EK B2 Ch4 Respiratory Flashcards
respiratory system 1
- Provides oxygen to circulatory system and gets rid of CO2**
- Provides O2 to circulatory system and releases CO2
- Composed of airways and lungs
air pathway
- Air enters through nasal cavity or mouth
- Nasal cavity warms and moistens air
- Nasal hairs and mucus filter and trap particles
- Mouth and nasal cavity connect to pharynx
- Larynx branches from pharynx and is covered by epiglottis
- Larynx connects to trachea (windpipe) larynx is voice box espoghagus, epoglotis suppose to flip over and cover trachea when we swallow, obviously don’t want food and water to go through these passages think upside down tree picture, branches get smaller and smaller
mucus and cilia
one trachea, two bronchi one to right or left, then more branching into bronchioles bronchi (two bronchus) and trachea lined with cilia! and mucus both important for trying to keep pathogens and dirt out of the lungs! if think about it this whole system is pretty open to atmosphere, lot of crap can get down in there; mucus supposed to trap dirt dust and pathogens cilia beat and push the mucus and hopefully some trapped stuff up so can cough it out
smoking
antagonizes cilia, also hampers bodies ability to fight off of other pathogens smoking makes ppl vulnerable to other infections
airway structure 2
- Cartilaginous rings encircle and support trachea
- Trachea splits into two bronchi
- Bronchi branch into bronchioles within lungs
- Bronchioles terminate in alveoli (air sacs)
- Millions of alveoli in each lung
mucus and cilia elevator
muscus-cilia 2
- Trachea and bronchi are lined with ciliated respiratory epithelium
- Mucus secreted by respiratory epithelium
- Mucus traps particles and bacteria
- Mucus is beat upwards by cilia to throat (like an elevator)
- Mucus swallowed, digestive system deals with material
- Smoking → antagonizes cilia activity
Lungs
• Lungs are contained in the thoracic cavity • Covered by pleural membrane*** • Lungs are moist and stick to thoracic cavity via surface tension • Lung interior is filled with alveoli = air sacs
pulmonary surfactant
- Surfactant in lungs is critical for breathing
- Surfactant acts like a detergent and reduces surface tension of lungs and alveoli
- Without surfactant, alveolar surfaces can stick and collapse
- Premature babies lack enough surfactant → respiratory distress and failure
Alveoli 2
-Alveoli very very thin sacks at end of bronchioles Alveoli walls are one cell thick! they are hugged by the capillaries, which are also one cell thick** so this really really facilitates gas exchange–> think about connecting it to what we have said about the heart, blood comes over from heart, deoxygenated, comes over to capillaries right outside hugging surface of alveoli, so easy for oxygen to diffuse through to those capillaries and Co2 to diffuse other direction from capillaries to alveoli* goes back out nice and red very oxygenated, oxygen rich blood goes through pulmonary veins back to left side of the heart** their design maximizes surface area*** for gas exchange*
Alveoli 3
• Alveoli are extensively folded, increasing surface area • Alveoli are centers of gas exchange • Alveoli are one cell thick, capillaries surrounding them also one cell thick • Lots of macrophages (immune cells, professional eating cells do phagocytosis on pathogens, even with mucus and cilia lots of pathogens get into lungs want macrophages eat pathogens) in lungs (eat inhaled pathogens); carbon dioxide diffusing and oxygen diffusing passive through one part to the other, at this point air being breathed in air oxygen rich and blood is oxygen poor, so gradient for oxygen would be from alveoli to the capillaries that is the direction of passive movement** gradient for Co2 would be blood to alveoli* gradient in the right direction for O and CO2, so walls so thin can both go down gradient to alveoli
air sacs
• Lung interior is filled with alveoli = air sacs
pulmonary surfactant 2
walls of alveoli are very thin and fragile, without surfactant they would just pinch together and close** like this little wet sack that needs to be open* so could be very easy for walls of alveoli to stick to each other* like wet tissue paper sticking to itself, but surfactant is special substance coats inner lining of alveoli that prevents walls from sticking to themselves
