biochem unit 4 Flashcards

Question

What’s in a Membrane: Amphitropic

Answer 1

Tethered to a membrane through a covalent bond to a lipid anchor Anchors are attached by specific enzymesand can later be removed Reversible: sometimes associated,sometimes not

Answer 2

Biological Membranes are selectively permeable Also: semipermeable The lipid bilayer is hydrophobic and is impermeable to most molecules exceptsmall non-polar molecules (like CO2, O2, N2, small steroids) Need membrane proteins for ionic and polar substances Endo/Exocytosis for big things!

Answer 3

Passive (no energy required) vs Active (energy required) Transport Simple (no protein required) vs Facilitated (protein required) Passive Diffusion Primary (uses ATP directly for energy) vs Secondary (uses concentration from primary active transport) Active Transport Uniport (transport 1 molecule) vs Cotransport (transport 2 molecules) Symport (transport 2 molecules in the same direction) vs Antiport Cotransport (transport 2 molecules in the opposite directions) Considerations of movement: Is simple diffusion possible? What is the membrane potential (Vm)? Is there an electrochemical potential?

Answer 4

Simple diffusion involves the movement of each solute byrandom molecular motion from an area of high solute concentrationto an area of low solute concentration Diffusion of small, nonpolar molecules (such as gases O2 and CO2)is proportional to their concentration gradients Does not require a proteinchannel Through the membrane!

Answer 5

Passive transport proteins move uncharged, polar solutes down concentration gradient two types: Transporters Channels Transport proteins decrease the activation barrier (energy) of transport (∆G‡) by binding solute noncovalently Transporters and channels provide a more chemically favorable environment for the diffusion of the solute across the membrane The solute is not guaranteed to cross. Like the transitionstate of enzymatic reactions, it could go either way no energy required

Answer 6

Channels/Ion channels are much faster than transporters, they do not saturate, and do not undergo conformational changes They allow movement (driven by a gradient – millions of ions/second if right) Have one gate Gate opening/closing is regulated by ligands, voltage, mechanical stress Opening/closing is very quick Are somewhat specific for ions MANY DRUGS TARGET ION CHANNELS

Answer 7

Transport proteins decrease the activation barrier (energy) of transport (∆G‡) by binding solute noncovalently (slower than channels!) Transporters have 2 gates Bind specifically (more so than channels) Passive or Active (1°, 2°)Transport Straightforward “steps”: - “Substrate” binds - Transporter changes conformation - Releases substrate on the inside of the cell Kinetics of transport are similar to enzymes!

Answer 8

D-glucose because it has the smallest Kt low Kt: bind well, left of curve high Kt: bind poorly, right of curve

Answer 9

Transport against a concentration gradient Requires input of energy! uniport: transport 1 molecule symport: transport 2 molecules in same direction antiport: transport 2 molecules in opposite directions

Answer 10

In primary active transport, transmembrane ATP-hydrolyzing enzymes provide the energy to drive the transport of ions or molecules In secondary active transport, concentration gradients formed by primary active transport are used to move other substances across the membrane

Answer 11

an antiporter: ATP hydrolysis drives 2K+ in, 3Na+ out these pumps consume ~25% of the energy consumed by humans at rest if it stops working then Na+ builds up in the cell and so water will follow the salt and go inside the cell and cause it to swell

Answer 12

lactose transporter (permease) transports H+ and lactose in the cell proton pump transports H+ out of the cell and at the same time, converts fuel into CO2

Answer 13

1- Na+ K+ ATPase - primary antiporter - move 3 Na+ out and 2 K+ in 2- Na+ glucose symporter (driven by high extracellular [Na+]) - secondary symporter - move 2 Na+ and 1 glucose in 3- glucose uniporter GLUT2 facilitates downhill efflux - move 1 glucose out of cell

Answer 14

simple diffusion protein carrier- no saturable with substrate- no movement relative to concentration gradient- down energy input required?- no channels and pores protein carrier- yes saturable with substrate- no movement relative to concentration gradient- down energy input required?- no transporters and carriers protein carrier- yes saturable with substrate- yes movement relative to concentration gradient- down energy input required?- no primary protein carrier- yes saturable with substrate- yes movement relative to concentration gradient- down energy input required?- yes (direct source) secondary protein carrier- yes saturable with substrate- yes movement relative to concentration gradient- up energy input required?- yes passive transport (no energy required) - simple diffusion - facilitated diffusion - channels and pores - transporters & carrier active transport - active transport - primary - secondary

Answer 15

the concentration of a substrate, in this case glucose, at which the transport protein is at half capacity. A low Kt would mean a high affinity transporter a high Kt means a Low affinity. a lower Kt means it takes less substrate to occupy half the transport space of a protein.

Answer 16

specific sensitive, due to - high affinity - cooperativity - amplification modifiable (desensitization) integration

Answer 17

G-protein coupled receptor - external ligand (L) binding to receptor (R) activates an intracellular GTP-binding protein (G) which regulates an enzyme (Enz- Adenylyl cyclase right?) that generates an intracellular second messenger (cAMP right?)

Answer 18

GPCRs implicated in allergies, depression, blindness, diabetes, Cardiovascular defects more than 1/3 of all drugs on the market today target a GPCR examples of drugs: - blood pressure reducers (beta-blockers such as propranolol) - stomach acid suppressors (ranitidine) - bronchodilators (albuterol) - antidepressants (paroxetine)

Answer 19

propranolol (antagonist) Kd: 0.0046 does! binding site for epinephrine (adrenaline) four types a1, a2, B1, B2 - defined by differences in affinities and response to: agonists: molecules (ligands) similar to the natural ligand, that mimic the ligand's effects antagonists: analogs that bind but have no effect, blocking the effects of agonists - they are inhibitors different types are found in different tissues and have different effects

Answer 20

3 Components of these systems: 1. Plasma Membrane Receptor 2. Guanosine nucleotide-binding protein (G protein) 3. In-membrane effectorenzyme that generates anintracellular 2nd messenger There are 800+ known GPCRs transducing messages such as hormones, growth factors, smells, taste, etc.

