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262 Cards in this Set
- Front
- Back
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What percentage of total body weight is water?
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about 50-65% in the protypical person with about 17% body fat
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Total body water acan be divided into:
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ICF (2/3); ECF (1/3) Of the ECF, 3/4 is the interstitial water between cells, and 1/4 is the vascular volume (blood volume after the removal of cells)
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Mean concentrations for sodium and potassium (ECF and ICF)
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ECF: Sodium (136-144), Potassium (3.7-5.2) ICF: Sodium (12) Potassium (150)
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How do you calculate the anion gap?
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(Na+K)-(Cl+bicarb)= ANION GAP
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You chave two compartments, A and B separated by semi-permiable membrane allows water to pass freely across. Membrane does not allow sodium to pass. Add table salt to compartment A. What will happen to the volume of water in compartments A and B?
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Waterwill move from compartment B to compartment A. The force that moves the water is osmotic pressure
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You place an IV in a patient and administer a NaCl solution into a vein. What happens to the volume of the vascular compartment?
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it increases
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How can one decrease the volume of the ECF?
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force the patient to excrete salt using a diuretic. This is how hearth failure is treated
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What are three main routes by which we expend water?
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Insensible or evaporative and not regulated (1. Skin, 2. Respiratory) and 3. Urine
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What is the calorie based total water requirement?
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1cc per calorie
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How do you calculate daily caloric requirement based on weight?
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100 cal/kg for the first 10 kg, 50 cal/kg for the next 10kg, 20 cal/kg thereafter
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Acids and bases basic definition
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acids donate H+ and bases accept H+
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definition of pH
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pH= -log[H+]
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pH in the body
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7.36-7.44 (slightly basic, water is 7)if it falls below 6.8 or rises above 7.8, death occurs
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Henderson Hasselbalch equation
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pH=pKa+log[A/HA]
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the bicarbonate buffer system
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Co2 reacts with water to produce carbonic acid, H2CO3. This reaction can be accelerated by the enzyme carbonic anhydrase. Carbonic acid dissociates into bicarb and is it's own buffer with the excretion of CO2 the blod pH is maintained
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Hypernatremic patient dehydrated because wasn't given water to drink. Water loss in absence of elecrolyte loss
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treatment: administer IV fluids containing extra water
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hyponatremic girl has seizure because serum sodium is low. Was given apple juice for diarrhea. Water without electrlytes.
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treatment: give IV with extra sodium
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diabetic ketoacidocis causes ketoacids to accumulate in the circulation. Patient breathes harder and faster to blow off CO2
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if bicarb decreases but patient's CO2 also decreases, the latter compensates for the former
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carbohydrates
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sugar plus water. Monosaccharides, disacharides, oligosaccharides (3-12), and polysaccharides
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Lipids
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compounds including fats, oils, waxes, sterols, and triglycerides. Insoluble in water and soluble in non-polar solvents
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name the 4 important lipids to know
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Fatty acids, Aglycericerols, sphingolipids, and steroids
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fatty acids
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straight sliphatic chains with a methyl group at one end and a carboxyl group at the other. Saturated, C-C bonds are all singe and unsaturated bonds are double. Trans are unsaturated that are in the trans position
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acylglycerols
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such as triglycerides- glycerol with three fatty acids attached through an ester linkage to a glycerol backbone
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steroids
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includes cholesterol, vitamin D, steroid hormones
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Nitrogen containing compounds
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amino acids, purines, pyrimidines, pyridines, nucleosides, nucleotides
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explain the difference between essential and non essential amino acids
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non essential can be synthesized in the body and essential must be obtained through diet
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list the nine essential amino acids
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isoleucine, leucine, lysine, threonine, tryptophan, methionine, histidine, valine, and phenylalanine….. I Like Light That Tries Making Home Very Pretty
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Define catabolic and anabolic
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catabolic is undernourished and losing weight, anabolic means positive energy balance where intake calories exceed energy consumption
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Total energer expenditure TEE is composed of what?
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Resting energy expenditure (REE, 60%), The Thermic effect of food (10%), and modest physical activity (30%)
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what are FFM and BCM in relation to body composition
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fat free mass, FFM, is composed of extracellular and intracellular water, the bony skeleton, glycogen and skeletal and visceral protein. BCM, body cell mass, is the energy reserves provided by intracellular glycogen, protein, and water
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what is the body composition of the prototypical healthy 70 kg man?
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60% water, 17% protein, 17%fat, 6%carbohydrate and minerals
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energy per gram for glycogen, protein, and fat
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glycogen and protein are 4 cal/gm and fat is 9 cal/gm
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while fasting what are the alternative sources of energy used by the body and how long can a person last?
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alternative energy sources are supplied by ketone bodies from fatty acids (ketogenesis) and by muscle protein (amino acids used for gluconeogenesis). A normal weight person can last ~2 months and obsese people can fast for periods of 12 months or greater
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Why are sick people catabolic?
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the stress of critical illness alters the energy balance. Not the hypometabolism of starvation but rather the hypermetabolism. Skeletal and visceral proteolysis provide amino acids. Promoted by ciculating stress hormones and inflammatory cytokines
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What is the glycemic index?
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The glycemic index is the blood glucose response to a carbohydrate containing food compared to a standard. Influenced by fiber content and particle size. Low does not equate healthy
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LDL and HDL
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Low Density lipoprotein cholesterol (LDL) are mainly cholesterol and called the "bad." High density lipoprotein cholesterol (HDL)has an inverse relationship to heart disease and referred to as "good"
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Kwashiorkor
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Energy sources are adequate but protein intake is low. Swollen abdomen, reddish discoloration of hair and depigmented skin. Abdominal swelling is from ascites (fluid in the abdominal cavity) and enlarged liver due to fatty infiltration
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Marasmus
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inadequate calories in excess of the inadequacy of the protein intake (general starvation)
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excess protein intake
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leads to increased water and salt loss in urine as well as calcium loss. Can lead to osteoporosis
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List five transport mechanisms
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1. Diffusion through the lipid bilayer 2. Diffusion through protein pores 3. carrier-mediated transport 4. active transport (pumps) 5. Endocytosis and exocytosis
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Diffusion
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the passive flow of a substance from a point of high concentration to one of lower concendration merely as a result of random molecular motion. Only useful over short distances: fraction of a milimeter
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Fick's first law
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J=-D(dC/dx), where J is the rate of diffusio (moles/cm3, D is the diffusion coefficient (sm3/sec), Cis the concentration (moles/cm3) and c is the distance in cm ***non charged molecules** can be adapted to flux equation
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Flux
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Flux=-PA(C2-C1) where P is the permeability in cm/sec, A is the membrane area in CM2 and C2 an C1 are the concentrations of the slute on each side of the membrane ***non charged molecules ***
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What types of molecules can and can't diffuse across the bilayer?
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CAN: Hydrophobic molecules (O2, N2, benzene) and small uncharged polar molecules (H2O, urea, CO2, glycerol). CANNOT: large uncharged polar molecules (glucose, sucrose) and charged molecules (ions like H+, Na+, HCO3-, K+, Ca2+, Cl-, Mg2+
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how does acid/base influense dosing?
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acidity will drive a compound to it's protonated form and increase entry (overdose). Opposite will happen if protonated form is charged (under dosed)
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Osmosis
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is the net flux of water across a semi permeable membrane from low solute concentration to high solute concentration. osmolarity of a solution is the # of moles of solute particles per liter of solution (ic). units: per kg of water not liter of solutions
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osmotic pressure
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is the pressure required to prevent the osmotic flow of water. Van't Hoff relation: piis proportional RT(ic). Sigma and theta also used for reflection and imperfect permeability, respectively
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Diffusion via Ion Channels
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ions cross the cell membrane by diffusing through water-filled protein pores called ion channels. Generally referred to as a form of passive transport (no ATP) but know that ATP is consumed in maintaining some ionic gradients
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classes of ion channels
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ligand-gated, voltage-gated, stretch-gated or mechanosensitive, temperature-gated (an also be activated by menthol and capsaicinligands), and light-gated
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selectivity classes of channels
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potassion channels, sodium channels, calcium channels, non-selective cation channels, chloride channels, gap junctions
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selectivity filter
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filters ions for channel. Determinants: size, net charge, electron density, how tightly it holds onto it's associated water molecules
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Carrier-mediated transport
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exhibits specificity, saturation kinetics and competition between transported substrates for binding siteson the carrier protein. relatively slow compared to ion channels (one to few molecules transported at a time
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three classes of carrier mediated transport
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A. facilitated diffusion (speeds down electrochemical gradient) B. Coupled carrier transport (two substrates transported together. symport or antiport.) C. Active transport (fueled by ATP to transport against gradient)
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Diuretic furosemide
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blocks the Na+, K+, Cl- cotransporter so that less water is taken back up in the kidney and more goes out in the urine
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Cardiac glycosides (ouabain, digitalis)
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inhibit the activity of the Na/K pump by binding to the binding site on the extracellular side of the pump. Inhibition of pump causes membrane depolarization, opens voltage gated Ca2+ channels, increased influx of Ca2+ leads to greater contractile force
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Most of the time the cell's membrane potential is ___
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negative
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three things that influence whether or how an ion will flow through a membrane and/or alter a cell's membrane potential:
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1. the ion's concentration gradient across the membrane 2. the existing electrical gradient across the membrane 3. the permeability of the membrane to that particular ion
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Electrochemical gradient
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the combination of concentration gradient and electrical (voltage) gradient =electrochemical gradient
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depolarization
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membrane potential becomes more positive
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hyperpolarization
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membrane potential becomes more negative
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Inward current
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flow of positive charge into a cell; this can result from either the flow of catiens into the cell or the flow of anions out of the cell. on graphs, inward current is plotted downward
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ohm's law
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V=IR I is current and R is resistance
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Nernst equation
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For a membrane permeable to only one iion, the transmembrane voltage gradient, E, is given by the Nernst equation: E=Vi-Vo=-(RT/zF)ln(Ci/Co) OR E=-(61/z)log(Ci/Co)
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Net Driving Force
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Net Driving Force = Vm-Eionthe driving force will attract or repell depending on ion charge and the sign of the NDF
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GHK equation
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takes into account the interactions of multiple ions simplified version at 37C Vm= -61 log[Pna[Na]i+Pk[K]i+Pcl[Cl]o/Pna[Na]o+Pk[K]o+Pcl[Cl]i]
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reversal potential
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is the voltage at which there is no net ionic flux through the open channel. i.e., no net ionic current. Can use GHK when more than one permeability or Nernst if only one permeability
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common mV's to know for reference
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Eca =+120, Ena= +60, Vrev for non selective cation channels is ~0, Ecl and Vrest=-70, Ek=-90
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local or graded potential
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have a local effect because ions leav back out charge fades in time and space
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action potential qualities as opposed to local or graded potentials
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action potentials are propagating, self-regenerating, all-or-none changes in the membrane potential that are typically initiated by local potentials. Travel undiminished across long distances
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The 3 basic phases of an action potential
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1. rapid depolarization 2. falling phase of repolarization back toward the resting potential 3. an undershoot which is more negative than the resting potential and slowly decays back up toward it.
