Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Biochemistry I > Midterm 3 > Flashcards

Midterm 3 Flashcards

1
Q

What is the cell signaling pathway

A

linked set of biochemical reactions that are initiated by ligand-induced activation of a receptor protein and terminated by a measurable cellular response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Components of signaling pathways

A

●First messengers: extracellular ligands that bind to receptor proteins
●Second messengers: intracellular signaling proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is signal transduction?

A

●biochemical mechanism responsible for transmitting extracellular signals across plasma membrane and throughout the cell
●also involves second messengers and a variety of intracellular signaling proteins
●function together to transmit, amplify, and terminate signal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what do first messengers do?

A

●binds to receptor proteins, causing conformational change in receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Consequences of signal transduction

A

●changes information into chemical signal
●often ends with covalent or noncovalent modification of intracellular target proteins (phosphorylation and dephosphorylation)
●altered rate of protein expression (at transcriptional or translational level)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

First messenger examples

A

●Insulin: first 1st messenger protein to be discovered, discovered as treatment for diabetes
●Hormones: biologically active compounds that are released into circulatory system and come into contact with hormone receptors in target cells (generally hydrophobic and nonpolar)
●Other soluble gases (NO: generate in cells via oxidative deamination of arginine, causes vasodilation and increased blood flow)
●Neurotransmitters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How do hormones travel?

A

●Endocrine hormones: produced by secretory glands and are exported into the circulatory system. long distance
●Autocrine and Paracrine hormones: small peptides that function over short distances to activate receptors on nearby cells (paracrine hormones) or on same cell (autocrine hormones)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Endocrine Hormones

A

insulin, estrogen, testosterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Paracrine Hormones

A

serotonin, histamine, growth factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Autocrine Hormones

A

interleukins and growth factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are secondary messengers?

A

small, nonprotein intracellular molecules that amplify receptor-generated signal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Secondary Messengers examples

A

Cyclic GMP (cGMP), cAMP, Diacylglycerol (DAG), Inositol-1,4,5-triphosphate (IP3), Ca2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Signal Amplification

A

process by which a signal that is initiated at the cell surface leads to multiple downstream events through the action of enzyme-mediated catalyzed reactions like phosphorylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the receptor protein classes?

A

GPCRs, KLRs, tumor necrosis factor receptors, and nuclear receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

GPCR

A

●G protein-coupled receptors
●involved in sensory perception (vision, taste, smell)
●7 transmembrane alpha helices
●Many are glycoproteins (help with cell recognition) that contain carbohydrate functional groups directly attached to the extracellular domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

GPCR signal transduction

A

●transmit extracellular signals to cytoplasm through direct interaction with membrane-bound protein complex called heterotrimeric G protein (has a G α , G β, and G γ subunit)
●Gα is a GTPase (active when GTP bound, inactive when GDP bound)
●When the trimeric G protein binds to activated GPCR, GDP -> GTP, activating the Gα subunit. Causes dissociation of alpha subunit
●Dissociation of heterotrimeric G protein complex is common to all GPCRs
●lipid membrane anchors (can move but stay on membrane)
●Several different α, β, and γ subunits- causes unique effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Different G alpha subunit examples

A

●αt, αs, αq

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Gαt subunit effects

A

αt activated by GTP -> cGMP phosphodiesterase (break down phosphodiester bonds) -> GMP
●regulates synaptic transmission in light-stimulated vision (just one example)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Gαs subunit effects

A

αs activated by GTP -> ATP turned into cAMP by Adenylate cyclase -> cAMP triggers PKA (phosphokinase A) -> activates numerous target proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Gαq subunit effects

A

αq activated by GTP -> PIP2 converted to DAG and IP3 by phospholipase C (cleave phospholipids in membrane) -> (IP3 -> Ca2+) and (DAG -> PKC) -> regulates many processes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Cyclosporine explained

