the cell diverse?

A
  • Vesicles bud from marked specific sites contain cargo proteins that are delivered to another membrane compartment by fusion.
  • Compartment diversity
    • Some require cytoskeletal elements to maintain shape
    • Small vesicles – diffusion, large vesicles – cytoskeleton tract
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20
Q

What are the types of trafficking pathways?

A
  • Types of trafficking pathways
    • Biosynthetic: secretory pathway from ER to golgi to PM
    • Endocytosis: PM to early/late endosomes to lysosomes
    • Retrieval: backflow of selected components is maintained
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21
Q

Where do clathrin coats, COP I coats, and COP II coats transport to and from?

A

Clathrin

  • Transport: PM to early endosomes and Golgi to lysosomes

COP I

  • Transport: Golgi to PM and Golgi to ER

COP II:

  • Transport: From ER to Golgi
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22
Q

What is the structure of clathrin coats?

A

made of triskelion (3 light, 3 heavy chains) that self assembles to a hexagonal structure

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23
Q

What is the assembly process of clathrin coats?

A
  • Arf-GEF recruits Arf-ADP → Arf-ATP → inserts into membrane → fatty acid tail exposure → clathrin recruitment → dynamin pinches off vesicle using accessory proteins and PIP2
  • Phorsphorylation of PIPs to PIP2s are also involved in recruitment
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24
Q

What is the disassembly process of clathrin coats?

A
  • Heat shock protein (Hsp70) is an ATPase stimulated by Auxilin → ATP hydrolyzes into ADP → Hsp70 uses energy from ATP hydrolysis to peel off coat
  • PIP2s are dephosphorylated to PIPs weakening coat-membrane interactions
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25
Q

What is the COP I assembly process?

A
  • Arf-GEF recruits Arf-ADP → Arf-ATP → inserts into membrane → fatty acid tail exposure → COPI recruitment → dynamin pinches off vesicle using accessory proteins and PIP2
  • Phorsphorylation of PIPs to PIP2s are also involved in recruitment
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26
Q

What is the COP I disassembly process?

A
  • Heat shock protein (Hsp70) is an ATPase stimulated by Auxilin → ATP hydrolyzes into ADP → Hsp70 uses energy from ATP hydrolysis to peel off coat
  • PIP2s are dephosphorylated to PIPs weakening coat-membrane interactions
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27
Q

What is the COP II assembly process?

A
  • Sar1-GEF recruits Sar1-GDP → Sar1-GTP → inserts into membrane → fatty acid tail exposure → COPII recruitment → dynamin pinches off vesicle using accessory proteins and PIP2
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28
Q

What is the COP II dissassebly process?

A
  • Heat shock protein (Hsp70) is an ATPase stimulated by Auxilin →ATP hydrolyzes into ADP →Hsp70 uses energy from ATP hydrolysis to peel off coat
  • PIP2s are dephosphorylated to PIPs weakening coat-membrane interactions
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29
Q

What is the function, structure of SNARE proteins, and the fusion process?

A
  • Function: acts as tethers to bring membranes together for fusion; this is a Ca++ dependent process
  • Structure
    • V-SNARE (transport vesicle made up of one polypeptide chain)
    • T-SNARE (target membrane made up of three polypeptide chains)
  • Fusion Process
    • T-SNARE traps V-SNARE
    • Energy from four helix bundle drives membrane fusion
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30
Q

What is the disassembly process of SNAREs?

A
  • NSF (i.e. NEM sensitive factor) and accessory proteins react with two cysteine residue to block activity
    • Hydrolyzes ATP to destabilize four-helix bundle
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31
Q

What is the function of RAB GTPases?

A
  • Function: molecular switches that control protein-protein interactions to allow for specific vesicle targeting
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32
Q

What is the process of RAB GTPases?

A
  • Rab-GEF (could be a SNARE or tether) recruits Rab-GDP on donor membrane → Rab-GTP → Rab-GTP inserts into donor membrane → transport vesicle/budding forms/occurs → Rab effector binds Rab-GTP → fusion → Rab-GDP
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33
Q

What are the effectors of Rab GTPases?

What is the idea of cooperative action for Rab GTPases?

A
  • Effectors
    • Motors, SNAREs, Tethers
  • Cooperative Activation
    • When subunits (ex: SNAREs and Rabs) work together
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34
Q

What is the process of protein exit from the ER and transport to and from the Golgi?

How does membrane thickness play a role?

