Term
|
Definition
*binding of one ligand at one site affects binding at another (coop binding)
*need interactions amoung subunits of oligomeric proteins
-allows ability of subunits to interact (depend on e.other)
*2 Models of Allosterism: symmetry, sequential
*(EX): Hb |
|
|
Term
| Symmetry Model of Allosterism |
|
Definition
*if ligand binding to R (oxy) is tighter than T (deoxy) = T-> R shift promoted
-shift increases affinity of unliganded subunits for ligand
-change in states = T ->R = inc affinity
*on/off (T or R)
R: bind tight
T: bind weak |
|
|
Term
|
Definition
1) AN ALLOSTERIC PROT IS AN OLIGOMER OF SYMETRICALLY RELATED SUBUNITS
-for valid, need to have oligomer w/ subunits
2) E. OLIGOMER CAN EXIST IN 2 CONFORMATIONAL CHANGES (T/R IN EQUIL)
-subunits need to be related
3) LIGAN CAN BIND TO A SUBUNIT IN EITHER CONFORMATION (WHICH DISPLAY DIFF AFFINITIES)
-allows back and forth
-oligomer has states (both need to bind to ligand)
-state have diff affinities
4) MOLECULAR SYMM OF PROTE IS CONSERVED DURING CONFORMATIONAL CHANGE
-symmetry stays in tact |
|
|
Term
| Problems w/ Symmetry Model |
|
Definition
1) all subunits in either T or R
2) symmetry not 100% preserved in all protein
3) model can count only for positive coop |
|
|
Term
| The Sequential Model of Allosterism |
|
Definition
*ligand binding induces conform change in subunit in which it binds
-e.ligand bind site is independent
-changes can occur ind on bind sites
*cooperative interactions on neighboring subunits
-but more flex than symm
*conform change occur sequentially as more bind sites are occupied
*ligand bind affinity varies w/ conformation
-proteins can be positive or negative coop (can inc or dec affin) |
|
|
Term
|
Definition
*effect structure and function
* >90% in 1000 variant Hb mutation from single AA sub
*5% carriers of gene |
|
|
Term
|
Definition
1) DESTABILIZE Hb 3*,4* STRUCT
-alter p50
-reduce cooperativity between subunits (inc/dec affin)
2) DEGRADATION BY ERYTHROCYTES
-products make eryth lyse = hemolytic anemia |
|
|
Term
|
Definition
|
|
Term
|
Definition
*compromised O2 delivery to tiss
*unsable Hb removed from blood circ b/c need to be replaced w/ func Hb -> reduces amount of O2 delivered |
|
|
Term
|
Definition
*ind have metheMb in arterial blood -> blue skin (mutation @O2 bind site, so cant bind O2)
*no Hb, so Fe in loose state
*Hill coeff 2 -> 1.2 |
|
|
Term
|
Definition
*inc affinity of Hb to O2
*low amounts of O2 released to tiss
SOLN: inc # of erythro |
|
|
Term
|
Definition
HOMO
*have deoxyHbS -> forms insoluble filaments -> deform erthro
*many carriers have only mild form (b/c high fetalHb w/ y chain rather than defective B)
HETERO
*w/ HbS = 40%: norm life, erythro shorter life
*sickles (elongated, rigid) cant pass through caps
-deoxination occur in caps
*blood flow to tiss blocked = necrosis (tiss death)
*if broken = hemo anemia
*mutation @ Glu 6 -> Val 6 in e.Bchain
-Val 6 in phobic pocket on surf of B subunit
-contact allows HbS tetramer form linear polymers
-strands aggregate and form fibers
*blood blockage sporadic
-poolymerization of HbS is time and [] depend |
|
|
Term
| Fetal Hb and Sickle Cell Anemia |
|
Definition
FETAL Hb DILUTES HbS
*less likely to form filaments
*make more diff for HbS to aggregate during transport from tiss -> lung for reoxygenation
*addding hydroxyurea increases fraction of fetal Hb |
|
|
Term
|
Definition
HETERO
*more resistant to malaria b/c less chances of sickling (better than homo Hb)
HOMO
*die in childhood w/o treatment
*P.Falciparum increases acidity of infected erythro (0.4 pH units)
-lower pH favors deoxyHb (Bohr)
-inc likelihood of sickling in HbS erythro
*damaged erythro removed by spleen so pathogen goes w/
*scikling mech disrupts parasite lifecycle
EARLY
*parasite enhances sickling allows spleen to remove infect erythro
LATE
*parasites attach to cap walls (so spleen does not remove) |
|
|
Term
|
Definition
| Striated- long multinucleated cells (musc fibers -parallel bundles of myofibrils- alternating thick/thin fila) |
|
|
Term
|
Definition
*striations caused by banded myofibril struct
*bands: alternating greater (A) and lesser (I) electron density
*sarcomere- myofibril repeat unit, bound by Z (center of e. I) |
|
|
Term
|
Definition
A: centerd on H; thick (150)
H: centered on M
I: thin (70) |
|
|
Term
|
Definition
*I & H reduce distance (up to 1/3)
*reduce length of sarcomere
*Sliding FM- thick and thin slide past e.other
DURING CONTRACT:
*muscle becomes shorter
*muscle become thicker
*total vol does not change |
|
|
Term
|
Definition
*thick filaments
*6 polypep chains (2HC, 2 pairs LC -> essential LC, regulatory LC)
*2 ahelical tails form Lhand coiled coil
*60-70% |
|
|
Term
|
Definition
N TERM HC (MYOSIN HEAD)
*binds 1 subunit of ELC and RLC
C TERM HC
*forms long fibrous helical tail
ROD LIKE TAILS
*bind end to end tightly
GLOBULAR HEADS
*project to sides on both ends (important for movement) |
|
|
Term
|
Definition
*globular heads bind actin
-form cross-bridge to thin filaments (between myo and actin)
*an ATPase
-ATP-binding site in V shaped pocket
-allows musc contraction
-APT Bound can be converted to E |
|
|
Term
|
Definition
*thin filaments
-most abundant cytosolic protein
*dont need ATP hydrolysis till later (orientation remains)
*20-25%
+ END
*thin bind to Z (pointed @ Z)
*give direction to sarcomere in thin
- END
*point toward M
*end of fiber where nucleotide bind sites open |
|
|
Term
|
Definition
G ACTIN
*monomer
*ATP bind site and Ca or Mg located in cleft
*can bind single myosin head (ION PAIRING, PHOBIC PATCHES)
F ACTIN
*polymer
*double stranded helix of subunits (e subunit has 4others)