A

●immunosuppressant
●calcineurin inhibitor
●calcineurin forms phosphatase complex consisting of catalytic subunit that binds to calmodulin and a regulatory subunit that binds to calcium
●inhibition of calcineurin disrupts the transcription of IL-2 and other cytokines within T lymphocytes, so it interferes with T-cell activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

GPCR Signaling in Metabolism

A

●multiple diff stimuli work together to accomplish common goal
● glucagon is peptide hormone released by pancreas in response to low blood glucose levels
●glycogen is the way we store glucose until we need it
●epinephrine= adrenaline, many physiological effects, eg increase heartrate
●Shared pathways: same pathway
●Parallel pathways: same end result, same upstream portion (first messengers)
●makes sense because they (glucagon and epinephrine) signal for same phenotypic response (increase blood glucose levels)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

PKA’s role in Epinephrine (β2 Bound) and Glucagon

A

●Gsα activation of adenylate cyclase, produce cAMP that will activate Protein Kinase A, ***Turns off glycogen synthesis, turn on glycogen degradation and glucose synthesis -> net glucose export

24
Q

PKA role in Epinephrine (α1 Bound)

A

●Gqα activation of PLC -> PIP2-> DAG and IP3 -> (DAG activation of PKC -> turn off glycogen synthesis) OR (IP3 mediated calcium release from ER -> turn on glycogen degradation) -> Net glucose export

25
Q

Catecholamines

A

●1st messengers, include epinephrine
●derived from Tyr
●target α and β adrenergic receptors. Tissue distribution and physiological responses governed by these two receptors are diverse, controlling from metabolism in liver, skeletal muscle, and adipose cells, to relaxation and contraction of smooth muscles

26
Q

Receptor Agonists

A

●Activate receptor signaling by mimicking the natural ligand
●some endogenous agonists: dopamine and norepinephrine
●

27
Q

Catecholamines in detail

A

●β-2 receptors mostly in airway smooth muscles, epinephrine binding to β-2 receptors causes changes in Gαs subunit
●GDP bound state: Gαs interacts with Gβy through switch II helix region
●GTP binding to Gαs induces conformational change in switch II helix region so it’s positioned to bind with adenylate cyclase (perfect binding site for adenylate cyclase)
●adenylate cyclase becomes active upon binding to Gαs
●Elevated cAMP levels activate PKA
●cAMP binds to regulatory subunit of inactive PKA to create active PKA monomers
●PKA free to phosphorylate other proteins (in response to β-2 activation, PKA phosphorylates MLCK- enzyme crucial for smooth muscle contraction-, as it phosphorylates myosin light chains (MLC), enabling interaction with actin for contraction)
●PKA phosphorylating MLCK reduces its activity -> decreases MLC phosphorylation -> inhibiting smooth muscle contraction and promoting relaxation

28
Q

Epinephrine stimulation of β-2 consequences

A

●cause dissociation of Gαs-> produce cAMP
●cAMP will activate PKA (functions to phosphorylate various enzymes contributing to relaxation of airway smooth muscles)
●cAMP reduces Ca2+ by inhibiting outflow (preventing muscle contraction)

29
Q

Receptor agonist and antagonist

A

●Agonist: activate receptor signaling by mimicking natural ligand
●Antagonist: bind to receptor with high affinity and block binding of physiological agonists without promoting structural changes needed for signal transduction

30
Q

Termination of GPCR Signal

A

●G-protein’s activity controlled by 2 proteins:
●Guanine nucleotide exchange factor (GEF): activate signaling, promote GDP-GTP exchange
●GTPase activating proteins (GAP): inhibit signal transduction, stimulate intrinsic GTP hydrolysis activity (inactivate GTP)
●desensitization of receptor after Gαβγ dissociation
●regulatory proteins called G protein-coupled receptor kinases (GRK) phosphorylate GPCR cytoplasmic domain on Ser and Thr residues
●phosphorylation by GRK provides docking site on GPCR for 2nd protein (β-arrestin), a protein that binds to receptor and prevents reassociating with Gαβγ complex
●β-arrestin binding “flags” the GPCR for endocytic translocation to cytoplasm where GPCR is dephosphorylated (not reversible until dephosphorylated)
●After GPCR dephosphorylation in endocytic vesicles, receptor is either degraded or returned to plasma membrane for another round of signaling