A
  • ER exit sites to Golgi are with COPII; Golgi exit sites to ER are with COPI
  • Budding exit sites contain cargo receptors that bind to exit signals on cargo proteins (but are not necessary)
  • Membrane thickness (i.e. cholesterol) plays role in sorting transmembrane proteins
    • TM proteins in thick membranes goes to PM and TM proteins in thin membranes stays in ER and Golgi
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35
Q

What are ER resident proteins and how do they work?

A
  • ER Resident Proteins: marked by signal sequences on protein (i.e. KDEL or KKXX)
    • Return to ER through retrieval pathway
    • Affinity in ER Resident Receptors
      • More acidic pH in Golgi increases affinity of receptor for ER resident proteins
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36
Q

How do chaperone proteins work and provide an example?

A
  • Chaperone Proteins: fold proteins and keep misfolded proteins from leaving ER
    • Example: BiP act as chaperones for ABs (but also think of CFTR protein)
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37
Q

Where does glycosylation occur and what are the two main types?

A
  • Glycosylation occurs in Golgi
    • Golgi more prominent in cells that secrete large amounts of glycoproteins (i.e. goblet cells in small intestine)
  • Features
    • N-linked glycosylation: sugar attached to asparagine reside
    • O-linked glycosylation: sugar attached to serine or threonine residue
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38
Q

What is the importance of glycosylation?

A
  • Importance
    • Prevents approach of proteases
    • Prevent aggregation
    • Promotes cell signaling
    • Transport – M6P is linked to lysosomal hydrolases to target to lysosome
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39
Q

What is the transport mechanism for lysosomal hydrolase?

A
  • Acid hydrolases are only active at low pH
    • Vacuole ATPase pumps H+ against gradient into lysosome
  • M6P is used to tag lysosomal hydrolase precursors from ER in the Golgi
  • M6P binds to M6P receptor in Golgi → early endosome → lysosome through Clathrin
  • Addition of GlcNAc-P to M6P in the early endosome to release hydrolase precursor
  • M6P receptor is recycled back to Golgi
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40
Q

What are the features of phagocytes?
What types of professional phagocytes?

What is the ingestion process of phagocytes?

A

Phagocytosis

  • Greater than 250nm diameter
  • Professional phagocytes (components of WBCs)
    • Macrophages: apoptotic cells
    • Neutrophils: foreign organisms
  • Ingestion Process
    • Attachment (through tagging) → Engulfment (formation of phagocytotic cup through the use of GTPase-dependent actin protrusions) → Fusion with Lysosome (degradation)
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41
Q

What is pinocytosis?

A
  • Ingestion of fluids
  • Less than 100nm diameter
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42
Q

What is receptor-mediated endocytosis and give the process using LDL particles?

A
  • Clathrin mediated
  • Example: LDL particles
    • LDL receptors on ECM of PM recognize LDL particle
    • LDL receptor binds adaptor protein and clathrin coat assembles
    • Transported to early endosomes then lysosomes
    • LDL receptor dissociates from LDL particle in early endosome and receptor is recycled back to PM
    • Free cholesterol enters cytoplasm
    • Promotes homeostasis by inhibiting LDL receptors and shutting down cholesterol synthesis when [LDL]cell is high
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43
Q

What is transcytosis used for and provide an example of where it would be used?

A
  • Used in polarized epithelial cells to transfer macromolecules from one extracellular space to another (apical to basolateral)
    • Example: transferring of ABs from mother’s blood to baby’s blood
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44
Q

What are the two types or regulated pathways and provide examples of where each would be used?

A
  • Signal Mediated Diversion to Lysosomes
    • M6P receptor example
  • Signal Mediated Diversion to Secretory Vesicles
    • Occurs in specialized cells for the release of neurotransmitters and hormones
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45
Q

What is the constitutive pathway and how does it work?

A
  • Constitutive Pathway
    • Does not have any signals to mediate pathway
    • All vesicles are destined for PM
    • Mature secretory vesicles can selectively aggregate in trans-Golgi, but aggregation signal is unknown
46
Q

What’s the hierarchy of protein structures?

A
  • Primary
    • Amino acid sequence, location of disulfide bonds, covalent structure of the protein
  • Secondary
    • Alpha helices, beta sheets, turns
  • Tertiary
    • Includes position of AA side chains
    • Includes interactions between secondary structures and folding arrangement of the various domains
  • Quaternary
    • Combination of two or more polypeptide chains to form complete unit
47
Q

What are the properties of amino acids and what are the amino acids under each property?

