Test 2 Lecture 32-33 Flashcards
___ is the O2 carrier protein of the blood.
hemoglobin
___ is an O2 storage protein found in muscle
myoglobin
Hemoglobin has a _______ affinity for O2 in the lungs, which promotes O2 uptake and has a ____ affinity for O2 in the tissues, which promotes the release of O2.
high
lower
“protein intelligence”
Hemoglobin assists in the transport of CO2 from ___ to the ___
tissues
lung
High concentrations of ___ provide an O2 reserve in the muscles of diving birds and mammals.
myoglobin
store O2 in muscles, don’t need to breathe when diving
Myoglobin is composed of ___ helixes
aplha
The heme of myoglobin is bound ___
tightly but not covalently, can come off under extreme conditions
Heme is attached to myoglobin by ___ and ___
proximal histidine
distal histidine
The proximal histidine of myoglobin attaches to the ___
the distal histidine ___
iron of the heme
hovers above where O2 will bind, Water sits in that places when waiting for O2
iron in hemoglobin is in the ___ state
+2
when O2 is not bound to iron of hemoglobin the iron is ___
when O2 is bound to the iron of hemoglobin the iron is ___
big and pulled down by the proximal histidine
now in +3 state, gets smaller and is pulled in line with the heme
when O2 binds to iron of heme, Iron changes from ___ to ___ and the O2 forms a ___
+2
+3
superoxide ion
Distal histidine is H-bonded to bound oxygen with the H-bonding to the ____form being tighter.
superoxide
distal histidine binds better when Iron 3+
Distal histidine binding to the superoxide form inhibits the release of superoxide ions and the _____ of the iron
oxidation
Oxidized hemoglobin with Fe3+ is called ____ and does not bind O2.
methemoglobin
___ uses NADH to reduce methemoglobin and reform hemoglobin.
Methemoglobin reductase
high levels of methemoglobin leads to comma, seizures and death
In cats and dogs an intermediate of acetaminophen(tylenol) metabolism leads to formation of _________. Cats are very sensitive to this effect. Acetaminophen can also cause liver damage.
methemoglobin
Leads to the formation of methemoglobin in dogs, cats, and other animals. Clinically significant levels of methemoglobin have occurred.
Benzocaine
Seen in ruminants eating nitrate-accumulating plants, especially plants treated with nitrogen containing fertilizers. Nitrate is reduced to ______ by ruminal microbes
nitrite (cause the formation of methemoglobin)
why is methemoglobin bad
Iron in +3 state, can not bind with O2, Oxygen can not be carried to tissues
“internal suffocation”
Onion toxicity and Heinz bodies
Has been seen in cattle, sheep, horses, dogs and cats.
Onion and other plants contain chemicals that can oxidize cysteine residues in hemoglobin to disulfides, ultimately leading to denaturation and aggregation of hemoglobin. Aggregates of denatured hemoglobin in the red blood cells are called heinz bodies. Half-life of affected red blood cells is reduced. Cats are very sensitive to formation of Heinz bodies.
Aggregates of denatured hemoglobin in the red blood cells are called _________
heinz bodies
Half-life of affected red blood (Heinz bodies) cells is ____. ____ are very sensitive to formation of Heinz bodies.
reduced
Cats
This enzyme reduces methemoglobin back to hemoglobin
Methemoglobin reductase
a.k.a. cytochrome b5 reductase
Methemoglobin reductase deficiency symptoms
lethargic and exercise intolerant, but typically live normal length lives.
explain how distal histidine reduces the affinity of carbon monoxide for Iron
Carbon monoxide likes to bind perpendicular to heme
distal histidine forces it to bend= unhappy CO
O2 likes to be bent, will happily sit there
Distal histidine forces Carbon monoxide to bind in a ________ conformation. This ______ the affinity of CO for hemoglobin/myoglobin, without decreasing the affinity of hemoglobin/myoglobin for _____, which naturally binds in a bent conformation.
bent
lowers
oxygen
Hemoglobin/myoglobin still bind to carbon monoxide ____ times more tightly than oxygen, which means that CO can block the binding of O2 to hemoglobin and interfere with O2 transport.
120 to 500
treatment for CO
long term oxygen therapy
hyperbolic chamber
What other heme-containing protein complex is a target in CO poisoning?
cytochrome c oxidase
final part of the electron transport chain
what is this showing
myoglobin
if Hemoglobin has 3 O2 it is more likely to ___ an oxygen, then a hemoglobin with 1 O2, which will ___an oxygen
get/take
give away
Hemoglobin in ___ state like to take O2 want to have 4
Hemoglobin in ___state, like to give away O2 want to have 0 oxygen
R
T
explain
Myoglobin: binds very fast and completely at low O2
Hemoglobin takes time: at first has low affinity for O2, will bind slow (T state)
but as it gets more O2, affinity for O2 will increase, will bind faster (R state), will reach full saturation in the lungs around 100 torr
when at rest: 21% of oxygen available in hemoglobin has been given away (normal steady state activity
When exercising: 66% of oxygen has been used. This is on steep part of curve, want to have more O2 delivered when needed, can drop to very low amounts of O2
bohr effect
At lower pH, there is a higher concentration of protons, there protons will bind to R state Hemoglobin(full Heme) and turn it into T state Hemoglobin and 4O2
When pH is below pKa, ___ form is favored,
When pH is above pKa, ___ form is favored.
protonated
unprotonated
At physiological pH, ~ pH 7.4, an unperturbed histidine will be mostly _______
unprotinated
pH 7.4 is higher then pKa 6.5 therefore histidine will live in unprotinated form
In the T-state, histidine 146 is in close proximity to aspartate 94. This greatly ________ the protonation of this histidine residue.
increases
Lower blood pH will __ the protonation of histidine 146 and other groups that stabilize the T-state and increase the release of oxygen from hemoglobin.
increase
explain
at lower pH: blue curve: Bohr effect
lower pH will trigger T state hemoglobin, Hemoglobin will want to give away its O2
therefore at 20 torr in exercising tissues, hemoglobin will give away 77% of O2 instead of 66% at normal pH
lower pH= more acid= more need for O2
The binding of CO 2 to hemoglobin stabilizes the __
T state
Carbamate is negative charge, will stabilize T state (give away O2, graph moves to the right)
red: normal hemoglobin (give away 66% of O2
blue: low pH and no CO2 (give away 77% O2)
purple: lower pH and CO2 (give away 88% O2)
increase CO2= more acid= decreased pH
right = more T state= more O2 given away
In the tissues, hemoglobin in the T-state increases the CO2 carrying capacity of the blood by directly binding CO2, and by binding protons, which increases the amount of bicarbonate in the blood by ____ blood pH.
increasing
hemoglobin acts as buffer
In the lungs, the high concentration of O2 drives hemoglobin to the R state. These effects roughly _______ the efficiency of CO2 transport from tissues to lungs
double
2,3 BPG only binds hemoglobin in the ______ This shifts the hemoglobin O 2 binding curve to the ___
T state
right
why can’t BPG bind to R state
no room in the R state
red: fetal blood, has higher affinity for O2, shifts to the R state
low BPG, wants to hold O2 more