fetuses and importance of surfactant
• Premature babies lack enough surfactant → respiratory distress and failure
-Fetuses do not start producing surfactant to a certain point, turns out to be the line in the sand when babies can survive outside of the womb– conversations about viability
-Fetuses produce surfactant around 23 weeks of gestation, meaning it is with current technology basically impossible to keep a fetus alive outside of the womb before 23 weeks, because if no substance that keeps alveoli open, millions of tiny tiny alveoli have to be open to get oxygen can get closed no way to shove oxygen down there, huge advances in neonatal care improving outcomes for infants born at 25 weeks of gestation* NO WAY TO OXYGENATE A FETUS WHO DOESN’T HAVE SURFACTANT* great area of science advancement to transfer oxygen to early babies
mechanisms of breathing 1
- Ventilation = breathing
- Inspiration = air intake = inhalation
- Expiration = air outflow = exhalation
- Diaphragm is muscle floor of thoracic cavity
Inspiration =
• Inspiration = air intake = inhalation
ventilation=
breathing
how mammals breathe negative pressure gradient
diaphram moves down, contracts, and upper arrows in image show rib cage moving up and out- where gas laws come in handy go down, rib cages go up and out creates more volume in thoracic cavity and also in lungs themselves, which sucks air and creates a pressure gradient for air* GREATER VOLUME IN LUNGS MEANS FOR A SECOND PRESSURE DROPS so gradient for air to go down into the lungs from atmosphere= passive process, what negative pressure breathing means we create pressure within lungs a bit negative relative to the atmosphere and air moves down that pressure gradient down into the lungs
if stabbed in chest…. pressure gradient 3
stabilize ppl but leave the knife in person’s chest until get to hospital otherwise at risk for lung collapse = caused by loss of pressure gradient*** even when not breathing, air outside of lungs has to be a bit lower than atmospheric pressure, negative pressure outside of them pressure inside body right outside of alveoli is already a little bit lower than atmospheric pressure, so when diaphragm goes down and ribcage goes up and out, then pressure gets even lower/negative so air drawn down to pressure gradient **and gets lower inside of the lungs, and air comes down from atmosphere** little space around alveoli to keep lungs inflated because pneumothorax stabbed in chest and if air from outside of space rushes in theory right outside of lungs can collapse if have atmospheric pressure right outside of the lungs, the lungs will not stay inflated*
inc pressure right outside of lungs, dec volume
pressure gradient 2
slightly lower pressure inside lungs vs outside of lungs in alveoli before you take a breathe to keep lungs inflated
pressure gradient 4 when air is finally exhaled
when we exhale diaphragm relaxes so that means it moves up again and rib cage goes back to its normal position passive process pushes air back out of the lungs, air is then exhaled
breathing is involuntary
most of the time we do not think about it, it is involuntary but we can cause muscles to breathe
tidal volume
volume of normal breath without any extra exertion of energy called title volume, normal breathe in and out
total lung capacity includes mroe than that, if took deepest breathe as you could and exhaled as har dasyou could bigger volume of air out, then residual capacity which is hte part of air not exchangd with breathe, so total lung capacity is literally everything so it is greater than lung volume*
total lung capacity does not equal tidal volume, it is greater than it! probably considerably greater*
lung volume
- Tidal volume = normal volume of a resting breath
- Vital capacity = maximum volume of air that can be voluntarily inhaled or exhaled, when breathe out as hard as you can then breathe in that is called vital capacity
- Volume of air cannot be exhaled = residual capacity, will always be some residual capacity, the volume of air not expelling from lungs
- TOTAL LUNG CAPACITY = VITAL CAPACITY + RESIDUAL CAPACITY
- Some air stays in respiratory tract (trachea, bronchi, nasal cavity) = dead space