31
Q

Receptor Tyrosine Kinase Signaling

A

●RTKs (subclass of KRT) transmit extracellular signals by ligand activation of intrinsic tyrosine kinase function found in cytoplasmic tail of receptor
●activated RTKs are dimers
●activated RTKs phosphorylate downstream signaling proteins that bind to RTK phosphotyrosines (include adaptor proteins- acts as molecular bridges to bring together other proteins- and other kinases
●ex: Epidermal growth factor receptors (EGFR), insulin receptor (defect= type 2 diabetes)

32
Q

Growth Factors Binding to RTKs

A

●ligand binding -> receptor dimerization and kinase activation
●phosphorylation of RTK cytoplasmic tails -> protein binding to RTK phosphotyrosines and phosphorylation of target proteins
●activation of downstream signaling pathways
●defects in EGFR can result in cancer (cell division= too much growth)

33
Q

EGFR signaling

A

●epidermal growth factor is serum growth factor that binds to EGFR and stimulates receptor dimerization on cell surface-> phosphotyrosine (pY) residues in RTK form binding sites for intracellular adaptor proteins containing Src kinase homology-2 (SH2) domain (necessary for phospho residue to bind) -> GRB2 binds to pY residues in EGFR and recruits GEF signaling (helps swap GDP to GTP) called son of sevenless (SOS), which binds and activates G protein called Ras -> phosphorylation causes cascade mediated by trio of related kinases (called mitogen-activated protein kinase (MAP kinase) pathway)
●SH2 examples: phosphoinositide 3 kinase

34
Q

Ras mutation

A

●dephosphorylator not active -> MEK stays active (cell proliferation)

35
Q

What are enzymes?

A

proteins

36
Q

Lock and key mechanism

A

●substrate binds perfectly to enzyme
●can’t explain enzyme regulation or how substrates were binding to sites deep within interior of protein

37
Q

NO as first messenger

A

●NO to guanylate cyclase
●GTP to cGMP and PP
●cGMP to protein kinase G and causes vasodilation
●cGMP phosphodiesterase breaks down cGMP to GMP

38
Q

Induced fit mechanism

A

●substrate binding to active site induces change in enzyme
●enzyme is flexible to accommodate ill-fitting substrate
●primary conformation is “trapped” by ligand binding -> induced fit to optimize interaction
●allows for larger amount of weak interactions between substrate and enzyme
●conformational changes can be minimal (lock and key mechanism) or drastic (fly trap ex)

39
Q

induced fit mechanism example

A

hexokinase, a metabolic enzyme

40
Q

enzyme structure and function

A

●enzyme bind to substrate with high affinity and specificity
●active sites in enzyme bind substrates and promote catalytic reactions (chemical environment for rxns)
●enzyme activity is highly regulated (dont waste energy)

41
Q

Modes of enzyme regulation

A

●bioavailability: amount of nutrient or enzyme present in cell that is capable of participating in biochemical process
●catalytic efficiency: maintained by binding of regulatory molecules or covalent modifications (some molecules binding can increase efficiency)

42
Q

Enzymes as chemical catalysts

A

●alter rate of rxn without changing ratio of substrates and products at equilibrium
●decrease activation energy to speed up rxn
●DOES NOT CHANGE DELTA G

43
Q

Activation energy definitions

A

●energy barrier that must be overcome for reactants to transform into products
●some reactions can be energetically favored, but still must get energy to reach the products
●transition state: high-energy state molecules must go through to get from reactant to product (only there for picoseconds, can’t be isolated)
●activation energy: energy required to reach transition state
●higher activation energy= slower rate of rxn

44
Q

Activation energy collisions

A

●rxn between molecules are result of collisions
●Activation energy: minimum energy needed for collisions to lead to a rxn
●Collisions need enough energy and proper orientation to overcome activation energy

45
Q

How do enzymes increase rate of rxn (how is activation energy lowered)?