A

Non-Polar AAs

  • GAVLIMP WF – “GAVin LIMPed with Warm Fingers”
    • Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Proline, Tryptophan, Phenylalanine

Polar

  • STCYNQ – “SomeTimes Cats Yell Not Quietly”
    • Serine, Threonine, Cysteine, Tyrosine, Asparagine, Glutamine

Charged

  • DEKRH – “Dumb Evil Kings Rule Hell”
    • Aspartate, Glutamate, Lysine, Arginine, Histidine
48
Q

Describe the peptide bond and the restrictions it puts on protein structures.

A
  • Partial double bond character (planar) because of resonance of electrons between carbonyl oxygen, carbonyl carbon and the nitrogen
  • Peptide bond is rigid with no freedom of rotation, but rotation is allowed around bonds of the alpha-carbon
    • Nitrogen—alpha-carbon bond is called phi
    • Carbonyl—alpha-carbon bond is called psi
49
Q

How does the Ramachandran Plot work?

A
  • Uses Van der Waals’ radii and bond length to determine which bond angles result in appropriate energies
  • More colored area of the plot means more flexibility of bond
50
Q

What are the differences between Glycine and Proline and how do they act in terms of providing flexibility/rigidity in proteins?

A
  • Glycine and Proline are different because glycine only has a hydrogen as side-chain, allowing for extreme flexibility
  • Proline cannot form any hydrogen bonds, so it is the most limited in flexibility
51
Q

What are the secondary structures in proteins and what are their properties?

A
  • Alpha-Helix
    • Right-handed, 3.6 AAs per turn, i to i+4 parallel hydrogen bonds maximizes local structure
    • Compact packing of backbone, with no hole down the middle and side chains facing outwards
  • Beta-Sheets
    • Hydrogen-bonds are interstrand and perpendicular to the long axis of the chain
    • Beta-branched AAs (V, I, and T) fit better in sheets than in helices
    • Sheets stack on each other
    • Sheets are more flexible than helices
52
Q

Compare and contrast transmembrane protein sequences and cytosolic protein sequences?

A
  • Transmembrane protein sequence
    • Twenty nonpolar AAs in an alpha-helix are needed to span the lipid bilayer (multi-pass proteins require one side of each helix to be non-polar)
  • Cytosolic protein sequence
    • Hydrophobic inside, hydrophilic outside
53
Q

What is the role of hydrogen bonds in the folding process in proteins?

A
  • Hydrogen bonds
    • Dipole-dipole interaction
    • H-bonds must be nearly linear to maximize energy of stabilization (remember: alpha helix and beta sheets)
    • Forms extensive network of H-bonds in protein backbone
54
Q

What is the role of hydrophobicity in the folding process of proteins?

A
  • Hydrophobicity
    • Water prefers to interact with itself over hydrophobic groups, allowing for minimal exposure of hydrophobic groups
    • Spherical protein shapes only expected if only hydrophobicity drives protein structure
55
Q

What is the role of configurational entropy in protein folding?

A
  • Configurational entropy
    • There is great entropic cost (requires energy) to fixing orientation angles of backbone and sidechains to a single unique value
    • Instead of just being random, the native conformation must overcome significant barriers to formation
56
Q

What’s the importance of amino acid sequences not being able to fold by themselves?

A
  • These amino acid sequences only become structured in the presence of other compounds, (other proteins or ligands).
  • As such, these sequences are critically important to regulation of a protein’s activity, and activation or suppression of signaling pathways.
  • These sequences are the most frequent sites of post-translational modification, and provide easily accessible conformations that can bind to other proteins for signaling cellular conditions.
57
Q

Describe the forces that allow proteins to bind to ligands?

A
  • The interior is shielded so the protons only go where they are supposed to, not toward the water
  • There are electrostatic interactions, hydrophobic interactions, and hydrogen bonds on the interior caused by AA residues in the active site
  • Everything is close and complementary in shape and polarity
58
Q

Describe the equlibirum binding curve and the role of Kd.

A
  • Kd is the concentration of ligand at ½ maximal saturation
59
Q

Describe how allostery works in ligand binding.

Define positive/negative cooperativity. Provide an example.

A
  • Ligand binding at one site can influence binding of a second ligand at another site
    • Positive cooperativity is when binding of the first ligand increases affinity for the second ligand
    • Negative cooperativity is when the binding of the first ligand decreases the affinity for the second ligand
    • The second ligand can be the same or different molecule from first
  • Example: myoglobin versus hemoglobin
60
Q

What effect do increases and decreases in pH, DPG, and temperature have on oxygen binding curves?

