Molecular Bio Exam 2

Signal transduction

when one signal is converted into another signal

reception, transduction, response

what are the 3 general stages of signal transduction

reception

the stage of cell signaling where the ligand binds to the receptor

transduction

the stage of cell signaling where intra cellular signaling occurs moving the signal along

metabolism, cell shape, gene expression

the response stage of cell signaling usually involves altered —, — —, or — —

autocrine, paracrine, contact-dependent, endocrine, neuronal

what are the 5 types of cell communication methods? (APCEN)

autocrine

cell signal that acts on the same cell that produces the signal

paracrine

ligand signal that diffuses locally

contact-dependent

cells that are directly next to each other

endocrine/hormonal

signal travels through the blood stream to find target cells

neuronal

signal called an action potential

variety

an EC signal can lead to a wide — of responses in cells

combinations

cells respond to — of signals and different — can lead to different responses

fast

— signal responses are typically those involved in protein function, muscle contraction, or secretion

slow

— cell signaling usually occurs when there is protein synthesis or cell growth, change in gene expression, or production/degradation of proteins

G-protein

— coupled receptors (GPCRs) are the most common signal receptors in the body

GTP, proteins

GPCRs activate —binding proteins, and initiate cascades by activating or inactivating other —

α, β, γ

G protein subunits

α

the G protien is active when the — subunit has GTP bound

β, γ

activated G-protein causes — and — to dissociate from the molecule

7

A GCPR uses a single polypeptide chain with # transmembrane passes

GDP

the G-proteins will be inactive when the α subunit is bound to —

GDP, inactive, G-protein, GTP, activates, βγ, activate

General cascade of GCPRs: — is bound to the α subunit of a G protein and therefore the protein is —, a GCPR is formed when the — — couples with the transmembrane receptor, a signal molecule interacts with the receptor that then causes a decrease in the α subunit’s affinity for GDP allowing — to bind, this — the G protein and breaks it into the α subunit and the — complex, both parts of the G protein can then — other proteins within the cytosol

hydrolyzing

G-proteins are inactivated by — GTP to GDP, the subunits rejoin

G-protein, βγ, K, depolarize, inactivation, βγ

Activation of Ion Channels in Nerves of Heart: an activated GPCR leads to an activated — —, the subunits break apart and the — subunit interacts with the closed K⁺ channel, by interacting the subunit opens the K⁺ channel, — leaves the cell making it harder to —, α subunit hydrolyzes GTP causing — and the — subunits leave the K⁺ channel allowing it to close

subtypes

there are different — of G proteins

αs, αi

the - and - subtype of G proteins use adenylate cyclase as their second messengers

αq

— is a subtype of G protein that uses phospholipase C as the second messenger

second messengers, cannot

— — are the signals that diffuse through the cell causing the response to the signal, without them the signal — continue

other

some second messengers can pass through the cell membrane to — cells

Adenylyl cyclase

an enzyme that converts ATP into cAMP

cAMP-dependent protein kinase

by converting ATP to cAMP, adenylyl cyclase helps to activate — — — — (PKA) which can change the activity of other proteins/influence gene expression

regulate

cAMP helps to — both fast and slow signal responses

stimulate, inhibit

Gαs proteins — adenylyl cyclase, while Gαi — it

Gαs, activate, into

In the presence of cholera toxins: cholera toxin modifies — protein preventing the α subunit from hydrolyzing GTP, this causes adenylyl cyclase to continuously —, this leads to Cl^- and H₂O flooding — the gut

Gαi, GDP, active

In the presence of pertussis toxin: pertussis toxin modifies — protein, preventing — from leaving the α subunit, this causes adenylyl cyclase to always be — and in the lungs this causes coughing

phospholipase C

subunit Gq of a G protein activates — —

inositol, propagate

phospholipase C cuts — phospholipid (PIP₂) generating IP₃ and DAG both of which — the signal by activating and phosphorylating other proteins