A

●stabilize transition state lowers activation energy
●provide alternate path for product formation, could involve formation of stable rxn intermediates that are covalently attached to enzyme (can be multiple steps)
●reduce entropy by orienting substrates appropriately for rxn to occur
●ALL FACILITATED BY ENVIRONMENT OF ACTIVE SITE

46
Q

Active site contributes to catalysis

A

●enzyme active site contains binding sites to select substrates and align reactive groups correctly
●substrates have relatively high binding affinity for enzyme active site (NOT TOO STRONG THO BECAUSE IT MUST BE RELEASED AFTERWARDS)

47
Q

Chemical/Physical properties of active site that contribute to catalytic properties

A

●sequestered microenvironment: provides optimal orientation of substrate relative to reactive group, excludes excess solvent that could interfere with the rxn (ex: aldolase)
●binding interactions between substrate and enzyme to help create a transition state (or stabilize transition state)
●presence of catalytic functional groups: three most common catalytic rxn mechanism in enzyme site (acid-base, covalent, and metal-ion catalyst), cofactors and coenzymes are helper molecules that provide additional chemical groups to supplement protein when amino acids are insufficient to mediate a particular catalytic mechanism

48
Q

Aldolase example

A

●aldolase rxn in gluconeogenic pathway converts two phosphorylated three-carbon compounds into one bisphosphorylated six-carbon compound
●change causes more touch -> more interactions

49
Q

schiff base

A

●know mechanism
●primary amide to aldehyde or ketone (condensation rxn)
●more favorable way to form c-c
●electron sink: able to accept electrons, form c=c, more rxns

50
Q

Transition state stabilization model

A

●AA residues within enzyme active site make the most contacts during transition state of rxn, so breaking bonds during rxn requires no direct input of energy by protein

51
Q

Transition state analogs

A

●tight binding of transition state analogs to enzyme active site- support transition state stabilization model
●definition: stable molecules that mimic proposed transition state, bind tightly to active site
●gets enzyme stuck??
●can have stronger affinity of enzyme for transition state analog than enzyme for substrate
●transition state has an molecule for the inbetween of reactant and product

52
Q

Acid-base catalysis

A

●proton transfer that either involves water (specific acid-base) or a functional group (general acid-base)
●arrangement of residues at active site -> enzymes can often perturb pKa values of functional groups to increase proportion of group in correct ionization state needed for chemical rxn
●Histine-> pKa 6 -> can be weak acid or weak base

53
Q

Covalent Catalysis

A

●nucleophilic group on enzyme attacks an electrophile center on substrate to form covalent enzyme- substrate intermediate
●nucleophile donates electron pair
●electrophile accepts electron
●sulfur in the right environment to let go

54
Q

Metal-ion catalysis

A

●metals used to promote proper orientation of bound substrates and can aid in redox rxn
●enzymes with tightly bound metal ions are called metalloenzymes
●Zn2+ lower pKa of water and facilitates formation of nucleophilic hydroxyl group that attacks the substrate (through metal-ion coordination bonds)

55
Q

Cofactors

A

●small molecules that aid in catalytic rxn within active site
●include inorganic ions (Fe2+, Cu2+, and Mg2+)
●iron and cu irons are often required for enzymes that perform redox rxns
●magnesium, manganese, and zinc are frequently used to help bind substrates or stabilize an intermediate or transition state
●holoenzyme: enzyme with bound cofactor
●apoenzyme: removal of cofactor

56
Q

Coenzymes

A

●enzyme cofactors containing organic components
●include vitamin-derived species such as NAD+ and FAD

57
Q

Prosthetic groups

A

coenzymes that are permanently associated with enzymes

Biochemistry I (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions