test 2: HB and Mb part 2 Flashcards
what is a protein family
evolutionaryily related proteins
globin fam
what does a hyperbola mean of cooperativity and sigmoidal
hyperbola = no cooperativity
sigmoidal = coopeativiity
what is the allosteric effect
binding at one site affects binding at others
how many subunits are required for allosterism
more than 1 subunit
what does the S curve indicate
allosterism
what is HOMOtropic allosteric interaction
effector and ligand are regulated by the same molecule
O2 and Hb
what is heterotropic allosteric interaction
effector and liganrd are differnt
what is an activator and what is an inhibitor
- activator shifts the eq toward R state= positive interaction
inhibitor shifts towards the T state meaning - interaction
descrube Hb oxugen affinity
starts out high but then FAVORS T state in the eq between T and R
what does BPg, h+ and co2 favor
tense low affinity
what are BPG,H+ and Co2 involved in
the Bohr effect
what does O2 favot
relaxed state
what is the bohr effect
- increased temp = release of O2 from Hb
- increase Co2, increase H+, increasing temp = release of O2 = decrease in affinity of H2
what happens to the curve if the affnity is decreased
curve shifts to the right
what happens withn
Temp increase
ph increase (basic)
co2 decrease
curve shifts to the left
how does temperature increase affect Hb affinity
high temp like fever will cause Yo2 to decrease wh
where on T state do Bohr protons bind
- N terminal amino gprps and His 146 betal
what amino group is responsiblel for 2-30% of the bohr effect
N terminal amino groups
what happens to the pka during transition
changes the pka causing them to release coordinated H
how much does his 146 account for bohr effect
40
what protons ar released when Hb binds O2
H+ protons
where on the T state does CO2 bind
-N terminal amino groups and it can form carbamates
- not present in the R state
what metabolism is O2 apart of
aerobic
oxidizing carbon cpds releases whawt
energy and O2 consume, CO2 is made
is Co2 soluble in plasma
nowhat
does cabonic anhydrase do
makes CO2 soluble by catalyzing the reaction
how does carbonic anhydrse relate to pH
helps buffer blood at pH of 7.4
how is carbonic anhydrase related to the bohr effecr
- increases H+ conc bc CO2 is converted to bicarbonate
- conformational changes stabilizing the tense (T state)
what do the lungs facor
decrease H+, increase in pH = lungs = R state
what do the capillaries favor
- T state
- high H+, low pH
what is the most abundant organic phosphate in blood
2,3 BPG and it is made in glycolysis
what does BPG do
- binds to T state and stabilizes it
- shifts equ. toward T STATe
can BPG bind to the R state
no it can’t
how is BPG helping with high altitude
- body increse BPG decreased pO2
- increase = more oxygen is being released to the tissues
what does BPG do to Hb
- gives Hb a p50 of 26 and without BPG it is 12 torr
- fine tines Hb O2 binding capability ( without it O2 delivery would be bad)
what other allosteric effector causes O2 to release
Cl-what
what is the role of Cl-
- netraulize the RBC electrosatic potential
- binds to doexy Hb( causes O2 release) = chloride shift
out of bPG, H+. CO2, Cl- and O2 what is the homotropic effector
O2
what is the hill equation
E + nS = Es
E= enzme
S= substrate
n = number of S mlcls bound
what does the farctional saturation ys =
bound total
n(Esn)/n(E+ESn)
what does the slope of the hill coefficient show
the degree of cooperativity
if n = 1. n>1, n<1
- n = 1 means non cooperative
n>1 means positive coop
n< 1 means negative coop
for Hb what is cooperative
n is close to 3
if 1 o2 binds…
the rest binds, and if 1 is released the rest are released
what is the concerted model for allosteric proteins
- eq between t and r states
- ligand bind to either conform
- ligand absent = T state
- binding of ligand shifts toward R state
what is a limiattion of the concerted model
only shows positive cooperativity
what is the induced fit model
- subinits can exits in T or R
- presence of R = increased affnity
- T to R is sequential process
- accounts for both + and - cooperativity
what are some effects of mutations on the protein
- inheritable or genetic diseases
- core of protein: affect the function and structure
how can mutations be good for Hb
- stabilize Metmoglobin like Hb boston
- Fe+3 form is stabilized = O2 binding eliminated
-cyanosis- blood is blue to chocolate brown
describe pathological mutaions at surface of Hb
- not as dangerous ‘
- Hbe( glu 26 on beta chains turn to lys) no effect
what can be a harfmul mutation
- Hbs sickle cell anemia Glu6 on beta to val
what is similar about HBs and HbA
- same O2 binding
- 4 hemes
iron in Fe+2
same active site
Hbs pathology
- E to V in beta chain making Hbs more hydrphobuc
- ONLY IN T STATE( val fits into the pocket )
linear polymers
what happens when Hbs loses O2
- Hbs starts to polymerize
- polymersization causes blood cells to sickle
- sickle = block capillaries and blood flow
benefit of hBS gene
- protection from maleria