*fiber has polarity |
|
|
Term
|
Definition
*contractile unit of musc cell b/c interacting myo and actin filaments
*orientation of actin, myosin reversed at M
*polarity same on both sides of sarcomere |
|
|
Term
| Proteins in Musc Structure |
|
Definition
CONTRACTILE COMPONENTS
*actin, myosin
THIN COMPOSITION
*tropomyosin
*troponin
THICK COMPOSITION
*Myomesin
*M-Protein
*Protein C
FORM Z & M/ ORGANIZE THICK AND THIN
*a-actinin
*titin
*nebulin
*tropomodulin
*CapZ |
|
|
Term
|
Definition
*homodimer
*2 a helical subunits wrap aroun e.other
*parallel coiled coil
*joined head to tail to form cables in F actin
*each molecule contains 7 consecutive actin subunits |
|
|
Term
|
Definition
*3 subunits
TnC: Ca bind subunit; Ca
TnI: binds to actin; actin
TnT: elongated molecule, bind to tropomyosin @ head-tail junc; tropomyo
MYO-PONIN COMPLEX:
regulates musc contract by controlling access of myosin heads to actin bind sites |
|
|
Term
|
Definition
*rod like, homodimeric
*cross links Factin filaments
*localized in Zdisk int
*attacth opposite thin fila to Z |
|
|
Term
|
Definition
*longest known polypep chain
*repeating domains
*3-6 w/ each thick fila |
|
|
Term
|
Definition
*large a helical
*associate with thin
*set length for thin by acting as template for actin polymerization |
|
|
Term
|
Definition
*caps - end of thin
-prevents further actin polymer/ depolymer |
|
|
Term
|
Definition
*AKA B-actinin
*a-actinin caps + end of F |
|
|
Term
|
Definition
*thick fila assembly
*bind to titin |
|
|
Term
|
Definition
*sex linked musc wasting disease
DUCHENE (DMD)
*2-5yr
*musc degen >> musc regen = progressive musc weakness
*death by 25 b/c resp disorder, heart failure
*no detectable dystrophin (rapidly degraded)
BECKER (BMD)
*5-10yr
*musc degen > musc regen = less progressive
*longer lifespan
*dystorhins of altered size (semi func) |
|
|
Term
|
Definition
*lrg protein low in quantity
*associate on in musc plasma memb w/ transmembrane glycoprotein complex
*anchor F acting to extracell matrix
*protects plasma memb tearns from stress of contraction |
|
|
Term
| Myosin Mediated ATP Hydrolysis |
|
Definition
1) ATP BINDS TO MYOSIN HEAD
2) MYOSIN ACTIVE SITE CLOSES AROUND ATP
3) MYO HEAD BIND WEAK TO ACTIN
4) MYO RELEASES Pi
5)POWER STROKE
6) ADP RELEASED, CYCLE AGAIN |
|
|
Term
| Myosin Mediated ATP Hydrolysis: Step 1 |
|
Definition
1) ATP BINDS TO MYOSIN HEAD
*inc Ca -> change in myo-ponin -> cause myo head actin bind site to open
*release bound actin
*ATP bind on site of myo head, actin bind site release previous bound actin (conform change of myosin head) |
|
|
Term
| Myosin Mediated ATP Hydrolysis: Step 2 |
|
Definition
2) MYOSIN ACTIVE SITE CLOSES AROUND ATP
*ATP bind site also at head (diff then actin bind site)
-ATP not released
*hydrolysis of ATP -> ADP+Pi (head cock)
-to make into available forms of E
-cause conformational change (releasing subunit of actin and moving towards plus side)
*high E conformation
*myo head perpendicular to thick fila |
|
|
Term
| Myosin Mediated ATP Hydrolysis: Step 3 |
|
Definition
| 3) MYO HEAD BIND WEAK TO ACTIN |
|
|
Term
| Myosin Mediated ATP Hydrolysis: Step 4 |
|
Definition
4) MYO RELEASES Pi
*release pyrophosphate, actin bind site close, myo bind towards actin (b/c inc affinity) |
|
|
Term
| Myosin Mediated ATP Hydrolysis: Step 5 |
|
Definition
5)POWER STROKE
*once myo binds -> power stroke
*moving attached thin F fila toward M
-myo remains, actin rope moving towards M
*ONLY MOVEMENT ON MYO HEAAD SO NO MUSCLE CHANGE YET |
|
|
Term
| Myosin Mediated ATP Hydrolysis: Step 6 |
|
Definition
6) ADP RELEASED, CYCLE AGAIN
*need to make sure binding sight can be occupied again so release ADP
*bind site empty, myo bound to new actin and start again w/ new ATP |
|
|
Term
|
Definition
Stimulate Myofibril:
*release Ca from SarcR at end of nerve -> intracell Ca inc -> conform change in myo-ponin -> myo head expose on actin |
|
|
Term
|
Definition
*troponin-tropo complex in rest conformation
*no bind of myo to actin (bind site block) -> musc relaxed |
|
|
Term
|
Definition
*forms microfilaments
*needed for cell shapes, cell division, endocytosis, organelle transport |
|
|
Term
|
Definition
1) ATP -Gactin binds (to both ends of F actin fila w/ greater affinity to + end)
2) Polymerization activates Factin subunits
-hydrolyze bound ATP
-slower than actin polymerization |
|
|
Term
| Microfilament Treadmilling |
|
Definition
+ END
*ATP subunits predominate
*subunits added
- END
*ADP subunits predominate
*net dissociation
STEADY STATE(same length):
*polymerzaion = dissocaition
*driven by free E from ATP hydrolysis
*IMPORTANT IN AMOEBAS, cell shape
*process driven by ATP bound by globular actins, hydrolyzed, polymerization at + @ higher rate than depolyerizzation |
|
|
Term
|
Definition
*activated= ATPbound molecule
*ATP bound actin (activated) so can polymerize on both +/- ens of F actin
* has higher affinity for + end so most ATP here
*(once bind hydrolysis of ATP bound to globulAR ACTIN)
*dissociation from - end so ADP
*hydrolysis slower than polymerization (so inc rate of growing) |
|
|
Term
|
Definition
*used in amoeba movement
*+/- end
*directional growth of actin fila w/ anchoring to cell surf
*TRAIlING EDGE( release contact w/ surf), LEADING EDGE (polymerizing)
*microfilament rearrange essential for neutrophil func |
|
|
Term
|
Definition
*recognizing patho or hazard that penetrates mucous memb
RESPONSE:
1) triggered by presence of foeign molecle (protein/ carbo)
2) B cells prod antibodies and display Ig on surface
3) antigen binds to matching Ig (have to match)
4) B cell engulfs antigen antibody complex, degrades frags , and frags displays on surface
5) T cells recognize fragments displayed so stim B cells to proliferate (secondary immune resp)-> b cells producing more |
|
|
Term
|
Definition
CELLULAR
*mediated by T cells (mature in thymus)
*responds to pathogens (but effective against viruses)
HUMORAL
*mediated by antibodies (Ig)
*antibodies prod by B cells (maturation in bone marrow)
*effective against bact and extracellular infection (virus) |
|
|
Term
|
Definition
*first response
*mark antigens for removal
*once B cell proliferate, start circulating and release antibodies and mark antigens to be removed from system
*circulating cells secrete lrg amounts of antigen sp antibody (bind to antigen)
-antigen marked for destruction by IS |
|
|
Term
|
Definition
*long liveed, only sm amount of B cels produced
*severe and immediate resp to recognized antibody
1st time antigen: little release of antibodies
2nd time: signficant release of antibodies |
|
|
Term
|
Definition
*spring
*response of body to chemicals in env that doesnt cope w/
*antibodies bind antigen and release histamine
*bind antigens for Ig for ragweed, second time bind release more |
|
|
Term
| Acute Exposure to High Altitude |
|
Definition
IN HIGH ALT, LOW O2 []
*inc hypoxic ventilatory response
*leads to inc sympathetic activity (heart rate, cardiac output, bloodpress)
*inc [Hb]
*decrease plasma vol b/c dec density (inc RBC)
*inc erthropoetin
*inc D-Dimer |
|
|
Term
|
Definition
*hyperventilate (dec CO2) -> hypercapnia -> resp alkalosis (O2 affinity inc)
*O2 curve moves to right in acclimation so more O2 can be delivered (dec affin) |
|
|
Term
| BPG and High Alt Acclimation |
|
Definition
ATM PRESS LOW
*need to maintain norm O2 delivery
*rapid inc in BPG (made in RBC) shift Hb O2 more right
-can now deliver more O2 (almost norm)
-dec of O2 bound to Hb
-inc of O2 released at tiss |
|
|
Term
| Chronic Exposure to High Altitude |
|
Definition
*polycythemia -> inc O2 carrying capacity of blood -> b/c inc in prod of erythropoietin
*inc RBC by secondary polycythemia
*natural or artificial inc in erythropoeitn (inc erythrocyte prod) |
|
|
Term
|
Definition
*inc # of erythrocytes
*inc # of Hb per erythrocyte
GOAL: improve athletic performance (inc erythropoietin w/o side effects)
*best done at minimum and temporary training |
|
|
Term
|
Definition
1) hyper coagulation
2) HbS carriers prob b/c cant take O2 to tiss -> lactic acid (dec pH) -> more in deoxy and cells more likely to sickle
3) athletes at risk for UV radiation
-UVA, UVB exposure inc chance of dermatitis, cataracts, cancer
4) poor sleep quality
5)loss of appetite (suppress DS to conserve E)
6) hypohydration(direness and dec fluid)
7)dec in glycogen storage deficit- diet mainly carbo |
|
|
Term
|
Definition
NOT AT RISK
*young athletes
*pregnant women (but living, have delayed uterine growth)
*older athletes (depend on healht) |
|
|
Term
|
Definition
*have constant and variable region
*four subunits (2 LC, 2HC =form Y (LH2)
*2 subunits associate by DiS(Cys) and noncovalent interact
-gives rise to subunit conformation
*prod by B cells |
|
|
Term
|
Definition
*differ in HC and sometimes subunit
IgA
*mono, di, tri, tetra/mers
*intestinal tract
*defend pathogens by adhere to antigenic site
*multivalent (can bind 2+)
IgD
*no known func
IgE
*sm [] in blood
*protect from parasites
*allergic rxn
IgG
*most common
*equally distributed between blood and extravasc fluid
*have diff AA seq to recognize antigen
IgM
*5 Y molecules around central J
-J subunit surround by L and HC
*most effective against microorg
*multivalent (can bind 2+)
*1st Ig secreted in resp to antigen |
|
|
Term
|
Definition
FAB FRAGMENT
*entire LC
*NTerm of HC
*IgG antigen bind site
Fc FRAGMENT
*CTerm of 2HC
VARIABLE REGION
*@ tip top
*responsible for antibody binding (antigen bind site)
*HC and LC e have variable/conserved
LC
*V(L) and C(L) region
*differ on NTerm
HC
*V(H) and 3 C(H) region (homologous to e.other)
-homologous to conserved region of LC so DiS bond hold together in Y |
|
|
Term
| Antibody- Antigen Interactions |
|
Definition
*VanderWalls, phobic, Hbond, ionic interact
*specificity and strength of antigen bind complex
-func of structural complementarity between antigen and antibody
*most Ig can bind 2 identical antigens simultan (multivalent)
-b/c foreign substance has multiple antigenic regions
*Immune Response generates micture of antibods w/ diff specificities |
|
|
Term
|
Definition
*allows antibodies to cross link antigens
-form extended network/ lattice
-allows speed of recognition/removal of antigen
*hasten removal of antigen
*triggers B cel proliferation |
|
|
Term
|
Definition
APPLIED IN
*ELISA
*Purify macromolecules
*identify infectious disease
*test presence of drugs and other subs in body tiss
*therapeutic agents against cancer/ disease
(EX): Breast Cancer
*HER2= overexpressed growth factor
*block HER2 by bind herceptin (stop growth) |
|
|
Term
|
Definition
1) essential components in lipid bilayer (bio memb)
2) E storage (hydroC chain)
3) cellular signaling |
|
|
Term
|
Definition
*determined by length and saturation of FA chain
*soluble in organic solvents
*easily separated from bio materials by extraction into organic solvents
*(EX): fats, oils, some vitamin/horm, most nonprotein emb components |
|
|
Term
|
Definition
*carboxyllic acid w/ long chain hydroC side groups
*usually C16, C18
*UNCOMMON: <14 or >20 Catoms
*even number of Catoms (b/c biosynth by concatenation of C2 units)
*1n - 9: # of double bonds + location)
UNSATURATED
*more 1/2 FA of plants, anim
*double bonds w/ cis config
*most are polyunsat
*less efficiently packed together
