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143 Cards in this Set
- Front
- Back
lipids include many types of what?
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molecules
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Rather than lipids being defined by a ? they are defined by a ?.
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not by structure but by property
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Name 3 molecules defined by structure?
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proteins, carbs, nucleic acids
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The property which defines a lipid?
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they are largely insoluble in water, but relatively soluble in hydrophobic (organic) solvents
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The two options for lipids?
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either totally hydrophobic or amphiphilic (having both hydrophobic and hydrophilic parts)
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Fatty acids are aka what?
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storage lipids
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What can lipids store?
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energy (fat and oils)
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Many lipids contain ? acids.
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fatty
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Is the fatty acid the sole component of the lipid?
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it may be...or it may be linked to another entity by an ESTER or AMIDE bond.
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The 2 melting point trends?
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1. the longer the carbon chain, the higher the m.p.
2. dbl bds introduce kinks in chains...disrupt the association of adjacent chains...and so decrease the m.p. (b/c groups of molecules are less likely to associate to from solids)...and the more dbl bds (up to a pt.) the lower the m.p. |
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So longer Carbon chains do what to mp?
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increase it
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So dbl bds do what to mp?
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decrease it (to a pt)
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How do you know according to table 10-1 when a FA is hydrophobic?
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it is more soluble in benzene than H2O
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Storage lipids : ? and ? : contain ?.
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storage lipids : fats and oils: contain fatty acids
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Larger molecules have ? mp and ? solubilites?
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higher mp...lower sol.
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A saturated fatty acid has no what?
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dbl bonds
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1 Dbl bond is aka what?
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mono-unsaturated
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2 or more dbl bds is aka what?
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poly-unsaturated
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Saturated fatty acids are generally what at room temp?
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(no dbl bds)
generally solids at room temp (and body temp) |
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Unsaturated FAs are generally what at room temp?
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(dbl bonds)
generally liquid at room temp (and body temp) |
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Which has the higher melting point sat. FAs or unsat. FAs?
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saturated FAs (remember they are solid at room temp)
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If two FA molecules had 16 carbons but only one had a dbl bd which one would have a higher melting point?
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the saturated one with no dbl bds would have a higher mp
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So increaed #C = an increase what?
But an increased dbl bd = what? |
more Cs gives a higher mp BUT more dbl bds give a lower mp
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What is reqd for transport of FAs?
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serum albumin
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Most FAs exist in our body as what?
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esters
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FAs are often incorporated into what?
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triaglycerols (includes, triglycerides, fats, TAG's)
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In vertebrates, what stores large amts of TAGs?
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adipocytes
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Triaglycerols = ? = ? = ?
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triaglycerols = triglycerides = fats = glycerol + 3 FAs (simple and mixed)
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Some advantages of storing in lipids (TAGs) instead of polysacchs?
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1. C atoms are highly reduced...this means that the energy density is 2X what it is in polysacchs
2. hydrophobic mol.s so not hydrated (no xtra water weight) (so you can carry energy in a more small, efficient area) 3. insulate against cold |
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Which fats are healthier for you?
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unsaturated (dbl bds)(liq at room temp)
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Kearney's review sheet says triaglycerol's has ? density?
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low
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What is stored in adipocytes?
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triaglycerols = triglycerides = fats = glycerol + 3 FAs
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Advantages to storing energy in lipids?
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1. C atoms are highly reduced...high energy-density
2. no h2o of hydration for these hydrophobic molecules...lighter cells 3. insulation |
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Fats in foods are generally mixtures of what?
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different triaglycerols with various FAs
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Describe composition of vegetable oil?
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high percentage of unsat. FAs...liquids
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Describe composition of Animal fats?
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higher percentage of saturated FAs...solids
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The two components of waxes?
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FAs + alcohol (so esters and long chain alcohols)
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The melting point of waxes is generally what?
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fairly high (60-100C)...solid at room temp
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Are waxes solid, liquid or vary?
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solid
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Why are biological waxes important for the wings of birds and insects?
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they are water repellant
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Why are bio waxes important for leaves?
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they prevent evaporation/dehydration
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What do bio. waxes protect plants and animals from?
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parasites
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Name three things that waxes are used in?
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lotions, ointments, and polishes
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Structural lipids are aka?
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membrane lipids
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2 types of structural (membrane) lipids?
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A. glycerophospholipids
B. Sphingolipids |
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Describe structure of glycerophospholipids?
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A. glycerol backbone
B. with phosphate C. 2 FAs + 1 polar group |
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Describe structure of sphingolipids?
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A. sphingosine backbone
B. with or without phosphate C. 1 FA + 1 polar group |
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What do sphingolipids define?
