Globular Proteins Flashcards
what gas does hemoglobin trap
oxygen
heme is protoporphyrin with
iron in it
structure of myoglobin
8 alpha helixes
heme is placed b/w what segments of myoglobin
F & E
iron and oxidation
If iron Fe2+ is oxidized to Fe3+ it will no longer be able to bind oxygen
when iron is oxidized what happens
it disables the heme
myoglobin function
storage device for oxygen
hemoglobin function
has to pick up and deliver oxygen efficiently
how does hemoglobin pick up oxygen and deliver it efficiently
at high O2 pressure it has high affinity for O2, at low pO2 it releases O2 - has low affinity for it
hemoglobin structure
mixture of polypeptide
alpha and beta
4 globin chains
how is hemoglobin sequence different from myoglobin
myologin has proximal His and distal his
oxyhemoglobin
iron perferclty in plane of heme
when oxyhemoglobin
open door for heme to bind oxygen
in tissues what happens to iron group to release oxygen
proximal his is used as a leash, protein can change conformation and when iron is moved out of plane of heme then oxygen is released
hemoglobin is wht kind of protein
allosteric
what is allosteric protein
what is it in regards to hemoglobin
binding of a ligand to one site affects the binding to other sites
for oxygen binding to hemoblogbin - has four sites
binding of oxygen to one subunit affects binding to others
what is homotropic
The normal ligand of the protein is the allosteric regulator.
what is heterotropic
A different ligand affects binding of the normal ligand.
in regards to allosteric protein binding it can be
positive or negative
cooperativity is what kind of regulation
positive homotropic regulation
does myoglobin have cooperativity
no
does hemoglobin have cooperativity
yes
if you increase the pressure of oxygen what will happen to conformation of hemoglobin
it will increase the binding of hemoglobin to oxygen
if O2 levels are low what happens to affinity of hemoglobin and oxygen
it has low affinity so it can release the oxygen in the tissues
low affinity state of hemoglobin is called
t state
t state stands for
tense state
does t state ever happen
not in reality, its just in theory
what happens in t state
low oxygen affinity
binding of oxygen to one subunit in heme does what
increases affinity of the other, so oxygen can more easily bind another heme group
what does r state stand for
relaxed state
cooperativity of oxygen binding derives from
conformational changes in tertiary structure of each globin chain
conformational change from t state makes it become
r state with higher afinity
binding of 1st oxygen has what rate
its low - b/c energy needed to make first adjustment in conformation
what is the state with low affinity for o2
t state
what is the state with high affinity for o2
r state
describe properties of t state
Low oxygen affinity
Resists the binding of oxygen
Deoxygenated
More salt bridges
describe properites of r state
High oxygen affinity
Binding of oxygen is facilitated
Oxygenated
Fewer salt bridges
describe the middle of hemoglobin in structure of t and r state
the middle of t state looks more open the middle of r state looks more close
what are the three ways hemoglobin binding for oygen is decreased
- low pH (Bohr effect)
- binding of 2,3 bisphosphoglycerate
- covalent attachment of carbon dioxide (CO2)
Co2 gets hydrated and produces
carbolic acid
carbolic acid produces
more hydrogen and lowers ph
what does co2 do in regards to ph
it lower ph
how does co2 affect oxygen
it lowers ph which decreases binding for oxygen
2,3 bisphosphoglycerate - what is it
conjugate base
if ph is increased what happens to affinity for oxygen
it increases
what is ph of blood in lungs
7.6
what is ph of blood in tissues
7.2
if ph is decreased what happens to affinity for oxgyen
it decreases
what is bohr effect
describing how ph affects affinity for oxygen
one waste product of tissues is
co2
draw reaction of CO2 with water
CO2 + H2O ↔ HCO3− + H+
carbonic anyhydrase does what
decreases ph of cell
what does H+ do to hemoglobin
it binds to hemoglobin and stabilizes the T state
how does hemoglobin act as buffer
H+ can bind to it
draw out bohr affect, list all the steps
pg 15
histidine does what
accepts the proton and is protonated - when it is protonated it interacts w/ carboxylase an allows other reactions to occur → more salt bridges than in the Hb R state
2,3-bisphosphoglycerate is an acid or base
acid
what form is 2,3-bisphosphoglycerate present in body
conjugate base
what produces 2,3-bisphosphoglycerate
RBC
when hemoglobin is in T state what fits perfectly
2,3-bisphosphoglycerate
when t state is what kind of charge
positive charges
look at structure of 2,3-bisphosphoglycerate and think about the negative charges and how it binds to t state
pg 17
at sea level what is level of saturation of hemoglobin in lungs
100%
when at high altitude what happens to oxygen saturation in lungs
pressure of oxygen in lungs is lower
oxygen levels decreased, so there is less release of oxygen
how much oxygen is released at sea level
38%
what does body do to compensate at high altitude
body produces more BPG
what does BPG stand for
2,3-bisphosphoglycerate
if body produces more BPG what does it do to oxygen
releases more oxygen
anemia compensaes by producing more
2,3 BPG
when mutation in pyruvae kinase have high levels of
2,3 BPG
in fetus produce what hemoglobin
hemoglobin F
If remove a pos. charge in hole of hemoglobin one of the pos. charges come from his - so if you have hemoglobin without the his. the binding will decrease - don’t want that.