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Ion activity behind the upstroke of an AP
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a local depolarization reaches threshold and cascades the openning of voltage gated sodium channels. Sodium floods in
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Ion activity behind the repolarization of an AP
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The voltage gated sodium channels deactivate and also the potassium channels open and let potassium out (delayed rectifier channels)
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Ion activity behind the undershoot of an AP
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delayed rectifier channels swing the membrane potential toward Ek. As the channels close the membrane returns to the resting potential
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Threshold
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level of depolarization required to open enough Na+ channels to develop an action potential
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Local circuit currents
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positive feedback system for action potential: depolarization of the membrane opens Na+ channels; entering Na+ ions depolarize adjacent membrane, opening more Na+ channels and so forth
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What happens to threshold if many of the Na+ channels are blocked by local anesthetics or neurotoxins?
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threshold will be elevated and action potentials will occur less frquently (ex: Bactine spray)
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How does extracellular Ca2+ interact with normal AP's?
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Ca2+ ions bind to negative charges on the channels and line up along the membrane making the interior of the cell appear to be more negative (hyperpolarized) to the channel receptor and has an inhibitory effect.
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hypocalcemia
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When extracellular calcium falls below normal and Ca2+ leaves the channels and membrane surface relieving channel inhibition and thereby reducing threshold for Na+ channel activation, so that Na+ channels open at less positive voltages
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hypercalcemia
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when extracellular calcium is elevated more sodium channels than normal are inhibited by calcium, raising threshold, thereby depressing excitability of neurons and muscle cells. Weakness, paralysis, coma
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low-calcium tetany
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a condition in which the muscles display an abnormal sustained contraction due to overexcitablity of the motor neurons activating the muscle
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Na channel inactivation
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limits the frequency of repetitive stimulation, since new action potentials cannot occur if all the Na channels are inactivated. Ball and chain mechanism
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absolute refractory period
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period of Na channel inactivation. Prevents the overlap or summing of action potentials
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relative refractory period
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sodium channels are no longer inactivated but the potassium channels are still open, keeping the potential near the Ek. Thus it is harder to elicit an action potential because the membrane potential is farther fromt eh depolarized level (threshold)
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accommodation
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in this state, action potential frequency diminishes, and in extreme cases, spikes cannot be elicited no matter how much depolarizating input occurs.
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hyperkalemia
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elevation of extracellular K+ produces a depolarization that initially increases the "excitability" of nerve and muscle cells. if sustained can lead to accommodation. muscle twitches, seizures, or asphyxiation ->weakness or paralysis from accommodation
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hypokalemia
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decreased extracellular K+ gives hyperpolarization that depresses excitability of nerve and muscle.
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The action potential of many CNS neurons have long lasting ______. What causes these?
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afterhyperpolarizations (AHP's); result from calcium-activated potassium channels after the opening of the delayed rectifier K+ channels. Reduce firing frequency by increasing the relative refractory period.
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Long plateau phase (ventricular)
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occurs in the action potentials of most heart muscles and follows the sodium spike. It results from the Ca2+ channel opennings from depolarization. No undershoot in ventricular AP's
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Sino-atrial pacemaker potential
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characterized by a rhythmic fluctuation in the membrane voltage. Ion channel crucial for the slow positive swing in membrane voltage leading to upstroke is the HCN channel
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HCN channel
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aka the Ih channel, is opened by negative voltages and is regulated by cAMP. HCN stands for hyperpolarization-activated, cyclic nucleotide-regulated channel. HCN is a non selective cation channel
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how pacemaker potential works
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cell starts negative b/c K+ channels open>hyperpolarization triggers HCN open>influx of mainly NA->depolarization->delayed opening of additional K+-sending cell negative again >negativity closes the Ca channers >more hyperpolarization>reactivates HCN
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binding of cAMP to HCN
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causes the channel to open more quickly and at relatively less negative voltages. Positive swing in potential occurs sooner and consequently the upstroke occurs sooner. Higher frequency of AP's
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epinephrine and pacemaking
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epinephrine increases cAMP and thus increases SA node AP's. The epinephrine-induced cAMP also stimulares a kinase that phosphorylates Ca2+ channels, making it easier for them to open
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Bone function
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mechanical (support and protection), synthetic (hematopoiesis), and metabolic (mineral storage, acid-base balance
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bone composition
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primarily composed of calcium and phosphate organized in the form of hydroxyapatite. The other main component of bone is the organic component, which is predominantly collagen
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Membranous bode development happens when and where?