*MP dec w/ degree of unsat of doub bond
*no free rotations
SATURATED FA
*highly flex
-can assume lots confomrations b/c free rotation
*MP inc w/ molecular mass (length)
-more C = inc MP
*no double bonds (no rigidty) |
|
|
Term
|
Definition
*made up of glycerol w/ C w/ diff FA associated
-glycerol w/ 2-3 esterfied FA
*H2O insoluble
*High E reservoirs
*most abndant class of lipids
*vary based on placement of 3 FA residues
*named by placemnt of glycerol moieties (Cchains) |
|
|
Term
|
Definition
*both mitures of TGs
FATS
*soild at room T
*efficient way to store metabolic E
OILS
*liquid at room Temp
*plant oil richer in unsat = lower MP |
|
|
Term
|
Definition
*less oxidized than carbo/proteins
-yield more E per unit mass (after oxidation)
-can deliver more O2
*nonpolar, stored in anhydrous form (no H2O)
-glycogen binds 2x amount of weight in H2O
-glycogen is bind more H2O than TG
* metab E in fats 6x > hydrated glycogen |
|
|
Term
|
Definition
*used for TG synth/ storage
*entirely filled w/ fat globules
*fat reservoirs (allow to live w/o food)
*thermal insulation in subcutaneous (need for warm blood in low T) |
|
|
Term
|
Definition
*AKA glycerophospholipids
*major component of bio memb
*have glycerol-3P
-w/ C1 and C2 esterfied w/ FA
*have phsphoryl group
-linked to polar group
*ampiphilic (diff platiy on head and tail)
-nonpolar alipathic hydroC tails
-polar phosphoryl-X heads
*simplest are phosphatidic acids (only in sm amounts) |
|
|
Term
|
Definition
HEAD GROUP
-from polar alcohools
C1 POSITION
-sat C16/C18 FA
C2 POSITION
-has unsat C16/C20 FA
*names according to identity of FA
*chem struct determined based on hydrolytic rxn products |
|
|
Term
|
Definition
*enz catalyzes hydrolysis of PGs
(EX): phospholipase A2
*excises FA @C2 -> leave lysophospholipid
*lysophospholipid- powerful detergent cause cell lysis; aid in lipid diestion
*hydrolyze and release FA at A2
*A2 acts on FA @C2
*in bee and snake venom |
|
|
Term
|
Definition
*if PG not fully hydrolyzed = become signal molecule
Lysophophaditic acid (LPA)
*prod by hydrolysis of memb lipids in blood plateletss in injured cells
*stim cell growth as part of wound repair
1,2 diacylglycerol
*ativates kinase
*derived from memb lipids by action of phospholipase C |
|
|
Term
|
Definition
*glycerol > TG > Plasmologens
*type of PG
*C1 has glycerol; ether link a,B unsat (cis) |
|
|
Term
|
Definition
*sphingosine > ceramide
*derivatives of C18 shingosine (double bond in trans)
*has parent component (ceramide)
TYPES:
sphingomyelins
cerebrosides
gangliosides |
|
|
Term
|
Definition
*have Nacyl FA deriv (ceramide)
*C18 amino alcohol |
|
|
Term
|
Definition
*Nacyl FA deriv
*parent compounds of sphingolipids |
|
|
Term
|
Definition
*TYPE OF SPHINGOLIPID
*most common SL
*has ceramide w/ PCholine or PEthanolAmine
*10-20 plasma lipids
*sim conformation as phosphatidylcholine but dif chem
-glycerol back, head, tail= diff (charge distrib =same)
*myelin sheath (insulate nerve axon)
-high lipid content = electrical insulator |
|
|
Term
|
Definition
*TYPE OF SPHINGOLIPID
*head group w/ single sugar residue
*Galacto"" and gluco"" most prevalent
*nonionic = lack phosphate groups |
|
|
Term
|
Definition
*TYPE OF SPHINGOLIPID
*most complex glycosphingolipid
*ceramides w/ attached oligosach
-have at 1+ sialic acid residue
*sialic acid + sugar residue
*important for brain func
-carbo head receptor for pit glycoprotein hormone ad bact toxins
*on cell surf memb |
|
|
Term
|
Definition
STEROID
-cholesterol
ISOPRENOID
-coenz Q
-Vit A
-Vit D
-Vit K
-Vit E
EICOSANOID
-Prostaglandin
-Thromboxin
-Leukotrienes
-Lipoxins |
|
|
Term
|
Definition
| *compound w/ 4 fused nonpolar rings |
|
|
Term
|
Definition
*sterol b/c C3-OH
*27C
*methyl @ C10, C13
*contrib to viscosity of lipid bilayer
*in anim plasma memb
*most abundant steroid in anim
*weak amphiphilic
*greater rigidty => fused rings
*precursor to steroid hormone |
|
|
Term
|
Definition
PLANTS
*little chol = syth other sterols
YEAST/FUNGI
*cholesterol differ (# aliphatic SC and double bonds)
PROKARYOTES
*little/no sterol |
|
|
Term
|
Definition
*regulate physiological func
*classified according to response evoke
*H2O insoluble
*bind to proteins for transport through blood to target tiss
TYPES
1) Glucocorticoid
-cortisol
2) Mineralocorticoid
-aldosterone
3) Andro/Estro-gens
-testosterone, B-estradiol
4) Sterol Dervative
-Vit D |
|
|
Term
|
Definition
* (EX): cortisol (C21)
*affect carbo, protein, lipid metab
*influence vital func
*no OH on C3
*SYNTHESIS: by cortex (outer adrenal) |
|
|
Term
|
Definition
*(EX): Aldosterone
*reg kidney excretion of Na & H2O
*SYNTHESIS: by cortex (outer adrenal) |
|
|
Term
|
Definition
*(EX): testost (C19) ,B- estradiol (C18)
*affect sexual development and func
*estrogens have aromatic ring
*SYNTHESIS: by testes/ovaries (sm #s by adrenal) |
|
|
Term
|
Definition
*(EX): Vit D
*disrupted B-ring between C9-C10
*water insoluble
*accumulates in Fatty tiss
*too much = Vit D intox
*formed enzymatically (in anim skin/ UV light on plant sterol ergosterol in milk)
-can put in active form w/ UV light
*active VitD promotes intestinal abs of Ca (inc serum [Ca]; inc Ca in bone/teeth
-inc in serum: calcification of soft tiss & kidney stones 9b/c H2O insoluble)
*enz hydroxylation liver (@C25) and kidney (@C1)
*contribu to skin pig
-inc closer to equator
-filters solar rad to prevent intox
-solar radiation prevents VitD intox |
|
|
Term
|
Definition
R=X
* 7 dehydrocholesterol -> cholecalciferol (D3)
R=Y
* ergosterol -> ergocalciferol (D2)
**to put in active form, use enz hydroxlation (add OH)**
* D2/D3 -> 1a,25 dihydroxycalciferol |
|
|
Term
|
Definition
