Cooperativity and Allosteric Regulation

Question 1

myoglobin type of protein

Answer 1

monomer

Question 2

hemoglobin type of protein

Answer 2

dimer of dimers (ab)

Question 3

hemoglobin subunits are _____ to myoglobin and derived from

Answer 3

homologous, same evolutionary ancestor

Question 4

origin of human o2 binding proteins

Answer 4

diversification of Mb/Hb by gene duplication

Question 5

Why are multi-subunit o2 proteins common across the tree of life?

Answer 5

evolutionary advantage conferred by cooperative switching between high + low affinity

Question 6

type of curve for myoglobin and why

Answer 6

hyperbolic, o2 storage

Question 7

type of curve for hemoglobin and why

Answer 7

sigmoidal, o2 transport

Question 8

cooperative phenomena involves interactions between binding sites of a given subunit and

Answer 8

other, equivalent binding sites in the structure

Question 9

allostery

Answer 9

protein must transmit the signal that another ligand has bound to affect a different portion of the molecule

Question 10

does mb have any allostery

Answer 10

no

Question 11

why can hb have allosteric effects

Answer 11

quaternary structure

Question 12

how does a polypeptide binding a ligand affect structure in hb

Answer 12

changes structure of another polypeptide to favor binding. communicates structural changes that allow both to bind ligand more efficiently

Question 13

tense

Answer 13

deoxy-Hb

Question 14

relaxed

Answer 14

oxy-Hb

Question 15

changes in structure bc of o2 binding

Answer 15

1. movement of F helix
2. breaks salt bridges between subunits
3. narrows cavity between subunits

Question 16

when does structure shift happen

Answer 16

after o2 binding to only one or a few subunits to pre-organize o2 binding sites in other subunits

Question 17

o2 binding pulls ____ closer

Answer 17

proximal His

Question 18

o2 binding shifts the _______

Answer 18

F helix position

Question 19

o2 binding _________ the heme

Answer 19

flattens

Question 20

_____ that ____ T state structure are broken in transition to R state

Answer 20

salt bridges, constrain

Question 21

in the sigmoidal curve, the same delta po2 gives

Answer 21

larger delta theta

Question 22

the sigmoidal cooperative binding curve is a hybrid btwn

Answer 22

two hyperbolic binding curves

Question 23

Monond Wyman Changeux (Concerted) model

Answer 23

binding of o2 to one or more subunits favors all or none transition from t to r state for all subunits, increasing o2 affinity

Question 24

slope (n) =

Answer 24

Hill coefficient degree of cooperativity

Question 25

n=1 Hill coefficient

Answer 25

normal binding

Question 26

n>1 Hill coefficient

Answer 26

cooperative

Question 27

n less than or equal to

Answer 27

number of protein subunits

Question 28

on the hill plot, the curve starts to act like hyperbolic curve at

Answer 28

very high or low po2

Question 29

anything that stabilizes T state relative to R state ____ affinity or activity of the population

Answer 29

decreases

Question 30

allosteric regulators of Hb

Answer 30

o2, h+, CO2, BPG

Question 31

Bohr effect equation

Answer 31

Hb(R) + H <-> HHb(T) w/ protonated hemoglobin

Question 32

H+ binding favors the _____ (____ o2 affinity) state

Answer 32

tense, low

Question 33

o2 and h+ are bound by Hb in an ____ manner, Hb tends to _____ protons upon binding o2

Answer 33

inverse, release

Question 34

does h+ interact directly with heme or oxygen?

Answer 34

no

Question 35

H+ changes the ________ of specific groups on the protein, especially

Answer 35

ionization, histidine

Question 36

Bohr effect in tissues

Answer 36

at the po2 in tissues, increasing H+ decreases the fractional saturation, driving o2 off Hb

Question 37

H+ binding favors _________

Answer 37

t state salt bridges

Question 38

why does His become protonated at ph 7.4 instead of 6.0

Answer 38

protein microenvironment

Question 39

high co2 content of respiring tissues

Answer 39

lowers o2 affinity decreases pH slightly increases h+

Question 40

when o2 is released by hb

Answer 40

co2 is converted into carbonate h+ is taken up by hb

Question 41

co2 affect on o2 affinity

Answer 41

decreases hb affinity for o2

Question 42

Co2 reversibly forms a _____ to _________, yielding ________

Answer 42

covalent bond, a-amino group at N-term of each of the 4 chains, carbamino-Hb

Question 43

which structure does co2 change favor

Answer 43

t state

Question 44

BPG is ______ at high altitude

Answer 44

upregulated

Question 45

BPG affect on affinity

Answer 45

decrease hb affinity for oxygen

Question 46

at higher altitude

Answer 46

more bpg, weaker o2 binding, more o2 released

Question 47

bpg binds ______

Answer 47

between hb subunits

Question 48

bpg charge

Answer 48

negative

Question 49

amino acids around bpg binding site charge

Answer 49

positive

Question 50

bpg equation

Answer 50

bpg*hb(t) + o2 <-> Hb(R)*o2 + BPG

Question 51

fetal erythrocytes contain

Answer 51

HbF

Question 52

HbF has _____ o2 affinity than HbA

Answer 52

higher

Question 53

variation in b chain that causes sickle cell anemia

Answer 53

glutamate to valine

Question 54

new ___________ between hemoglobin tetramers leads to _______ at low po2 in sickle cell anemia

Answer 54

sticky hydrophobic packing, aggregation

Question 55

what state is sickle cell anemia cells stuck in

Answer 55

t state, can't transport o2 efficiently