A
61
Q

Describe how enzymes work and the thermodynamics of the process.

A
  • Enzymes lower the transition state barrier to help proteins reach their native conformation much faster
  • Highest affinity for enzyme is when protein is in transition state conformation
  • An exergonic reaction can be coupled with an endergonic reaction to make the process spontaneous overall (negative change in G)
62
Q

What are two types of effects of enzyme specificity?

What are two theories of enzyme interaction?

A
  • Proximity effect – bringing two substrates close
  • Orientation effect – orientation of substrate with respect to active site side chains
  • Theories: lock and key model and induced fit model
63
Q

How do Acid-Base catalysis help enzymatic reactions?

A
  • Acid-Base Catalysis
    • Transition state may require the loss or gain of a proton on the substrate
    • Active sites frequently have an acid or base residue at the active site to contribute to binding and catalysis
      • Histidine is especially popular because it can donate a proton on one side and accept a proton on another
64
Q

How does covalent catalysis help enzymatic reactions?

A
  • Transient formation of a covalent bond between the enzyme (or cofactor) and the substrate
65
Q

How does metal ion catalysis help enzymatic reactions?

A
  • Ions bind to substrates to orient them properly for reaction
  • Mediates redox reactions by utilizing metal ion’s ability to lose and gain electrons
  • Can neutralize the charge
66
Q

What is the Michaelis-Menton Equation and what is KM?

What does a high/low KM indicate?

A
  • KM is the measure of dissociation/affinity of the ES complex
  • KM= ES breaking apart/ ES staying together
    • High KM means the ES is breaking apart, and has low affinity
    • Low KM means denominator is larger, meaning ES staying together and has high affinity
  • KM is typically regarded as ½ the VMAX or the maximum rate a reaction of the substrate using its enzyme can occur
67
Q

What is a competitive inhibitor and how does the lineweaver-burk plot look like?

A
  • Competitive
    • Competes with substrate at active site to bind enzyme
    • Inhibitors have structures similar to the substrate or product
68
Q

What is non-competitive inhibition and what is the lineweaver burk plot for it?

A
  • Inhibitors bind to free E and ES at same affinity
  • Can also be called a “mixed” inhibitor as it is both a competitive and non-competitive inhibitor
69
Q

What is uncompetitive inhibition and what is the lineweaver burk plot for it?

A
  • Uncompetitive
    • Inhibitors bind only to the ES complex and block product formation
    • Increase substrate affinity
70
Q

Relate enzyme inhibition/activation in relation to drug mechanism Allostery, Enzyme Inhibition, and Drugs

A
  • Allosteric enzymes are found in the most carefully regulated steps in metabolism
  • These are good targets for therapeutics because they already have sites on enzyme to regulate activity
  • Drugs are not competitive for the active site but binds to allosteric molecule site, thus having less side affects
71
Q

Describe irreversible inhibition.

A
  • Irreversible inhibitors bind to the active site, deeming the active site non-functional
  • Only way to restore is by synthesizing new enzyme
72
Q

Describe transition-state inhibitors and why they are so effective.

A
  • Compounds have chemistry similar to the transition state rather than to substrate or product.
  • Slow enzyme conformation change and extremely tight, effective irreversible binding
73
Q

What is the function of chaperones in the folding process and what are some types?

A
  • Prevent inappropriate association/aggregation/misfolding by binding and supporting
  • Some couple ATP hydrolysis to unfold non-native structures
  • Chaperone concentration greatly increases with stress response to help fold greater number of proteins being synthesized
  • Types: box chaperones, prolyl-peptide isomerases, and disulfide isomerase enzymes
74
Q

Describe how amyloid fibrils form in protein folding diseases. What are the two types that were discussed?

A
  • The amyloid itself is toxic where ever it accumulates.
  • In AL, the many different light chains of an AB are misfolded and aggregate together to form amyloid fibrils.
  • Familial transthyretin amyloidosis is caused by misfolded transthyretin monomers that denature and aggregate into amyloid.
  • Mechanistically, the growth of the amyloid fibril can break cell membranes and kill cells due to its rigid “cross-bridge structure”.
75
Q

What are the three steps of translation and what occurs at each step?

A
  • This is a highly regulated process
  • Initiation: Methionine (only one codon codes for M) attaches to initiator tRNA
  • Elongation: AAs are added in the peptidyl transfer center
    • A-site and P-site scrutinize codon-anticodon interactions to ensure correct AA is added; 3rd position has less fidelity/wobble position
    • Deacylated tRNA is translocated from P-site to E-site, where it finally dissociates
  • Termination: stop codon indicates end of polypeptide synthesis
76
Q

What do aminoglycosides do near the A-site during translation?