*soluble in lipid bilayer (fat soluble: VitD)
*not structural part of memb
*built from C5 units
*same CSkeleton as isoprene
*plants are rich in isoprenoid compound
-pigment, horm/pheremone signal, defensive agents
(EX):
coenz Q; Vit A,D,E,K (vitamins req in sm amounts & not synth in body) |
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Term
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Definition
*reversible red and oxid in mito memb
*10 isoprene units |
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Term
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Definition
*AKA retinol
*plant prod deriv (Bcarotene)
*deficiency -> blind
*oxidzed -> retinal (aldehyde)
*RETINAL- eye photoreceptor in low light
*RETINOIC ACID- stim tiss repair, treat acne/ulcers, no wrinkles |
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Term
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Definition
PHYLLOQUINONE
*K1
*synthesized by plants
MENAQUINONE
*K2
*synth by bact
*mostly supplied by intestinal bact
*does carboxylation of Glu of blood clot protein
-deficiency = no carboxy -> inactive clotting proteins & excessive bleed |
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Term
|
Definition
*a-tocopherol components
*highly phobic
*in cell memb -> antiox prevent/repair oxidative damage to memb |
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Term
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Definition
*C20 compounds
*act at low []
*pain/ fever, reg blood press/coag, reg repro
*act locally (not in blood)
-b/c need to get to pain fast (rapid resp)
-decompose fast (limit effects on close tiss)
*arachidonic acid = precurssor
*(EX): PG, prostacyclins, thromboxanes, leukotrienes, lipoxins |
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Term
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Definition
*polyunsat FA, 4 double bonds
*stored in cell memb as C2 ester (phosphatidylinositol)
*FA residue released by action of phospholipaseA2
*metab = tiss depend
*aspirin inhibits PGhydroxyl @ PGH2 synthase |
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Term
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Definition
| *lipids associate w/ lipids -> miscelles/ bilayers -> memb basis |
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Term
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Definition
*globular
*phillic/ phobic areas -> form ellipsoidal/ spheroidal
-HydroC group not contact w/ H2O; phobic tails
*triangular (envelope) vanderwalls force
-eliminate contact between H2O and tails
-permits solvation of polar head
*single tailed (can aggregate closely), amphiphilic
-w/ longer tails, need more molecules
*# cells dictated by molecule nature
TOO FEW
*expose phobic core to H2O
*cant close circle
TOO MANY
*give hollow center w/ H2O (energetically unfavored)
*hole between FA
LARGE CELL
*flatten and rid of hollow center
*dec of curve at flat surface -> empty spaces |
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Term
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Definition
*(EX): Glycerophospholipids/ Sphingolipids
*retangular vanderwalls force (pack tighter)
*tais packed together -> form PMemb
*form lrg disk micelles = leaflet (liposomes) |
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Term
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Definition
*2 tailed micelles (form 1 bilayer)
*formed b/c suspension of phospholipids
*closed, self anneal, solvent filled
*uniform size
*stable
*purified by: dialysis, gel filt, centrifug
*can fuse w/ plasa memb to be abs
-good for drug delivery
(EX): DRUGS
1) introd drugs and use delivery syst for cells
2) Break bilayer add dru-> liposome anneals -> fuse w/ bio memb |
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Term
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Definition
TRANSVERSE
*flip-flop (rare)
*hydrated polar head needs to pass through anhydrous core (so op polarity)
*takes several days
LATERAL
*pairwise exchange of molecules in same leaflet
*lipids highly mobile in 2D fluid bilayer (common)
*permanent movement of memb components (molecules moving back and forth)
*not steady
*fast- 1sec |
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Term
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Definition
*ability of C-C bonds of lipid tails to rotate
-allows constant motion of bilayer interior (light machiene oil)
*inc closer to lipid heads
-b/c rotation head limited
-lateral movemnt controlled by other heads |
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Term
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Definition
*10-40C
*bact/ cold bood modify FA compositions of lipid (maintain constant fluidity)
BILAYER COOLS
*below TT
*gel like solid
*dec fluidty
*thicker bilayer
BILAYER WARM
*above TT
*inc mobility of lipid tails
-tails active move so inc distance between them
*lipid crystal
-lipids ordered in some directions, not in others
INC w/
*chain length of FA
*degree of sat of FA |
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Term
| Cholesterol as a plasticizer |
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Definition
*NOT form a bilayer
*decreases membrane fluidity, Inc memb rigidty
-rigid struct intereferes w/ FA SC move
*inhibits ordering of FA SC (fit in between them and stops others from moving around)
-broaden TT range of the phase transition
*stops free motion of FA |
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Term
| Membrane Protein Varieties |
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Definition
MYELINATION ON NERVE
*insulation so = dec protein
*19% pro