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occurs primarily in fetal and early life in the skull bones and clavicles. It involves development from within a membrane.
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Endochondral ossification occurs where?
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long bones, vertebrae and ribs. Template is a cartilaginous structure which is typically formed at the cartilaginous growth plate.
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describe the structure of bone:
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most (80%) of bone mass is composed of compact bone, which is highly calcified. Cancellous or trabecular bone, which is spongy and less dense makes up most of the rest. Cartilage matrix is present in joints between bones and during developmental stages.
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Bone age
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a concept used to describe the degree of bone maturation. Measure with a hand/wrist xray. Ossification of carpal bones and appearance of the phalangeal epiphyses are evaluated
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Markers of bone metabolism
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minerals (calcium and phosphate), Osteoblast products (serum alkaline phosphatase and osteocalcin), Osteoid break down products (urinay collagen telopeptides and hydroxyproline
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Bone regulating hormones
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Parathyroid Hormone (activates osteoclasts) Estrogen (activates oseoblasts, inhibits osteoclasts) GH/IGF (regulate remodeling, stim growth plate) Vitamin D (calcium absorption, bone remodeling) Calcitonin (reduces serum calcium by inhibiting osteoclasts)
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What to look for on growth charts
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falling outstide the 5th through 95th percentile and/or falling away from the curve shape.
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epiphyseal growth plate
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differentiation chondrocytes (catrilage-producing cells) from a resting state, to proliferating state, to differentiated state. Osteoid is deposited at the end of the growth plate. Eventual senescence of chondrocytes leads to epiphyseal plate closure
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Achondroplasia
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is an autosomal dominant growth disorder from a defect in the FGFR3 (fibroblast Growth Factor Receptor 3) gene. Abnormal growth plates leading to severly shortened bones. They usually have normal sized heads since skull bones develop differently
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Gigantism
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is a disorder that results from excess growth hormone before the growth plates have fused. People can grow to be over 7 feet tall and often die prematurely from CV diseases
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Acromegaly
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is the disorder that results from excess growth hormone after the growth plates have fused. Although these patients may be of normal height (if onset after growth plate fused), joints and facial features become coarse. Hats rings and shoes
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Osteomalacia
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Soft bones due to poor mineralization of newly formed osteoid; most often due to insufficient calcium, phosphate or Vit D. Normally occurs in bones that have fused epiphyseal plates. Pathological fractures
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Rickets
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Osteomalacia of growing bones. Affects the growth plate. Soft bones bend with weight bearing, leading to the characteristic bowing of the legs. Caused in most cases by vitamin D deficiency
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Osteoporosis
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Low BMD (bone mineral density) due to imbalanceof bone formation and resorption. Associated with an increased risk of fractures. Primary type 1 (post men) primary type 2 (after age 75), secondary (any age)
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Risk factors for Osteoporosis
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estrogen deficiency in women, extensive use of glucocorticoids, alcoholism, smoking and sedentary life style
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3 ways to measure bone mass
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Dual energy Xray Absorptiometry (DEXA), Quantitative computed tomograpgy (QCT), Quantitative Ultrasound
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Dual energy X ray Absorptiometry DEXA
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Low radiation exposure, highly reproducible, measures bone density and bone area, no volumetric measurement of bone density
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Quantitative computed tomography (QCT)
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Selective analysis of trabecular bone
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Quantitative Ultrasound
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poor precision, lack of good normative data for measuring bone mass
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Two statistical methods of expressing bone mass
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T-score- SD related to average for young adult at peak bone mass. Z-score- SD related to average for persons of the same age, race and gender
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WHO BMD cutoffs
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Normal T>-1, Osteopenia T(-1 to -2.5), Osteoporosis T<-2.5
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Risk factors for osteoporotic fractures
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family history, weight<127, advanced age, smoking, steroid use>3mo, Early menopause<45y, low calcium diet, low physical activity/weight bearing, alcohol consumption>2drinks/day, low BMD<-2.5
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Osteogenesis Imperfecta
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is a heritable disease of connective tissue (abnormalities in Type 1 collagen)resulting in brittle bones. Recurrent fractures or skeletal abnormalities. Often mistaken for child abuse
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What percentage of the body's calcium and phosphorus are in bone?
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99% of calcium and 85% of phosphorous
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What is intracellular calcium and phosphorus used for?
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Nerve conduction, muscle contraction, energy transfer, cell signaling
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Where is the extracellular Ca++ and P?
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[Ca++] 50% free, 40% bound to protein, 10% complexed with anions; P less tightly regulated, free in serum
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X-linked hypophosphatemic Rickets
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X-linked dominant disorder characterized by extreme hypophosphatemia, renal phosphate wasting, impaired intestinal absorption of Ca and P, and rickets. Defect in PHEX
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Lysinuric Protein Intolerance
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Characterized by osteopenia, big liver, red hair, high ammonia. Due to defect in renal transport of dibasic amino acids (low to absent ornithine, arginine and lysinein blood). leads to low activity of the urea cycle and poor bone formation
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List the three types of muscle:
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skeletal, smooth, cardiac
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structure of skeletal muscle:
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long, thin, parallel cells "fibers." myofibrils bound by sarcolemma. Multinucleated on the periphery. sarcomeres are the functional unit that give striated appearance.