ER

IP₃ causes Ca2 to be released from the — and allows other proteins to be activated

PKA

DAG and Ca2 together activate — which allows for phosphorylation of other proteins

Nitric Oxide, relaxation

endothelial cells produce Ca2+ in response to acetylcholine, Ca2+ causes — — to diffuse into smooth muscle cells adjacent to endothelial causing smooth muscle —, nitroglycerin is a type of NO used to treat Chest pain

transmembrane, activate, differentiation

Enzyme-coupled receptors are — cell-surface receptors that — enzymes, regulate fast and slow responses, and are highly involved in cell growth, proliferation, —, survival

cytoskeleton

enzyme-coupled receptors regulate fast responses that are involved in — changes

gene expression

enzyme-coupled receptors regulate slow responses that are involved in — —

α-helix, dimerize, activation

Receptor Tyrosine Kinases (RTK) are receptors that contain one transmembrane —→ activation occurs when the receptors — to transmit the signal effectively, two intracellular domains of the receptors phosphorylate each other leading to the — of intracellular signaling complexes

tyrosine phosphatases

in order for inactivation of RTKs, — — have to dephosphorylate → allows for dissociation of receptors and ends signal

GTPase, Ras-GEF

RTKs activate Ras (a monomeric —) by activating — which helps activate Ras protein

RTK, phosphorylation, MAP3K, MAP2K, MAPK

the Ras and MAP-Kinase Pathway: Ras protein activated by — and initiates MAP-Kinase — cascade, Ras activates — which uses ATP to phosphorylate — which uses ATP to phosphorylate — which uses ATP to phosphorylate other enzymes that cause changes in protein activity or gene expression

metabolism, apoptosis

the MAP Kinases have many targets that influence cell division, — and —

pathways, signaling, proteins, integration

similarities between GCPRs and RTKs are both involved in many —, both — (prev) and many of these converge on similar —, this leads to an — of signals

LEF1/TCF

— is a family of proteins on Wnt target genes

axin, APC, degradation, GSK3, CK1, degraded, Groucho

Wnt/β-catenin signaling without the Wnt signal: — and — proteins that are structural for holding the — complex together, — and — phosphorylate β-catenin causing it to be ubiquitinated and —, — continues to bind with LEF1/TCF repressing the Wnt target genes

Frizzled, LRP, frizzled, LRP, dishevelled, unphosphorylated, groucho

Wnt/β-catenin signaling with Wnt signal: Wnt binds to — and brings (prev) and LRP together, axin interacts with — and — (a GCPR) receptors bringing everything else in the destruction complex with it, CK1 and GSK3 phosphorylate —, Frizzled recruits scaffold protein — to deactivate LRP and disassemble the degradation complex, — β-catenin accumulates and binds to LEF1/TCF displacing — allowing the transcription of Wnt target genes

smoothened, Ci, PKA, co-repressor

Hedgehog pathway without hedgehog signal: patched blocks — from fusing with the cell membrane, — protein is phosphorylated by —, GSK3, and CK1, and is then ubiqitinized and cleaved, cleaved bits of the Ci protein bind with a — to keep hedgehog target genes off

iHog, patched, Ci, co-activator

Hedgehog pathway with hedgehog signal: the hedgehog signal binds to — and — allowing smoothened to join the cell membrane, Smoothened (a GCPR) is phosphorylated by PKA and CK1 and is activated, smoothened interacts with — and then allows (prev) to be released from its protein complex, Ci interacts with a — to activate the target genes

specialization (differentiation), inhibition, direct, secondary

Notch signaling is primarily done with cell — and lateral —, it is a more — type of signaling as there are almost no — messengers involved unlike other pathways

delta, notch, neighboring, cleaved, notch-responsive

Notch Signal Pathway: the — signal protein on the developing cell binds to the delta receptor (—) on the — cell, the tail of the notch gets — and travels to the nucleus where it activates transcription of — genes

lateral inhibition

— — indicates that a cell is going to differentiate into a particular type of cell and no one around them should do the same, unique to notch signaling

physical, column matrix, bind

column chromatography is used to determine the — interactions of a pathway, a protein X will be attached to a — — and a mixture of proteins will be applied to the column, proteins that — to protein X will stick to the column

physical, antibodies, mixture, centrifugation

immunoprecipitation is used to determine the — interactions of a pathway, it uses — to purify/sort through molecules, a — of molecules are exposed to a specific Ab, the aggregate of the molecules that bind to the Ab are collected via —

function, order, mutating, overactive, upstream

protein mutation is used to determine the — and —of a pathway, this is done by — a protein of interest, prev helps to see what effect/function a protein has or if there is a “natural” mutation in the pathway. To determine the order, a mutated protein will be introduced with an — protein in the pathway and if signaling is restored than the mutated protein is — from the overactive protein

absorption, distribution, metabolism, excretion

what are the 4 main principles of pharmacokinetics (ADME)?

absorption

how will the drug get in?

distribution

movement of a drug from one location with in the body to another

metabolism

the goal of this is to inactivate compounds and make them easier to excrete

excretion

how does the drug leave the body?

inhalation, intravenous, nasal, transdermal, oral, ocular

what are the 6 routes of drug administration?

systemic, active

bioavailability is the proportion of a drug available to — circulation in an — form

first pass, absorption, liver, decreased

ingestible drugs can cause a — — effect, which is where all the — of the drug from the small intestine goes to the — first and by the time it reaches systemic circulation the concentration of the drug has significantly —

1, modification

phase # metabolism is primarily involved in — of the drug by making the compound more water soluble

2, conjugation

phase # metabolism is primarily involved in the — of the drug by adding more functional groups to help with solubility

bioactivation

when a drug is not functional until acted upon by an enzyme

zero order, independent

— — elimination involves a constant amount of a drug being eliminated per unit of time, the rate of drug elimination is — of drug plasma concentration (graph is linear)

first order, proportional

— — elimination involves a constant fraction of drug eliminated per unit time, the rate of drug elimination is — to the drug plasma concentration (graph is exponential)

switch

zero order eliminations will often — to first order after a certain point of decrease

Agonist

drug that provides enhanced cellular activity to a drug, maximizes the effect of the drug

antagonist

drug that blocks cellular the activity that a drug is supposed to cause

partial agonist

drug that enhances but doesn’t maximize the effect of a drug

inverse agonist

drug that binds to the same receptor as the agonist but induces an opposite pharmalogical response

response

EC₅₀ is the concentration where we see 50% of drug — in the body

potency

how much of a drug is needed to produce a response

efficacy

relative ability of a drug to produce a maximal response

lower

a — EC₅₀ is more potent

no-observed-adverse-effect level

NOAEL stands for

lowest-observed-adverse-effect level

LOAEL stands for

window, adverse

the therapeutic — is the range of drug concentration with a therapeutic response without significant — side effects

index

the therapeutic -— compares the amount of drug that causes toxic side effects

lethal dose (at 50%)/ efficiency dose (at 50%)

the TI in animals is calculated by

toxicity dose (at 50%)/ efficiency dose (at 50%)

the TI in humans is calculated

smaller

a — TI indicates that a substance is safer because the toxicity dose is farther from the efficency window

reduced/loss of theraputic effect

drug interaction: when taking two drugs together causes them to cancel each other out/have no effect

adverse/toxic effects

when two drugs interact in a way that causes them to have toxic effects

physical/chemical incompatibility

drug interaction where when the two drugs interact it can cause a number of changes to the drugs, such as precipitation of the drug, pH changes, and effeciency decrease

beneficial/desired

drug interactions that make the drugs more effective

addition

a summation drug interaction is — of the effects of two drugs

more than

a potentiation drug interaction is when the combined effect of the two drugs is — — the sum of their individual effects