PLASMA MEMB
*50% pro by mass
INNER MEMB MITOCHON
*b/c xchange of intracell components
*76% |
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Term
| Membrane Protein Function |
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Definition
MAIN FUNC
1)CATALYZE CHEM RXN
-function as enz
2) MEDIATE FLOW OF NUT AND WASTE ACROSS MEMB
-flow into cell and waste out
3) FACILLITATE TO RELAY INFO FROM EXTRACELL ENV -> ITRACELL COMPO
-move info
OTHER FUNC
4) FUNC W/ LIPID BILAYER
5) INTERACT W/ PHOBIC CORE/ POLAR SURFACE
6) CLASSIFIED BY MODE OF INTERACT W/ MEMB |
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Term
|
Definition
INTEGRAL (INTRINSIC)
*tight association (b/c phobic rxns)
*separated from memb by SDS etc (strong detergent agents that disrupt memb)
-SDS solubilize memb protein by replacing norm memb lipids around them
-would have to move all lipids around them
-takes away charge
*important for molecule transport
*EMERSED IN NP INTERIOR: phobic surf residues
*EXTEND AQ ENV: sheather w/ polar
TRANSMEMBRANE
*(EX): glycophorin A, bacteriorhodopsin
*3 domains
-EXTERNAL (out cell):carbohy chains, NTerm side
-SPANS (in memb): phobic b/c interior; span memb
-CYTOPLASMIC (incell): CTerm (so compatible w/ aq phase), charged and polar
*important for signal transduct -> signal need in and out
PERIPHERAL
*(EX): CytC
*can dissociate from memb by mild detergent procedure and leave memb intact
*dont bind lipids
*purified -> behave like H2Osoluble protein
*bind @ memb surf
-electrostatic/ Hbond interact |
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Term
|
Definition
MEMBRANE PROT
*only one side of memb (either int or ext)
TRANSMEMB POT
*one direction w/ respect to memb (direction always same w/ CTerm in)
*NO PROTEIN OCMpleTEly BURIEd IN MEMB
-always a portion exposed to aq env |
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Term
| How transmemb SPAN bilayer |
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Definition
1) NEED PHOBIC SC THAT CONTACT LIPID TAILS
2) MUST SHIELD POLAR BACKBONE GROUPS
-must facilitate embedding of polar residue in memb
-does this by forming 2* struct (a,B)
-allow protein to shield phobic in |
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Term
|
Definition
*protein forms a helices --> barrel
*APase = gen ATP w/ H or proton grad (light driven)
*how 2* struct facil memb embed (spans whole memb)
*binds retinal covalent |
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Term
| 3D Struct of integral proteins |
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Definition
*H2O soluble -> needs to be protected
*stabilized by exclusion of int resid from surrounding solvent
*phobic effect main stabilizer 3D struct
*TM regions on integral proteins immersed in NP env |
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Term
|
Definition
*a helix/ antiparallel Bsheet forms to satify Hbond potential of seg in NonP memb
*many aggregate and form barrel
-B: # must be even 8-22(so can tight close on itself)
*(EX): porin |
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Term
|
Definition
*channel forming proteins in outer memb of Gram - bact
*out memb protect from hostile env
-porins allow sm polar solutes (nut)
*in outer memb mito & chloro(euk)
*transport in and out
*HELPS UNDERSTAND EVOLUTION |
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Term
|
Definition
*lipids covalently attached
*anchor protein to memb
*lipid group mediates prot-prot interact
*lipid group modify struct/ (func)act of prot
*3 varieties (prenylated, FAcylated, GPI)
-can have more than 1 group in a protein |
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Term
|
Definition
*have covalently attached lipids built/linked w/ isoprene
*COMMON: farnesyl (C15), geranylgeranyl (C20) |
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Term
|
Definition
*linked to memb proteins (have 2 kinds)
MYRISTIC ACID
*rare (sat, C14)
*MYRISTOLATION= stable
-faCYL remains intact for protein life
*link to protein by amide link @ amino group on NTerm Gly
*found in subcell compart (cytosol, ER, plasma memb, nuc)
PALMITIC ACID
*palmitoylated protein (palmitoylation)
-sat C16 FA palmitic acid join thioester link to Cys residue
*found on cytoplasmic face of plasma memb
*facilitate transmemb sig
*not as stable -> palmitoyl group can be removed (b/c thioesterase)
*reversible palmitoylation: reg associate of protein w// memb = modulate signaling |
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Term
Glycosylphosphatidylinositol-linked protein
(GPI-linked protein) |
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Definition
*in all euks (but abund in parasite protozoa)
*only on exterior plasma memb
*struct:
PHOSPHOETHANOLAMINE
*links to core @ amide group on CTerm carboxyl group
CORE TETRASACH
*linear
*3 mannose & 1 glucosaminyl
*Mannose @ nonreducing end forms phosphodiester w/ phosphoethanolamine
PHOSPHATIDYLINOSITOL
*glycosidic link w/ core tetrasach
*glycerol back, 2FA, phosphate |
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Term
|
Definition
*RBC (membranous bag of Hb allows transport of O2)
*model for studying memb struct/comp
-obtain by osmotic lysis
*shape maintained as moves across memb
*why used:
-easily isolated
-lack organelles (very simple)
-few metabolic process |
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Term
|
Definition
*cause leak of cell content
*remove content of erythro + obtain erythrocyte ghost
-put erythro in diff [Na]s
-if low Na in eryth, put in hypotonic -> cell swell/ explode
-all content released ->self anneal
-becomes colorless b/c everything in removed (maintain RBC shape but no cytoplasm) |