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myofilaments
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actin (thin) and myosin(thick). Interact to produce a contraction
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T-Tubules
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fingerlike invaginations of the sarcolemma into the fiber interior at the Z-lie of the sarcomere
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sarcoplasmic reticulum
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site of release of Ca++ used for contraction. SR is an extensive endoplasmic reticulum network surrounding the myofilaments
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describe the relation ship between calcium, troponin, and tropomyosin
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intracellular calcium is binds to troponin, which unfurls the tropomyosin and exposes the myosin binding site on the actin
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Describe the role of ATP in muscle contraction
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1. binding to myosin heads allows for release 2. hydrolysis is required for re-cocking the myosin head 3. powers uptake Ca pumps in the SR and in the plasma membrane (esp. important in smootha nd cardiac b/c Ca comes from outside)
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phosphocreatine
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can be used with ADP to produce ATP. Large stores of it in muscles cells for energy use.
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Isometric contraction
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is generation of tension with no change in the muscle length
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Isotonic contraction
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is a shortening of muscle with a constant load
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Series elastic component (SEC)
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component in the muscle including tendons, ligaments, z-line material, crossbridge. The sarcomere shortening must first take up lack in this SEC and stretch it before any external tension can be generated. Promotes smooth, graded movements
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Temporal and spatial summation in skeletal muscle
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summation of AP's from intracellular calcium accumulation leads to broad and sustained AP's. tetanus
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two types of sensory receptors give feedback to control skeletal muscle contraction
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muscle spindles and golgi tendon organs
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Muscle spindles
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specialized "intrafusal" muscle fibers arranged in parallel with notmal "extrafusal"muscle fibers that generate forge. Spindles report muscle length and rate of muscle stretch
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Golgi tendon organs
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bare nerve endings that are intertwined among collagen matrix of the tendon near where it connects to the muscle. Receptors report the force generated by the muscle. When the muscles contract, or are passively stretched, golgi fires feedback to brain
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6 ways smooth muscle is different from skeletal
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1. no T-tubules or sarcomeres>not striated 2. diff actin and myosin 3. lack troponin: calmodulin>myosin light chain kinase>phosphorylate myosin>actin bind 4. Ca most from outside 5. slower contract 6. gap juncts, pacemaker activity, respond to stretch
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Ways cardiac is like smooth muscle
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gap junctions, pacemaker activity, extracellular Ca used
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Ways cardiac is like skeletal
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striated, have sarcomeres, have t-tubules, tropomyosin and troponin
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DNA basic characteristics
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unit of inheritance, long polymer of nucleotides, 4.6 billion years old, linear in complex eukaryotes, circular in prokaryotes, mitochondria, and chloroplast
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Nitrogenous bases in DNA and RNA are
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Adenine, Guanine, Cytosine, Thymine, Uracil
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Purines
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Adenine and Guanine
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Pyrimidines
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Cytosine, Thymine, Uracil
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What is the difference between nucleosides and nucleotides?
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Nucleosides are nitrogenous bases attached to a ribose or deoxyribose sugar. Nucleotides also have at least one phosphate group attached as well
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Phosphodiester bonds
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nucleotides can be adjoined together by a phosphodiester bond. The bond attaches the 3' carbon of one ribose or deoxyribose to the 5' of the next
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5' and 3'
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DNA is synthesized and read 5' to 3' the 5' end has a free phosphate group and the 3' has a free hydroxyl
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Nucleoside analogs
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if a nucleoside lacks the 3' hydroxyl group, then a phosphodiester bonds cannot be added. Nucleoside analogs are used to restrict replication of cancer and viruses
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Hydrogen bonds bind which nucleotides together? How many bonds?
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C-G with 3 hydrogen bonds, A-T with 2 hydrogen bonds
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Chargaff's rule
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A=T, C=G, so A+G=C+T
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Two complimentary strands of DNS line-up ____
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anti-parallel
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major and minor grooves
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provide the loading dock for DNA binding regulatory bindng proteins and drugs
|
|
|
what stabilizes the structure of the double helix?
|
hydrogen bonds, hydrophobic nature of nucleotides, base stacking, negative charge of phosphates stabilize the structure
|
|
|
3 different structural forms of DNA
|
B form (chromosomal, 10, right) A form (high salt, 11, right, Z form (rare but native, 12, left)
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Histones
|
H2A, H2B, H3 and H4 form octamers called nucleosome, DNA wraps twice around these, then once around the linker histone (H1), collection called the nuclear scaffold
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|
The region of DNA near the end of the chromosome is called the ____ and the region at the center is called the _____
|
telomere, centromere
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Replication Step 1: DnaA protein
|
Binds to AT rich nucleotide sequences and separates the complimentary DNA strands.