vital capacity
= maximum volume of air that can be voluntarily inhaled or exhaled, when breathe out as hard as you can then breathe in that is called vital capacity
TOTAL LUNG CAPACITY =
• TOTAL LUNG CAPACITY = VITAL CAPACITY + RESIDUAL CAPACITY everything can draw in and out if inhale and exhale our hardest, plus whatever extra volume is down deep in ur lungs we are not exchanging on every breathe
Volume of air cannot be exhaled =
• Volume of air cannot be exhaled = residual capacity, will always be some residual capacity, the volume of air not expelling from lungs
dead space
volume of air stays in upper part of respiratory track
residual capacity has to do with lungs, but not wringing out trachea, there is some normal air left and that volume is called dead space, some lingers don’t breathe out ex. if tidal volume 500 mL, and dead space is 150 mL= then fresh air you are exchanging is only 350 mL per breathe
mechanism of breathing 2
- Contraction of diaphragm → thoracic floor descends, expands volume of thoracic cavity
- Expansion of volume decreases air pressure (negative pressure/vacuum) in lungs
- Air flows in to lungs
- Relaxation of diaphragm → thoracic floor ascends, decreases volume of thoracic cavity
- Reduction of volume increases air pressure in lungs
- Air is expelled from lungs
- Breathing is involuntary, but voluntary rib (intercostal) muscles can contribute
gas exchange in alveoli, capillaries and tissues
- O2 concentration is high in alveoli
- O2 diffuses from alveoli into capillaries and RBCs
- Higher partial pressure of O2 in alveoli → higher conc of O2 into blood (Henry’s Law) b/c O2 a gas, but in this context can think about pressure being proportional to concentration, high partial pressure of oxygen in blood means a lot of oxygen in blood** so thats what pressure means in this case it just how much oxygen is there
- CO2 concentration is high in capillaries
- CO2 diffuses from capillaries into alveoli
- O2 is released in tissues, CO2 transported from tissues
CO2 gas exchange in particular
CO2 concentration is high in capillaries
CO2 diffuses from capillaries into alveoli
O2 is released in tissues, CO2 transported from tissues
cooperativity=
once hemoglobin picks up one oxygen more favorable to pick up another and another
and why curve is S shaped
hemoglobin curve
- y axis O2 saturation of hemoglobin= how much oxygen is being held by hemoglobin
- when partial pressure of oxygen around 100 mm Hg, not surpising when blood circulating right outside of alveoli in lungs, also makes sense Y coordinate is really high, hemoglobinis VERY SATURATED WITH OXYGEN** when a lot of oxygen presnt, which explains as blood is circulating by lungs hemoglobin is really really picking up oxygen, getting picked up by hemoglobin inside red blood cells nad carried by hemoglobin*
- blood circulates then around body
partial pressure of oxygen when body at rest
- not doign any exercise, partial pressure in those environments in muscles, tissues much lower than lungs which makes sense at 40 mmHg
- when look where we are on red curve, y coordinate is quite a bit lower because hemoglobin doesnt hold as much oxygen, good becasue want oxygen to deliver it to tissues not hold onto it
- so hb letting go of oxygen, means oxygen can then diffuse over to muscle cells, brain cells etc
tissues during exercise graph
light blue arrow, y coordiante is much much lower over there, becuase releasing oxygen you want Hb to LET GO of oxygen when blood is in an oxygen poor environment* because you want hemoglobin to give oxygen to cells that need it*
so around partial pressure of oxygen when blood near lungs hb very saturated with oxygen picks up oxygen adn holds it,w hen blood circulates around and red blood cells in oxygen poor environment, hb delivers it which is key to the cells that need it
the curve literally represents how much o is held by hemoglobin, any oxygen held by hemoglobin has not yet been delivered to muscles, or other cells that need it so when blood circluating by mus;ces or you are exercising you donto want hemo holding onto oxygen you want it releasing oxygen so cells can have it, so want a low o2 saturation of hemoglobin when blood is circulating by muscles
y axis “O2 saturation of hemoglobin”
saturation literally means how much oxygen Hb is carrying
don’t want it holding oxygen want it letting go of oxygen and delviering it*
Bohr graph 1
under coniditons of lower pH
normal graph blood pH around 7.4
here at pH of 7.2 which would be pH like when exercising, rightward shift* graph moving to right but in a way the more useful thing is to look at how for every X coordinate or every value of partial pressure of oxygen, solid curve, solid line below doted line
= means throughout the whole range of parital pressure of oxygen, Hb holding less oxygen so that means better at delivering oxygen
why is it adaptive: this is adaptive because makes Hb EVEN BETTER at delivering oxygen when body really needs it and is exerting itself, anything associatd wtih exercise causes Bohr shift= hot, sweaty, acidic
Hb graph summary
you actually don’t want hemoglobin to be holding onto oyxgen, good for oxygen saturation of Hb to be low when blood circulating by tissues because that means oxygen is going from Hb and blood to cells that need oxygen
CO2 transport system 1 (part A of image)
when blood near tissues, this is what happens=
Image explaination-
- CO2 crossing interstitial fluid
- CO2 continuing journey through plasma, moves all the way from tissue cell of body RBC
- CO2 enters
- some CO2 picked up by Hb
- most carbon dioxide combines with water to form carbonic acid* H2CO3, enzyme called carbonic anhydrase* not labeled in picture but important for thisr eaction
*carbonic anhdyrase catalyzes formation of carbonic acid* ;step 5 catalyzed by carbonic anhydrase
- weak acid carbonic acid dissociates into H+ and then bicarbonate**
- H+ sensed by Hb, if Hb senses acidity changes how hb carries oxygen*, where two pathways talk to eachother ; lot of CO2 lot of H+ want hb to let go of even more oxygen*, but want oxygen pathway to know what is going on with CO2 pathway
- bicarbonate released into plasma, watery part of blood, most CO2** circulates around body as bicarbonate*** main form*** in which CO2 circulates* becuase CO2 itself as CO2 is insoluble, so HCO3- bicarbonate negatively charged so happy circulating in watery - so bicarbonate released into plasma then leaves red blood cell**
chloride ion* that moves in the opposite direction from bicarbonate that is called chloride shift* so bicarbonate goes out and chloride goes in* called chloride shift, when a chloride ion moves in opposite direction from bicarbonate* and the role of chloride there is to just balance charge if negative charge coming out need negative charge going in doesnt matter if its chloride just to keep membrane potential from getting messed up by all of this
CO2 always diffuses into or out of red blood cells**
CO2 transport to lungs second part of image B
- Bicaronate goes into red blood cell, chliride goes out, so still chloride shift there
- bicarbonate merges with H+ to form carbonic acid H2CO3–> H2CO3 carbonic acid breaks down into CO2 and H20; Hb releases any Co2 it was carrying directly, Hb carries CO2 a little bit to just regulate and know how much CO2 is present in environment, more of a regulatory thing than bulk transport*
- now Co2 leaving RBC, plasma through intersitial fluid one cell thick wall of alveoli and alveolar sact to alveolar space
- CO2 is inside of the lung; then person exhales, CO2 goes out diaphragm relaxes meaning moves back up, rib cage goes back down which is mechanism that causes all gas in alveolar space especially CO2 to be exhaled out into atmosphere
fetal curve
Bohr shift righward shift
Fetal curve leftward shift relatie to adult system and basicalky that means for any partial pressure of oxygen, fetal blood will hold onto oxygen more than adult hemoglobin*** what that means when shifts to left
trade off= fetuses really great at grabbing oxygen and holding onto it from mother, not as good at releasing oxygen to their cells, so higher affinity for oxygen but don’t release it as well* but given activity level and metabolic level for fetus that is ok matches what they need to do; after a kid is born suppose to switch over to making adult not fetul hemoglobin, if that doesnt happen person running around adult doing all activities of world need more oxygen being delivered than what a fetus needs*
hemoglobin 2