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Term
|
Definition
RIM REGION
*not in fixed position on memb
DIMPLE REGION
*not in fixed position on memb
*allows Hb to be close to surf at any time and easy acces to O2 (molecules always moving)
BICONCAVE DISC
*ensures rapid diffusion of O2 to Hb molecules
MEMB SKELETON
*submembranous network of proteins
*spectrin, (a,B); ankyrin
-can be found in other memb too |
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Term
|
Definition
*75% of skeleton
*composed of 2 sim polypep chains (a,B subunit)
-e. subunit has repeatin 106 residue seg -> fold into triple strand a helix coiled coil
-a, B loose wind and form a coil & then 2 wind around others, aB2 tetramer (provides ability to link other skeletal proteins)
*dimer link at heads to e.other; tetramers link @ end to other proteins
*form dense, irregular protein mesh in erythro memb
*help maintain shape and help erythro pass through caps
*if removed -> hereditary spherocytosis |
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Term
| Hereditary Spherocytosis (HS) |
|
Definition
*defect/ deficiency in spectrin
*erythro = spheroidal, fragile, inflex
*causes anemia b/c erythro lysis and removal of spherocyte cells by spleen |
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Term
|
Definition
*associated w/ spectrin
*binds to integral memb ion channel protein
-anchor memb skelton to protein |
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Term
| Asymmetric Distribution of Proteins |
|
Definition
*lipid/protein not in equal proportions on either side
*use enz (phospholipase) to see whats on what side of memb
-phospholipase cant pass, so only acting on phospholipid on exterior memb |
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Term
|
Definition
EUKS
*by integral memb protein
*of the ER
*lipids fabricated on site
PROKARY
*by integral memb protein
*in plasma memb |
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Term
| Lipid Labeling Experiment |
|
Definition
|
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Term
| Phospholipid Flip-Flop Facilitation |
|
Definition
FLIPPASES
*No E/ATP
-catalyze flips for specific phospholips
*facilitated diffusion
-equilibrate distrib of phospholips
-high -> low []
PHOSPHOLIPID TRANSLOCASES
*Need E/ATP
-transport specific phopholips across b/c ATP hydrolysis
*form of active
-move against gradient
-lower [] -> higher [] |
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Term
| Phospholipid Distribution |
|
Definition
COMBO OF
1) memb orientations of enz that synth phospholips
-location of enz
2) ATP dependent phospholip translocases
-activity of ATP
3) flippases
-activity of flippases |
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Term
|
Definition
*generated by expansion of existing memb
*lipds in euks synthesized on cytoplasmic face of ER
-transported to other parts of cell by memb vesicles from ER
-facilitated transport and maintenance of phospholi |
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Term
|
Definition
*lipid & protein arrangement
-allows to have distinct domains (diff func)
-doesnt have to be uniform mix and still has microdomains w/ enrich protein/lipids |
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Term
|
Definition
*come from specific interact of integral prot and specific lipids
*divalent metal ions (Ca2+) cause clustering (anything w/ op charge)
-bind to - lipid head
-interact between lipid and protein
*(EX): Lipid Raft |
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Term
|
Definition
*closely packed glycosphingolipids and cholesterol (need combo to work)
*floats and changes location
*see more crystalline struct
*more resistant to solubilization (detergents)
*can diffuse laterally w/in memb
* 1) platforms for assembly of complex intracellular signaling syst 2) can []prot & lipid in specific location
GLYCOSPHINGO
*cannot form layer alone
*in outer leaflet of plasm memb
*LRG head groups
-prevent close pack of sat, phobic tails
*associate laterally
CHOLESTEROL
*cannot form layer alone (b/c sm head)
*occupy voids between sphingo tails |
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Term
|
Definition
MEMBRANE PROTEIN
*synth by ribo
*do not change orientation after syth
-has a distinct direction (doesnt flip)
*grow from N->CTerm by stepwise addn of AA
RIBOSOMES
*free in cytosol or bound to RER
*FREE: synthesize soluble proteins & mito proteins
*BOUND: synthesize transmemb, secretion, ER operating, lysosome incorporated proteins |
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Term
|
Definition
*refers to bound ribosomes
*facilitating passage of lrg polar molecule through RER
-needed for polarizing proteins to cross memb
-40% protein synth need to be sec
@ER → cis golgi → stepwise relocation through golgi or can stay and move in lysosome →protein in lysosome @ trans → secretion
**all occurs inside vesicle until fuses w/ plasma memb and secreted |
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Term
| 7 Steps of Secretory Pathway |
|
Definition
1) POLYPEP SYNTH BEGINS (SIGNAL PEP)
-act of SRP (recognizes signal pep and bind to ribo and sig pep)
-start @RER and SRP in cytosol bind to GDP
-have SRPRecep and translocon (allows relocation protein through memb)
-ribo and mRNA work together to start synth (protein has signal pep to determine if secreted etc)
2) INHIBTION OF POLYPEP SYNTH
-receptor and translocon create pause in protein synth
-receptor and SRP removed
3) DIFFUSION OF POLYPEP-RIBO COMPLEX TO RER SURF
-ribo complex relocate toward memb
-translocase of protein & sig pep
4) POLYPEP SYNTH CONT