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Replication Step 1: Single-stranded DNA-binding (SSB) proteins
|
-help prevent the single stranded DNA from re-forming double stranded DNA, protect against ssDNA cleavage
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Replication Step 1: DNA Helicase
|
After the DnaA protein separates the DNA strands, DNA helicase unzips the double stranded DNA
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Tpopisomerases
|
remove supercoils from DNA helices in replication. Type 1 cuts 1 strand, type 2 cuts 2 to uncoil. Target of quinolone antibiotics like ciprofloxicin
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Replication step 2: replication fork
|
leading strand, lagging strand with okazaki fragments, DNA polymerase adds nucleotides, DNA ligase joins strands
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Primase
|
primase synthesizes the RNA primer ~10 nucleotides long for DNA polymerase to begin with
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Primosome
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Protein complex including primase that displaces any proteins that have bound to the unwound single stranded template (such as SSB)
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DNA polymerase III
|
Adds nucleotides along the single stranded template
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Telomerase
|
a reverse transcriptase that is composed of protein and an RNA template. DNA polymerase can the complete the other strand, longer strand loops back onitself to protect telomere from nucleases (TRF1 and TRF2)
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where are telomere length maintained by telomerase?
|
in germ cells and in transformed (cancerous cells). In somatic cells, telomeres are just gradually shortened with every division
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Eukaryotic DNA polymerases
|
DNA Pol I (beta, repair) DNA pol III (alpha, primase and DNA synthesis)
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Three types of DNA repair mechanisms
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DNA mismath repair- exonuclease activity proofreads new DNA, UV endonuclease- repairs damage caused by UV light, Base excision repair- repairs mismatches
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causes of DNA damage
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chemical, radiation, faulty proofreading, free radicals
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Mismatch repair
|
Mut, a repair system: newly synthesized (unmethylated) strand is cleaved; mismatch is removed by an exonucleaseand replaced, ligated. Ex: non-polyposis colorectac cancer
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Nucleotide Exicsion Repair
|
UV lightdimerizes adjacent pyrimidines, UV specific endonuclease recognizes and nicks the phosphodiester backbone, nucleotides removed, DNA polymerase fills the gap, ligase reseals. Ex: xeroderma pigmentosum
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Base excision repair
|
cytosine can be deaminated into uracil, recognized by glycosylases that remove the uracil from the phosphodiester backbone, apyrimidinic-endonuclease removes the phosphate backbone at the AP site, DNA polymerase adds nucleotides, ligase seals
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Polymerase Chain Reaction (PCR
|
a method to amplify a selected sequence of DNA in the test tube
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Steps for PCR
|
1. heat 2. cool and add primers for flanking region 3. add nucleotides and special heat stable DNA polymerase 4. Heat up to denature DNA again and repeat
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What are the structural differences between RNA and DNA?
|
RNA is single stranded not double stranded, RNA has Uracil instead of Thymine, RNA is ribose and DNA is deoxyribse
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The ____ strand replicates with Okazaki fragments
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lagging
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DnaA protein separates the DNA strands at _ _ rich sequences?
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A T
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After separating the DNA, how is the newly exposed single strand of DNA spared from nucleases?
|
single stranded binding proteins
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What unzips the two strans of DNA during DNA synthesis?
|
helicase
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What is the function of topoisomerase?
|
to prevent supercoiling of the template strands during DNA replications
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Once added to a DNA strand, nucleoside analogs inhibit further elongation because they lack ______
|
3' OH groups
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In prokaryotes, ______ contains both a polymerase and an 3'-> 5' exonuclease function
|
DNA polymerase III
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What type of repair removes a nitrogenous base with glycosylase without initially nicking the phosphodiester backbone?
|
Base excision repair
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During the process of mismatch repair, DNA polymerase I can distinguish between the parent and the newly synthesized strands because the ______ strand is methylated
|
parental
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Proteins
|
linear polymers of amino acids, most abundant and functionally diverse class of molecules in living organisms
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functions of proteins
|
catalysis, transport, mechanical support, motion, recognition, senstation, regulation of gene activity, osmotic force
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regulatory mechanisms for proteins
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rate of transcription, RNA splicing, RNA degradation, rate of translation, rate of protein degredation, transport of the protein to final location, post-translational modification of the protein
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|
There are ___ amino acids, and in the body they exist in the _ isoform except for _____
|
20, L, Glycine
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What are the 4 categories of amino acids?
|
non-polar, uncharged polar, acidic, basic
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non polar Amino acids
|
Alanine, Glycine, Isoleucine, Leucine, Methionine, Phenylalanine, Proline, Tryptophan, Valine
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uncharged polar
|
Asparagine, Cysteine, Glutamine, Serine, Threonine, Tyrosine
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Acidic
|
Aspartic Acid, Glutamic Acid
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Basic
|
Histidine, Arginine, Lysine (His Arduous Lie, or BLAH)
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|
which amino acid interrupts alpha helices and contributes to the structure of fibrous proteins like collagen?
|
Proline (ring structure)
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|
Which amino acid contains a sulfhydryl group that can form a disulfide bond?
|
cystine (ex: INSULIN)
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|
What are the only three amino acids that can be phosphorylated?