A
  • Aminoglycosides near A-site on the ribosome decreasing fidelity, so wrong amino acids end up being incorporated much more often, producing nonfunctional proteins
77
Q

What are the two types of mutations and what are the nature of both?

A
  • Conservative mutations code for AAs with similar properties as the wild type.
    • Because mutations in the third nucleotide position in the codon (wobble position) can code for the same AA, the protein sequence does not change.
    • Sometimes a deletion of a codon
  • Non-conservative mutations code for AAs that have differing properties
    • Frameshift or truncation mutations
78
Q

What is the nature of post-translational modifications and their role in protein function?

Provide an example that demonstrates the importance of post-translational modifications.

A
  • Modulates – alters the the activity of a protein
  • Adds – incorporates non-protein functional groups to protein structure (i.e. heme centers in hemoglobin)
  • Recruits – recruits other proteins into complex
  • Targets – routes protein molecules to a specific cellular location
  • Example: insulin receptor
    • Phosphorylation of tyrosine residue on tyrosine kinase receptor opens up active site allowing ATP binding
79
Q

How does ubiquitin regulated protein degradation work?

A
  • Ubiquitin can be added to lysine residues in proteins
  • Only when a polyubiquitin chain (single ubiquitin added at a time) is present can the protein recognized for degradation
    • Monoubiquitin used for transport or signaling
  • Labeled protein targeted to proteasome
80
Q

What are the functions of the parasympthetic nervous system?

A
  • Normal homeostasis
  • Slows things down
  • Rest and digest
  • Can control specific things
  • Body cavities and head
81
Q

What does the parasympathetic nervous system act on?

A
  • Cardiac muscle
  • Smooth muscle
  • Organs/salivary glands
  • Does not act on blood vessels
82
Q

Where does the parasympathetic originate from?

A

Cranio-sacral region (brainstem and coccyx)

83
Q

Describe the neuron anatomy of the parasympathetic ganglia.

A
  • Long preganglionic neuron
  • Short postganglionic neuron near the organ
84
Q

What is the preganglionic receptor and its transmitter in the parasympathetic nervous system?

What are the agonists and antagonists?

A
  • Nicotinic (ACh) [NN]
  • Agonist: nicotine
  • Antagonist: curare
85
Q

Describe the receptor structure and ion channel associated with preganglionic parasympathetic nervous system?

A
  • Nicotinic (ACh) [NN]
  • Ligand gated sodium channels composed of 5 subunits surrounding the sodium channel
  • Binds to receptor on two of the subunits, activating channel to allow Na+ to rush in and cause depolarization
86
Q

What are the functions of the sympathetic nervous system?

A
  • Stress management
  • Speeds things up and drives the autonomic system forward
  • Fight or flight
  • System fire alarm
  • Entire body
87
Q

What does the sympathetic nervous system act on?

A
  • Cardiac muscle
  • Smooth muscle
  • Organs/adrenal medulla
  • Arteries
  • Sweat glands
88
Q

Where does the sympathetic originate from?

A

Thoraco-lumbar area of the spine

89
Q

Describe the neuron anatomy of the sympathetic ganglia.

A
  • Short preganglionic neuron with synapse paravertebrally
  • Long postganglionic neuron to the organ
90
Q

What is the preganglionic receptor and its transmitter in the sympathetic nervous system?

What are the agonists and antagonists?

A
  • Nicotinic (ACh) [NN]
  • Agonist: nicotine
  • Antagonist: curare
91
Q

What does the adrenal sympathetic act on?

A

Adrenal Medulla

92
Q

What does the somatic nervous system act on?

A

Skeletal muscle

93
Q

What is the preganglionic receptor and its transmitter in the somatic nervous system?

What are the agonists and antagonists?

A
  • Nicotinic (ACh) [NM]
  • Agonist: nicotine
  • Antagonist: curare
94
Q

Describe the receptor structure and ion channel associated with the preganglionic strucure in the sympathetic nervous system.

A
  • Nicotinic (ACh) [NN]
  • Ligand gated sodium channels composed of 5 subunits surrounding the sodium channel
  • Binds to receptor on two of the subunits, activating channel to allow Na+ to rush in and cause depolarization
95
Q

Describe the receptor structure and ion channel associated with the preganglionic neuron in the somatic nervous system?