Answer 21

GPCRs are 7-TM (transmembrane) (7 amino acid chains, polytopic because it goes through the membrane 7 times, hydrophobic amino acids insde and hydrophlic ones outside) domain α-helical integral membrane proteins Example: - Β-adrenergic receptor Spots for: Ligand-binding Gα interaction sites Gβ interaction sites Regulatory (β-arrestin) interaction sites

Answer 22

Heterotrimeric on the cytosolic side of the membrane stimulatory: Gs (others are inhibitory) initially, G-protein has GDP bound (thus the name) 3 subunits: a (can either be Gi or Gs), B, Y initially, bound to the receptor The G protein is a subunit of Gsa that separates from the B and Y subunits and moves ('slides along') to the effector enzyme (AC). after receptor binds epinephrine, GDP is replaced by GTP GPCR: G protein coupled receptor so it is a receptor on a cell that effects a G prootein to cause an intracellular signal

Answer 23

In our present discussion, we will talk about adenylyl cyclase (AC) Other pathways have other effector enzymes G-proteins can either stimulate (Gs) or inhibit (Gi) AC production of… Cyclic AMP (cAMP)(second messenger) The G protein's a subunit of Gsa separates from the B and Y subunits and moves 'slides along' to adenylyl cyclase (AC) and activates it so that AC catalyzes the synthesis of cAMP 2nd messenger

Answer 24

after activating AC, the GTP bound by Gsa is converted to GDP. Gsa is a GTPase: it can convert GTP to GDP. This inactivates Gsa. Self-inactivation Gsa dissociates from AC, re-associates with its B and Y subunits, and is ready to go again Gs

Answer 25

Gs with GDP bound is turned off; it cannot activate adenylyl cyclase contact of Gs with hormone receptor complex (the complex would have to chnage shape to come in contact with G-protein) causes displacement of bound GDP to GTP Gs with GTP bound dissociates into a and By subunits. Gsa -GTP is turned on; it can activate adenylyl cyclase GTP bound to Gsa is hydrolyzed by the protein's intrinsic GTPase; Gsa thereby turns itself off. The inactive a subunit reassociates with By subunits

Answer 26

Receptor, G-protein, AC

Answer 27

epinephrine binds to its specific receptor allosteric change in hormone-receptor complex causes the GDP bound to Gsa to be replaced by GTP activating Gsa activated Gsa separates from By subunits of G-protein and moves to adenylyl cyclase and activates it. Many Gsa subunits may be activated by one occupying receptor adenylyl cyclase catalyses the formation of cAMP cAMP activates PKA phosphorylation of cellular proteins by PKA causes the cellular response to epinephrine cAMP is degraded, reversing the activation of PKA

Answer 28

cAMP is a common secondary messenger A large number of GPCRs mediate their effects via cAMP (Gs or Gi) allosterically activates cAMP-dependent protein kinase A (PKA)

Answer 29

Kinases are enzymes that catalyze the phosphorylation of hydroxyl groups on Ser, Thr, or Tyr amino acids in target proteins Protein Kinase A (PKA) is a cAMP-dependent protein kinase that targets many proteins in the cell leading to their activation Some targets of PKA lead to glycogen  glucose in the liver (next semester)

Answer 30

AKAPs (PKA anchoring protein) hold together specific ACs, PKAs, and PKA targets so that the cAMP generated by an AC activates (or inactivates) the right PKA and its target enzyme cAMP can mediate multiple signals due to the localization of PKA PKA is localized to particular structures by an anchoring protein different anchors are expressed in different cell types --> determines downstream effect of cAMP amplification: epinephrine cascade This is where the amplification theme comes in. We go from 1 molecule to 100,000

Answer 31

1 molecule epinephrine 1 molecule epinephrine receptor complex (change shape) 10 molecules Gsa (GDP attached to Gsa is replaced by GTP and activates Gsa. Gsa then goes on to activate cAMP) 200 molecules of cyclic AMP (which activates PKA) 100 molecules active PKA 1000 molecules active phosphorylase b kinase 10000 active glycogen phosphorylase a 100000 molecules glucose 1-phosphate This is where the amplification theme comes in. We go from 1 molecule to 100,000

Answer 32

when blood [epi] falls, epi dissociates from the receptor, and G is no longer activated GTPase activator proteins (GAPs) accelerate G protein inactivation cAMP can be hydrolyzed to 5'-AMP (which is not active) by cyclic nucleotide phosphodiesterase - methyl xanthines (caffeine, theophylline [tea]) block the degradation of cAMP, increasing the half-life of cAMP so it is around longer!!!

Answer 33

guanine exchange factor (GEF) - helps exchange GDP for a new GTP GAPs and GEFs - potential drug targets in cancer these are also regulators

Answer 34

Caffeine a methyl xanthine!

Answer 35

enzyme activity is often regulated by phosphorylation (enzyme = kinase) and de-phosphorylation (end = phosphatase) - modified AA = Tyr, Der, Thr examples: PKA, Receptor Tyr kinases phosphorylation may increase or decrease activity

Answer 36

epinephrine B-adrenergic receptor G-protein adenylyl cyclase cAMP PKA

biochem unit 4 Flashcards

(65 cards)