|
Serine, Threonine, and Tyrosine
|
|
|
protein ____ phosphorylate proteins and protein _____ dephosphorylate proteins
|
kinases, phosphatases
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|
|
Which amino acids can serve as the site of attachment for oligosaccharides?
|
serine, threonine, asparagine
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|
|
other than phosphorylation and glycosylation, what other post translational modifications happen to proteins?
|
addition of saturated fatty acid, addition of a cofactor, addition of smal moeieties (acetylation, methylation, iondination), modification of amino acid side chains (deamidation)
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|
|
primary structure of proteins
|
amino acid sequence. Written with amino terminus at left and carboxy termins at right
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secondary structure of proteins
|
hydrogen bonding between nearby amino acids result in helices and sheets
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tertiary structure of proteins
|
interactions between non-adjacent amino acids resulting in the folding of domains and arrangements of domains
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|
|
quaternary structure of proteins
|
interactions between polypeptides
|
|
|
Protein denaturation
|
unfolding of a protein. caused by heat, organic solvents, strong acids or bases, detergents, or heavy metals. Can be reversible but often it is not
|
|
|
Chaperones
|
aka heat shock proteins that promote proper folding in other proteins
|
|
|
examples of protein misfolding
|
amyloidoses like in alzheimer's disease. Prion disease or Creutzfeldt-Jacob disease is when a misfolded version of prion protein has the same primary stucture but diff secondary---beta instead of alpha causes accumuation of abnormal protein
|
|
|
how many cell types in the human body?
|
at least 4,000 (much more than the 230 previously thought)
|
|
|
Elhers-Danlos syndrome
|
collagen mutatation
|
|
|
RNA structure
|
unbranched polymeric molecule, monomucleotides joined by phosphodiester bonds, ribose sugar, signle stranded, uracil instead of thmidine, capable of folding into complex structures
|
|
|
Five Types of RNA
|
Ribosomal RNA (rRNA), Messenger RNA (mRNA), Transfer RNA (tRNA), Small Nuclear RNA (snRNA), RNAi
|
|
|
Ribosomal RNA
|
Components of ribosomes, found in complex with proteins, sites for protein synthesis.
|
|
|
Transfer RNA
|
smallest stable RNA, 74-95 nucleotides long, at least one tRNA for each 20 amino acids, adaptor molecules to transport a specific AA to the site of protein synth, 15% of all cellular RNA
|
|
|
Messenger RNA
|
500 to 6000 nucleotides, contains genetic info for synthesis of specific polypeptides
|
|
|
Prokaryote RNA synthesis: initiation
|
RNA polymerase binds to the Promoter region, Holoenzyme (core enzyme +sigma factor) recognizes and binds to thhe promoter region
|
|
|
promoter region
|
highly conserved sequences like the Pribnow box -10 and 035 nucleotides from the coding region
|
|
|
Prokaryote RNA synthesis: Elongation
|
RNA polymerase begins synthesizing RNA transcript, sigma factor dissociates, core enzymes unwind DNA, no proofreading
|
|
|
Prokaryotic RNA synthesis: Termination
|
Rho dependent and Rho independent
|
|
|
Rho dependent termination
|
termination signal is recognized with a protein called rho factor, Rho factor moves along mRNA (using ATP) behindthe RNA polymerase, binds to c-rich region and displaces the DNA strand
|
|
|
Rho independent termination
|
newly synthesized RNA molecule has sequence that allows for creation of a hairpin structure, RNA sequence at 3' end is rich in U's which bind to the A's on the template strand, newly synthesized RNA separates from the DNA template, hairpin loop formed
|
|
|
Differences between eukaryotics and prokaryotic transcription
|
eukaryotes have 3 types of RNA polymerases; in addition to promoter region (also in prokaryotes), Eukaryotic expression is also regulated by chromatic structure, enhancers, and inhibitors; Eukaryotic RNA is modified after transcription
|
|
|
Three types of Eukaryotic RNA polymerases
|
I synthesizes precursor of large rRNA, II synthesizes precurors of mRNA and some snRNA, III synthesizes small RNA (tRNA, 5S rRNA, some snRNA)
|
|
|
Eukaryotic transcription initiation promoter regions
|
two promoter regions: TATA (Hogness) and CAAT box, cisacting
|
|
|
Enhancer
|
a region of eukaryotic DNA up or downstream of the promoter region. Transcription factors bind to the region and bend the DNA around to stabilize the initiation complex, enhancer is cis-acting and the binding transcription factors are trans acting
|
|
|
Alpha-amanitin
|
found in some poisonous mushrooms and inhibits RNA polymeraase (deadly toxin)
|
|
|
How does chromatin structure regulate gene expression?