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the human blood groups (A,B,O,)
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Membrane lipids are continually what?
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degraded and replaced, this is carried out by enzymes in lysozomes (which breakdown lipids)
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What genetic diseases are caused by defects in the enzymes that degrade and replace membrane lipids...what do they lead to?
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-lead to an accumulation of lipids (cuz can't breakdown)
1. Niemann-pick 2. Tay Sachs 3. Gaucher's 4. Fabry's 5. Sandhoff's |
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Describe structure of sterols? (you are going to need to know this visually)
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4 fused rings
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Where are sterols found?
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in membranes of eukaryotes but not not prokaryotes (bacteria)
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What are the precursors to sterols?
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isoprene...(synthesized from isoprene/isoprenoids)
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What is the major sterol in animal tissue?
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cholesterol...an amphipathic (polar end and nonpolar end)
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Sterols are what overall?
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amphipathic
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Besides structural and storage lipids name 3 other functions of lipids?
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1. signals
2. cofactors 3. pigments |
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Describe lipids as pigments?
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they absorb light...capture energy and give color...usually have conjugated dbl bds)
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The 3 levels of lipids as signals?
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1. Phosphatidylinositol (key)
2. Eicosanoids 3. Steroids |
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Phosphatidylinositol is what kind of lipid signal?
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intracellular signal
-it and it's deriv.s regulate cell structure and metabolism |
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Eicosanoids are what kind of lipid signals?
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(paracrine hormones)
-act on neighbor cells (have 20 carbons in molecule) -so "nearby intercellular signals" |
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Name 3 paracrine hormones that are eicosanoids?
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(20 C FA derivs)(act on cells near site of synthesis)
1. prostaglandins 2. thrombaxones 3. leukotriene |
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What are eicosanoids derived from?
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arachidonic acid
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What do the prostaglandin (eicosanoid lipid signal) do?
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regulatory molecules...fever, pain, inflammation
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What do the thromboxanes (eicosanoid lipid signal) do?
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produced by platelets...act in clot formation
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What do the leukotriene (eicosanoid lipid signal) do?
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first found in leukocytes...role in asthma
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Steroids are aka what?
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oxidized derivatives of sterols
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Difference between sterols and steroids in structure?
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hydrophobic side chain of sterols replaced by a more polar group...sometimes an addnal polar group...polar groups make molecules easier to transport in aqueous environ.s (ex. blood)
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Where are steroids observed?
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1. sex hormones (testosterone, estradiol)
2. Adrenal cortex hormones (cortisol) 3. anti-inflammatory drugs |
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What are vitamins?
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precursors of hormones, cofactors, light absorbers,etc.
-essential for vertebrates but not synthesized by them (except vit D) |
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Which category of vitamins are we concerned with?
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fat-soluble (ADEK)
-soluble in nonpolar solvents |
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Where are the fat-sol. vitamins derived from?
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from isoprene/isoprenoids (like cholesterol)
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5 aspects of vitamin D?
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1. transformed into a hormone important for Ca2+ uptake
2. precursor transformed into D3 by light (in the skin...light reqd) 3. liver and kidney reqd for full activation 4. absence leads to bone defects and rickets 5. found in milk and butter (D2 not D3) |
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5 aspects of vitamin A?
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1. hormone and visual pigment
2. important for skin development 3. synthesis : precursor beta carotene>retinol>retinal(eyes, visual pigment)>retinoic acid(epithelial, skin cells) 4. found in milk, butter, etc 5. beta carotene (precursor) is found in yellow veggies (carrots) and dark green veggies |
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What can a vit A deficiency lead to?
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dry skin, eyes, slow dev and growth, night blindness
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How is vit E important?
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an important anti-oxidant
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What is an anti-oxidant?
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ring in vit E destroys oxygen radicals
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How is vit K important?
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for promotion of blood clotting and as rat poison
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How is warfarin related to vit K?
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warfarin is an anticoagulant...and a derivative of vitamin K
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How does vit K work as a rat poison?
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causes them to bleed to death
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What are the 4 general principles of biosignaling?
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1. specificity
2. sensitivity 3. modification 4. integration |
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Describe specificity of biosignaling?
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signal molecules fits binding site on its complementary receptor...other signals do not fit...specific
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Describe sensitivity of biosignaling?
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high receptor-signal affinity...cooperativity...and amplification
-a small amt of ligand (signal) leads to the occupation of a large fraction of the receptors binding sites -cooperativity...like hemoglobin...them that has gets |
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Describe modification of sensitivity of biosignaling?