5) POLYPEP (PREPROTEIN) ENTERS ER LUMEN WHERE SIGNAL PEP GETS REMOVE
-sig pep cleaved (sec)
-stuck in memb (transmemb)
6) FOLDING/ POSTTRANSLATOINAL MOD OF NASCENT POLYPEP
-modify external by add carbo
-protein grows and modifies
7) POLYPEP RELEASED
-ribosome dissociates and goes back to start new synth |
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Term
|
Definition
*aq trans memb channel
*channel forming component of heterotrimeric protein (Sec61, euks; SecY, pro)
-very conserved b/c in all organisms
*facilitates passage of soluble proteins through memb
-uptake of sig pep
*facilitates insertion of TM segment of integral proteins into memb
-inclusion of TM into memb |
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Term
|
Definition
CAN BE CLEAVED
-meaning secreted (protein released)
OR INSERTED INTO MEMB
*meaning anchored to exterior
*very conserved struct across species |
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Term
|
Definition
*further processing of protein
*3 stacks of flat membraneous sacs (cis, medial, trans cisternae)
-e. has diff glycoprotein processing enz
*from cis -> trans mod in stepwise manner
CIS
*protein start; close to mnucleus
*take up new synth proteins
MEDIAL
*protein maturing...
TRANS
*protein exit to final destination
*suit nature of protein released
-mature proteins havediff sig pep to determine desired location |
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Term
| Mechanism of cis -> trans Golgi transport |
|
Definition
FORWARD (ANTEROGRADE) TRANSPORT
*w/in membrane vesicles
*stacks move forward
*from one stack to next (cis -> trans)
*req sep vesicle to be transported to diff layers
-vesicles move between sacs
*retrograde = backwards
CISTERNAL PROGRESSION (MATURATION)
*carried as passengers of Golgi compartments
*vesicle transport
*cis cisternae become trans cisternae
*proteins remain in sacs and moving through layers
-maturation of protein and sacs |
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Term
|
Definition
*preserves orientation of TM protein
*allows to transport protein to diff location (tagged by signal peptide)
*lumen of ER and Golgi cisterna -> out cell
-why carbo and GPI located out
*3 types (Clathrin, COPI, COPII)
*all have receptors bind proteins being transported
*all have proteins that mediate fusion of vesicles w/ target memb
-transport between regions (bud from origin and fuse w/ target) |
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Term
|
Definition
*forms polyhedral framework (network around vesicle)
*surrounds TM, GPI-linked, and secreted proteins
*from Golgi -> plasma memb
*proteins providing stability
*in endocytosis
*composed of triskelions (3 lrg/HC, 3 sm/LC) -> form polyhedral cages
-solid stable struct to surround vesicle |
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Term
|
Definition
*forms fuzzy coat
*vesicles carry anterograde/retrograde between successive golgi compart
*return escaped ER prot from GOLGI -> ER
-if process proteins and need them returned to earlier regions (need proteins in ER) |
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Term
|
Definition
*forms coat w/ 2 cosnerves heterodimers
*encodes vesicles transport proteins from ER -> GOLGI
*vesicle returned from ER -> golgi (back by COPI vesicle) |
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Term
|
Definition
*from expansion of existing memb (nonspontaneous)
-(EX): vesicle trafficking (euks)- vesicle buds off from 1 memb and fuses to other
*ensures lipid and protein transferred from parent to target memb
-so vesicles transport to sp places to embed |
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Term
|
Definition
1) NEUROTRANSMITTER
2) BIOLOGICAL MEMB FUSION
-SNARES |
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Term
| Neurotransmitter Transport |
|
Definition
1) small molecules released by neurons
2) nerve impulse in presynaptic cell reaches synapse
3) cause fusion of synap vesicles (w/ NT) and presynap memb
4) release NT in synap cleft
5) BT diffuse across synap cleft
6) NT bind @ specific receptors in postsynaptic memb
7) cont nerve impulse/ musc conract in post synap cell |
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Term
|
Definition
*memb dont fuse spontaneously
-repel e.other b/c - charge (need to overcome)
*proteins mediate vesicle fusion w/ memb = SNARES (integral/ lipid inked)
-SNARES facilitate memb fusion
*interact between Q&R anchor vesicles to target membm = docking (brings close together)
-Q/R together allow docking
*driven by trans-SNARE
R SNARE
*Arg residues
*associate w/ vesicle memb
Q SNARE
*Gln residues
*associate w/ target memb
**faster in body than in lab (vitro) b/c other proteins also assist in fusion ** |
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Term
|
Definition
1) form ring of SNARE complexes
-layers pulled together by mech force
-docking
2) contracting lipids and outer leaflets join (hemifusion)
-no aq contact yet
3)fusion proceed
-trans-SNAREs zip up
-new bilayer being formed
4) Induction of lateral tension
-form fusion pore
5) Rapid expansion of fusion pore
-sec of contents in vesicle
-2 memb and contents fully joined
-once fused, pull apart and release |
|
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Term
|
Definition
*org coordinate activities
-cells communicate w/ eother
*always have receptor protein, & mech for transmit ligand bind event to interior cell, & series of intracell response
-need recep proteins to recog ligand and signal from exterior cell and relocate across memb
*involve enz cascade (amplify signal) |
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