|
Tightly wound chromatin (heterochromatin) cannot be transcribed, loosely wound (euchromatin) can be transcribed, methylated DNA is generally not transcribed, acetylation of histones relaxes chromatin structure
|
|
|
Post transcriptional modifications of Eukaryotic mRNA
|
5' capping, poly A tail, removal of introns, RNA editing, Enzymatic degradation
|
|
|
5' cap
|
7 methyl-guanosine linked by 5'-5' triphosphate link, permits initiation of translation, increases stability
|
|
|
Poly A tail
|
100-200 AMP residues added to 3' promotes stability and facilitates export from nucleus
|
|
|
Removal of introns
|
only in aurkaryotes, Spliceosome removes introns and joins exons together. remember snRNP's
|
|
|
Alternatice splicing
|
a precursor mRNA can be spliced in multiple combinations allowing diversity of protein coding capacity. Ex: different troponins in skeletal and cardiac muscle
|
|
|
RNA editing
|
insertion or deletion of nucleotides in a transcript. Ex: apolipoprotein B100 and B48 found in the liver and small intestine respectively. Deamination of a cytosine to uracil resulst in a stop codon, truncation and the intestinal version
|
|
|
enzymatic degredation as regulation
|
degredation depends on the length of the poly A tail.
|
|
|
What is the majority of cellular RNA?
|
mRNA
|
|
|
What are the two types of synapses
|
Chemical and electrical
|
|
|
Electrical synapses
|
generally used to produce synchronous responses among similar cells. Consist of direct intercellular electrical connections through the ion channels in gap junctions
|
|
|
Chemical synapses
|
used when there is a requirement for amplification or multiple discrete inputs and outputs. Involve release of chemical neurotransmitters which either open post synaptic channels or activate G- Proteins to generate second messengers to open channels
|
|
|
Desensitization
|
process by which some ligand gated ions channels including acetylcholine receptor channel, become less responsive to the ligand with continued exposure
|
|
|
How does acetlycholine work?
|
Ach released into neuromuscular junction, open nonselective cation channels, currents depolarize cell, endplate potential EPP- local potential- pushes above threshold, AP. Leftover Ach either diffuses out of cleft or is broken down by acetylcholinesterase
|
|
|
Myasthenia gravis
|
EPP is subthreshold b/c Ach receptor channels are destroyed > muscle weakness. Treat with acetylcholinesterase inhibitors
|
|
|
alpha-bungarotoxin and curare
|
a snake toxin and a plant toxin from poinson dartsboth block Ach receptor channels
|
|
|
botox and calcium channel blockers
|
both are presynaptic disruptors. Former breaks down snares so no neurotransmitter is released, latter reduces fusion of vesicles by blocking calcium entry
|
|
|
nerve-nerve synapses
|
1. typically subthreshold and very small 2. have inhibtory and excitatory postsynaptic potentials (EPSP's and IPSP's)3. unlike muscle, postsynaptic cells must integrate numerous inputs from various sources to decide whether to fire and AP
|
|
|
Nerve EPSPs
|
depolarizations that drive postsynaptic membrane toward threshold usually due to openning of non selective cation channels. Glutamate and aspartate frequently used
|
|
|
Nerve IPSP's
|
keep membrane below threshold by opennign either K+ or Cl- selective ion channels. GABA is a common inhibitr.
|
|
|
Inhibitory Interneurons
|
often used to convert or expand an excitatory pathway into an inhibitory one
|
|
|
the 9 essential amino acids
|
Valine, Phenylalanine, Methionine, Arginine, Tryptophan, Threonine, Histidine, Isoleucine, Lysine, Leucine (Any Help in Learning These Little Molecules Proves Truly Valuable
|
|
|
Stop codons
|
UAA, UGA, UAG
|
|
|
Types of mutations in genetic code
|
Silent (same amino acid), Missense (Different amino acid), Nonsense (results in a stop), Tandem repeats, Frame shift, Splice site mutations
|
|
|
tRNA
|
Have an anticodon (read codon), and AA attachment site (3' end to carboxyl end), and aminacyl tRNA synthetase (attach AA with ATP for energy- the real translators).
|
|
|
Wobble hypothesis
|
mechanism by which tRNAs can recgnize more than one codon. First base of anticodon in tRNA can engage engage in non traditional base pairing with third base in codon
|
|
|
Ribosome binding sites
|
A- site for incoming tRNA, P site for growing peptide, Esite for tRNA before it exits
|
|
|
initiation of translation
|
components assemble, GTP used for energy, Met tRNA enterPsite first, fully functional ribsosome assembles.
|
|
|
Tetracyclines
|
interacti with small ribosomal subunits blocking access of aminoacyl-tRNA to the mRNA ribosome complex
|
|
|
Puromycin
|
Bears a structural resemblance to aminacyl tRNA and ecomes incorporated into the growing peptide change causing inhibition of further elongation
|
|
|
Chloramphenicol
|
inhibits prokaryotic transferase, inhibits mitochondrial protein synthesis
|
|
|
Clindamycin and erythromycin
|
binds irreversibly to a site on the large subunit of bacterial ribosome h=inhibiting tanslocation
|
|
|
Diphtheria toxin
|
inactivates eukaryotic elongation factor preventing translocation
|
|
|
MicroRNAs
|
block the initiation of protein synthesis. RNA interference
|
|
|
Si RNA
|
lead to cleavage of mRNA and break them down. RNA interference
|
|
|
Ribosomes on the RER synthesize what proteins?
|
Ones to be exported, becomes part of the plasma membrane, lysosomal enzymes, translocated proteins from cytosol
|
|
|
post translational modifications
|
Phosphorylation, glycosylation, hydroxylation, ubiquination (signals for breakdown)
|