Each subunit has conformational change upon binding O2
Physical interactions between four subunits yield highly cooperative binding
If one subunit is bound, other subunits are more likely to bind
Cooperativity gives sigmoidal behavior for O2 binding/dissociation
effects of pH, temperature and CO2 on hemoglobin
Protons bind to hemoglobin and promote deoxyhemoglobin conformation (bind to allosteric, regulatory sites on hb that bind protons nad Co2** and that changes affinity doing confirmational changes, those are regulatory molecules binding sites)
Hemoglobin releases O2 more readily in acidic environment
CO2 in blood forms carbonic acid, increasing blood acidity
CO2 in blood favors O2 release, shifting dissociation curve to right
CO2 also affects O2 binding by a direct mechanism
CO2 binds at a different site on hemoglobin, causing O2 release from heme
Increased temperature also promotes O2 dissociation
carbon dioxide transport 2
CO2 is transported in blood
A little CO2 gas soluble in plasma
Some CO2 bound by hemoglobin
Most CO2 converted to bicarbonate in plasma, travels in plasma as bicarbonated, IT IS ALWAYS CONVERTED TO bicarbonate in RBC*****
CO2 + H2O → H2CO3 → H+ + HCO3–
H2CO3 = carbonic acid
HCO3– = bicarbonate
CO2 diffuses into RBCs
Carbonic anhydrase enzyme accelerates carbonic acid formation
Bicarbonate diffuses out of RBCs and into blood
Cl– ions diffuse into RBCs to replace bicarbonate = chloride shift
bicarbonate buffering system in blood–>formula in body
Most CO2 converted to bicarbonate in plasma
CO2 + H2O → H2CO3 → H+ + HCO3–
H2CO3 = carbonic acid
HCO3– = bicarbonate
myoglobin
has a hyperbolic oxygen dissocatin curve**
Myoglobin can be present to hold onto oxygen in muscle cells, not used to carry oxygen like Hb just ot hold onto oxygen! it has a higher affinity to oxygen to bind to oxygen than Hb
doesnt move/circulate with oxygen!
in muscle, myoglobin will bind O2 released by hemoglobin!
Q3. Within the lungs:
a. carbonic anhydrase alters the equilbrium concentrations of H2Co3 and HCO3-
b. Co2 is picked up by hemoglobin
c. protons are released by hemoglobin
d. more bicarbonate is released from red blood cells than is picked up
c. protons are released by hemoglobin
H+ is an allosteric regulator of hemoglobin* all abotu Co2 transport, talking about O2 transport when hot sweaty and acidic hemoglobin does the boreshift, thgis si where it works where H+ is binding to hemoglobin and telling it ot let go of more oxygen*
Bicarbonate main circulating form of CO2 into plasma, then blood circulates all around to the lungs and jump over the right handside of figure, bicarbonate re-enters the blood cel and gets converted back to H2co3 carbonica cid, spins off some H…… look on image
only thing no tmentioned here is the chloride shift: everytime on left when bicarbonate goes out of the red blood cel number 8, chloride is moving in to balance the engative charge so if negative charge is moving out other negative charg is moving in, when bicarbonate going into cell near 10 chloride is simulatenously movin gout ot balance the negative charge* so negative tays the same
so on this q- right side of picture see purple Hb is releasing protons the arrow going down with an H+ that is where you can see on this diagram the question to question 3*
not d- becuase within the lungs at point 10, number 10 shows bicarbonate is mostly going INTO The red bloos cell at that point becusae it has to be converted to CO2 which will be exhaled while we are here at hte lungs**
a wrong becuase enzymes never ever alter equlibirum, they just make things go faster*** why that is wrong! carbonic anhydrase is still there and working but do not impact equilibirum concentrations***
Q. 16 Unlike hemoglobin, myoglobin has a hyperbolic oxygen dissociation curve as shown below. One conclusion that may be drawn from this graph is that:
a. at most concentrations, the affinity of myoglobin for O2 is less than that of hemoglobin
b. in the lungs, myoglobin and hemoglobin both exhibit cooperative binding of O2
c. in muscle, myoglobin will bind O2 released by hemoglobin
d. all of the above conclusions are correct
c. in muscle, myoglobin will bind O2 released by hemoglobin
Why is myoglobin unsuitable as an O2 transport protein but well suited for O2 storage?