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-Desensitization/Adaptation
-receptor activation triggers a feedback circuit that shuts off the receptor or removes it from the cell surface |
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Describe integration of multiple signals of biosignaling?
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when 2 signals have oppo effects on a metabolic characteristic such as the [conc] of a 2nd messenger X, or the membrane potential Vm, the regulatory outcome results from the integrated input from both receptors
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Describe the typical concentrations of a gated ion channel?
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intracellular = higher K+
extracellular = higher Na+, Ca2+, Cl- |
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What is unique about intracellular Ca2+?
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only one with <1mM (so a small change can be relatively large)
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What is a gradient involved in?
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active transport
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How is a gradient created?
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Na+K+ATPase (3 Na+ pumped out for every 2 K+ pumped in, creating an electrochemical gradient)
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The gradient created by Na+K+ATPase can do what?
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drive the passive transport, thru gated channels, of Na+ and Ca2+ to move into the cell, and K+ and Cl- out
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Where is the nicotinic acetylcholine receptor located?
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postsynaptic membrane
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What does the nicotinic acetylcholine receptor open in response to?
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to the binding of acetylcholine or nicotine
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What does the nicotinic acetylcholine receptor allow to move into the cell?
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allows Na+ and Ca2+ to move into the cell...depolarizing the membrane gradient
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Describe structure of nicotinic acetylcholine receptor?
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5 subunits each with 4 transmembrane helices
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When is nicotinic acetylcholine receptor closed? Open?
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closed when hydrophobic AAs line the central canal
open when subunits rotate so that polar residues line the channel |
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In the nicotinic acetylcholine receptor when does desensitization result?
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if acetylcholine is not degraded
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What opens the voltage-gated Na+ channel?
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depolarization
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What happens when the voltage-gated Na+ channel opens?
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allows more Na+ ions to move into the cell...which results in further depolarization
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Describe structure of voltage gated Na+ ion channel?
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4 domain polypeptide, each with 6 transmembrane helices
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What happens in response to depolarization in the voltage-gated Na+ ion channel?
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helices move relative to each other, opening the central channel, allowing passage of Na+ ions
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What opens the voltage-gated Ca2+ channels?
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depolarization
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What is allowed when the volt-gated Ca2+ channel opens?
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allows Ca2+ to move into the cell
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When Ca2+ enters into the cell what does it do?
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triggers the release of acetylcholine to pass to next neuron
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What happens to the Na+ channel when transmembrane pot. changes?
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opens up and Na+ ions can pass thru
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What causes volt-gated K+ channels to open?
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depolarization
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What does the opening of the volt-gated K+ channels do?
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allows K+ to move OUT of the cell (the other channels allow movement in)
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Structure of K+ channel?
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4 subunits with 4 helices
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Where do the K+ ions pass thru?
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channel thru the center of the volt-gated K+ ion channel
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Describe receptor enzymes?
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ligand binds to extracellular binding site, triggering enzyme activity in the cytosol
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What is a protein kinase? give and example
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A receptor enzyme (ex. insulin receptor)
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Describe structure of protein kinase (insulin receptor)?
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1. 2 extracellular alpha chains include insulin binding sites
2. 2 transmembrane beta subunits have kinase activity on intracellular side of membrane |
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Insulin binding on the protein kinase (insulin receptor) initiates what?
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conformational change...which leads to beta subunits autophosphorylation
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After the conformation change in the protein kinase (insulin receptor) and beta subunit autophosphorylation what occurs?
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the phosphorylated/activated enzyme phosphorylates IRS-1 (target protein)
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What is IRS-1 aka?
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insulin receptor substrate
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Once phosphorylated what does IRS-1 begin? (7)
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a chain rxn that leads
1. activation of RAF 2. phosphorylation of MEK 3. Phosphorylation of ERK 4. movement of ERK into nucleus 5. activation of genes (gene expression) 6. synthesis of new proteins 7. cell division |
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Besides the chain rxn what else does IRS-1 cause?
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metabolic changes
1. inactivation of GSK3, leading to activation of glycogen synthase, leading to the synthesis of glycogen from glucose 2. mvmt of glucose transporter GLUT4 from 'storage' (vesicles) to the cell surface, leading to the transport of more glucose into the cell, reducing the blood glucose concentration |
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What is Guanylyl Cylase?
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another type of receptor enzyme...synthesizes cGMP
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When is cGMP synthesized?
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When the ligand is bound on the extracellular surface, cGMP is synthesized inside the cell
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2 examples of guanylase cylase receptors?
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1. ANF receptor
2. Guanylin and Endotoxin Receptor |
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What is ANF released by?