increases oxygen in tissues
fetal hemoglobin having less affinity for 2,3, BPG has higher affinity for
oxygen
mother vs baby oxygen
mother has lower affinity for oxygen than baby so oxygen can migrate to baby
sickle cell anemia is due to mutation in
hemoglobin
sickle cell anemia provides protection against
malaria
what is mutation in sickle cell
Glu6 → Val in the beta chain of Hb
when glutamic acid is changed to valine in hemoglobin what happen
the hemoglobin has hydrophobic bump
hemoglobin with the bump interacts with other peplomers and form a polymer and this does what
can clump capillaries, the blood cell is sickled shape
what is common treatment for sickle cell anemia
hydorxyurea
what does hydroxyurea do
prevents or makes less frequent the episodes of sickle cell
it produces more fetal hemoglobin (HbF)
HbF will replace the bad sickle cells
HbC what mutation
Glu to Lys
HbC disease
hemoglobin C disease
what hapens in HbC disease
hemoglobin crystalizes
the RBC don’t work
glu to lys is what disease
HbC disease
Why can CO kill you
it has MUCH higher affinity for Hb than O2
if you bind CO to Fe in Hb it causes what
a shift to the relaxed state - prevents release of O2 in tissues
when CO binds to Fe what does it do regarding relaxed state
prevents release of O2 to tissues
if one subunit is boudn to CO what happens to the rest of the subunits
they can no longer work
Fe has to be in what state to work
reduced
reduction of Fe3+ catalysed by what
Methaemoglobinemin reductase
what is another anme for Methaemoglobinemin reductase
NADH-cytochrome b5 reductase
congenital affects in hemoglobin making you prone to having oxidation of iron is what disease
Methaemoglobinemia
what are the two types of methmoglobin reductase
Type I and Type II
describe type I Methemoglobin reductase deficiency
soluble form of enzyme, only affects RBC, mild methamemoglibnaema
describe type II Methemoglobin reductase deficiency
soluble & microsomal form, all tissues including CNS
what is treatment for cyanide poisoning
change from normal hemoglobin to methemoglobin
why do you use methemogloibin to treat cyanide poisoning
using oxidized version of hemoglobin to trap cyanide
HbA1c is what
hemoglobin produced by glucose reaction
RBC use what to obtain energy
glucose
how can HbA1c be used to measure diabetes
there is a lot of glucose in blood to provide energy - the reaction will produce HbA1c so you can use it to measure the glucose levels in blood
what happens once there are HbA1c
have to wait for the RBC to die - once it is bound to RBC it stays bound
the carbamino effect is one method of doing what
transporting CO2 in blood
when there is high O2 in lungs, what does hb do?
binds O2 and releases CO2
most CO2 is carried how
HCO3-
draw out how most CO2 is carried in the blood as carbamino-terminal residue
pg 19
2,3 BPG is synthesized from what
intermediate of glycolysis
what does 2,3 BPG bind
deoxyhemoglobin
when 2,3 BPG binds deoxyhemoglobin what does it do
increases the energy required for conformational change
stabilises tense state
Hb-O2 + 2,3-BPG
Hb-2,3-BPG + O2
how does Cl- inhibit O2
binds neutralizing electrostatic charges
stabilizes T state