A
  • Nicotinic (ACh) [NM]
  • Ligand gated sodium channels composed of 5 subunits surrounding the sodium channel
  • Binds to receptor on two of the subunits, activating channel to allow Na+ to rush in and cause depolarization
96
Q

Which nervous system utilizes muscarinic receptors for its postganglionic neurons?

A

Parasympathetic

97
Q

Describe the structure of the muscarinic receptor.

A

7-Transmembrane G-Protein Coupled Receptor: span membrane 7 times with GPCR that facilitates intracellular secondary messaging

98
Q

How do the odd muscarinic receptors act and how many subtype receptors are there?

A
  • M1, M3, M5
  • Gq is the alpha subunit of the G protein
  • Activation results in stimulation of PIP2 hydrolysis – increasing Phospholipase C and increasing DAG (which increases Ca2+) - increasing PKC
  • Muscle contraction (i.e. persistalsis)
99
Q

How do the even muscarinic receptors act and how many subtypes are there?

A
  • M2, M4
  • Only act on the heart
  • Gi is the G protein
  • activation results in inhibition of adenylyl cyclase through Gi, which enhances K+ conductance flow from inside to outside the cell down the gradient to hyperpolarize the cell
  • May also decrease Ca2+ influx through Gi closing Ca2+ channels and decreasing the release of transmitter
100
Q

What is the agonist and antagonist to muscarinic receptors?

A
  • Agonist: muscarine
  • Antagonist: atropine
101
Q

What are the steps in the synthesis of epinephrine?

A

Tyrosine → L-Dopa → Dopamine → Norepinephrine → Epinephrine

102
Q

What neurotransmitter do sweat glands, adrenal medulla, and adernergic receptors use?

A
  • Sweat Glands: ACh
  • Adrenal Medulla: Epi
  • Adernergic: Norepi
103
Q

How is epinephrine or norepinephrine terminated in the synapse?

A
  • Reuptake
    • ​Alpha2 (an autoreceptor) senses concentration and signals for reuptake
  • Diffusion
  • Metabolism
104
Q

What are the agonists and antagonists to adernergic receptors?

A
  • Agonists: NE, EPI
  • Antagonists: Proponolol (B1/B2 nonspecific blocker)
105
Q

What are the functions of alpha1 receptors and where do they act on?

A

Functions

  • Gq pathway
  • Increases Intracellular Ca2+
  • Vasoconstriction (BP­) increases

Acts On

  • On smooth muscle of vessels, eye, and GI/urinary sphincters
  • smooth muscle contraction by stimulating phospholipase C and Ca2+
106
Q

What are the functions of alpha2 receptors and where do they act on?

A

Functions

  • Gi
  • Decreases cAMP (through adenyl cyclase)
  • Decreases norepinephrine release (autoreceptor) by hyperpolarizing the cell

Acts On

  • Presynaptic nerve terminals
107
Q

What are the functions of beta1 receptors and where do they act on?

A

Function

  • Gs
  • Increases HR
  • Increases contractility

Acts On

  • Heart
108
Q

What are the functions of beta2 receptors and where do they act on?

A

Function

  • Gs
  • coupled to Gproteins → increases adenylyl cyclase and cAMP → phosphorylation of myosin light chain kinase → blocks function and decreases contraction

Acts On

  • located on most tissues (can be innervated or noninnervated)
  • Activation leads to relaxation of smooth muscle (uterus, GI, bladder)
109
Q

What are the functions of beta3 receptors and where do they act on?

A

Function

  • Gs
  • increases lipolysis

Acts On

  • adipocytes
110
Q

How is acetyl cholinesterase broken down?

A
  • Serine attaches to the ester site → breaks down into acetate and acetylcholinesterase
111
Q

What is the therapeutic function of acetyl cholinesterase inhibiton? Name a disease associated with the neuromuscular junction.

A
  • Therapeutically, acetyl cholinesterase inhibition allows for ACh to remain in synapse to stimulate receptors
  • Conversely, lack of acetyl cholinesterase can cause overstimulation of ACh (insecticides and WMDs target acetyl cholinesterase)
  • Myasthenia Gravis: lack of ACh postsynaptic receptors causes a reduction in depolarization and therefore muscle weakness
112
Q

What is meant by the natural tension between innervated and non-innervated receptors and the potential therapeutic use(s) of that tension?

A

Since there are more beta 2 receptors than innervated alpha 1 receptors (vasoconstriction) in non-innervated tissues like the smooth muscle of blood vessels, epinephrine release into blood stream will cause vasodialation.

SPM (17 decks)

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