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stretched heart...goes to kidneys
(from heart>kidney>muscle) |
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What does the release of ANF lead to? (2)
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1. rise in [cGMP], triggering release of Na+ and H2O, reducing blood volume
2. bounds to receptors in smooth muscles, leads to the relaxation of smooth muscle, allowing blood vessels to expand, decreasing blood pressure |
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What activates the Guanylin and endotoxin receptors?
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activated by intestinal chloride secretion (guanylin)(elevates cGMP, which increases Cl- secretion in the intestine and modifies the retention of H2O)
also by an endotoxin produced by gram-negative bacteria (such as E coli)(leads to excess Cl- secretion, producing diarrhea) |
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Give an example of a soluble guanylyl cylase?
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nitric oxide-activated GC
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What does a soluble GC (guanylyl cylase) increase?
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[cGMP]...so for an example an increased [NO] will increase [cGMP] thru synthesis
-reduces the forcefulness of heart contractions in response to NO or nitroglycerin -so nitro can be used to tx angina |
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An indirectly acting receptor protein?
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G Protein-Coupled Receptors
(GPCRs) |
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The 3 components of the G protein-coupled receptors (GPCR)?
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1. plasma membrane receptor
2. guanosine nucleotide-binding protein (aka G protein) 3. in-membrane enzyme that generates an intracellular second messenger (ex. cAMP) |
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How many GPCRs are there and what do the transduce?
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more than a 1000 and they transduce messages such as light, smells, taste, hormones, etc.
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What do more than half of all medicines prescribed today target?
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a GPCR
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Give an example of a typical GPCR receptor?
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Beta adrenergic receptors (BAR)....the prototype
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Describe structure of beta adrenergic receptor (BAR)?
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integral membrane protein with 7 hydrophobic transmembrane helices that weave back and forth across the membrane, with an extracellular epinephrine binding site
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The ? protein is associated with the beta adrenergic receptor?
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G protein (guanosine nucleotide binding protein)
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The G protein assoc. with the beta adrenergic receptor is what?
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stimulatory (Gs)
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How is the G protein activated?
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when epinephrine binds to the receptor, GDP is released and GTP is bound, thus activating the G protein
(so GDP before and replaced by GTP after) |
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When the G-protein is activated what subunit seperates and where does it go?
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the alpha subunit of Gs(Gsa) seperates from the beta and theta subunits and moves to adenylyl cyclase (AC) and activates it, so that it catalyzes the synthesis of cAMP
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After activating Adenylyl cylase (AC) what does the Gsa (alpha subunit of the G protein) do?
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it inactivates itself by converting its bound GTP to GDP
(so back to GDP) ...then the Gsa dissociates from the AC, and reassociates with its beta and theta subunits and is ready to go again (Gs) |
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The cAMP synthesized by the AC and alpha subunit can do what once the alpha subunit has dissociated?
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activates protein kinase A (PKA)...which then goes on to phosphorylate many cellular proteins
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The process of the indirectly acting receptor proteins, G proteins, GPCRs, ACs, Gs, Gsa, cAMP, etc is a good example of what?
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signal amplification
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The epinephrine cascade was described in the last few notecards...what is it a good example of?
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amplification
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cAMP is usually ? but ? can increase it's ?.
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cAMP is usually degraded but methyl xanthines (caffeine, theophylline) can increase it's half-life by blocking the degradation
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Describe desensitization?
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once the Gsa has gone off to do it's thing the beta and theta subunits of G can bind betaARK (BARK)...this phosphorylates BAR...then Barr binds to and blocks the phosphorylated BAR...then, finally, the BAR-Barr complex can be removed from the membrane
-so essentially after the binding epinephrine has had its effect, the receptor is blocked from further interaction with Gs...taken out of circulation, and...eventually returned to the membrane (resensitization) |
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Desensitization broken down into 4 steps?
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1. BARK adds phosphoro group
2. BAR blocks the receptor 3. Receptor moves off membrane into the cell 4. cell can be resensitized |
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cAMP is a what?
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2nd messenger for many regulatory molecules
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Besides cAMP what else is an important 2nd messenger?
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Ca2+
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How is Ca2+ an important 2nd messenger?
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-it's low intracellular conc. means that small changes (as initiated by various ion channels) are relatively large, and easily detected....when the conc. of calcium goes from 0.1 to 1mM it binds to calmodulin (an acidic protein) and changes it's conformation...this then changes the activity of various proteins which it can associate
(so calcium doesn't act directly, it acts on calmodulin which then acts on other molecules) (so calmodulin signals to other proteins that Ca2+ has been released) |