The relationship between the concentration, or partial pressure, of O2 (Po2) and the quantity of O2 bound is expressed as an O2 saturation isotherm (Figure 6–5). The oxygen-binding curve for myoglobin is hyperbolic. Myoglobin therefore loads O2 readily at the Po2 of the lung capillary bed (100 mm Hg). However, since myoglobin releases only a small fraction of its bound O2 at the Po2 values typically encountered in active muscle (20 mm Hg) or other tissues (40 mm Hg), it represents an ineffective vehicle for delivery of O2. When strenuous exercise lowers the Po2 of muscle tissue to about 5 mm Hg, myoglobin releases O2 for mitochondrial synthesis of ATP, permitting continued muscular activity.
Both monomeric myoglobin and tetrameric hemoglobin reversibly bind oxygen and, thus, assist oxygen transport by overcoming the low solubility of oxygen in water. Myoglobin functions in the muscle to store and facilitate diffusion of oxygen in the muscle, whereas hemoglobin is responsible for the transport of oxygen throughout the body. Consistent with these roles, myoglobin has a much higher affinity for oxygen, permitting transfer of oxygen from hemoglobin in the blood to muscle myoglobin. Readily apparent in the above plot is the drastic difference in shape for myoglobin and hemoglobin.
The oxygen dissociation curve for myoglobin has a hyperbolic shape, as is expected for a simple equilibrium using independent binding sites. Its largest slope is at the lowest concentration of substrate and, as oxygen binding sites are filled, the slope steadily decreases.
Oxygen dissociation curves of hemoglobin have a sigmoidal or S - shape. This is totally inconsistent with binding at independentsites. Instead it implies that, in some way, binding of one molecule affects binding of other molecules. This sigmoidal curve starts with a very shallow slope at low ligand concentration, as though binding is restricted. The steepest portion of the curve occurs at higher ligand concentration. The theory of protein allostery provides an explanation for this complex ligand binding behavior
myogblobin vs. hemoglobin
Myoglobin releases oxygen in response to the muscle’s immediate needs.
Hemoglobin’s cooperative binding allows it to respond to changes in oxygen availability.
The oxygen dissociation curve for hemoglobin has a sigmoid shape because of the co-operative binding of oxygen to the 4 polypeptide chains. On the other hand, Myoglobin is made up of a single polypeptide with only one heme group and hence is not capable of cooperative binding.
Hemoglobin
We draw a sigmoidal curve that plateaus just below 100% saturation. Cooperative binding produces this sigmoidal shape.
– As one oxygen molecule binds, hemoglobin’s affinity for additional oxygen increases, and its percent saturation rapidly increases.
We show that hemoglobin reaches half saturation in the peripheral tissues – it responds to oxygen availability and releases it when partial pressure is low.
Myoglobin
We draw a hyperbolic curve to the left of the hemoglobin curve, a much simpler binding pattern that corresponds to myoglobin’s single heme group.
– Myoglobin has a high affinity for oxygen, and does not release it until the partial pressure is very low.
– These binding properties correspond to myoglobin’s role in oxygen storage.
– We label the early portion of the curve “Exercising muscle” and the plateau “Muscle at rest.”
Remember for dissociation curves:
– 30 torr is ~ the partial pressure of oxygen in the body’s tissues.
– 100 torr is ~ the partial pressure in the lungs.
The y-axis % oxygen saturation: it’s numbered 0 to 100.
We draw a graph and label the x-axis oxygen partial pressure (torr). Number it 0 to 120.
Hot, sweaty and acidic impact
Rightward shift indicates that the hemoglobin under investigation has a decreased affinity for oxygen whereas a leftward shift indicates that hemoglobin under investigation has an increased affinity for oxygen.
Temperature
A decrease in temperature shifts the curve to the left while an increase in temperature shifts the curve to the right. When temperature increase, the bond between oxygen and hemoglobin gets denatured and this increases the amount of oxygen and hemoglobin and decreases the concentration of oxyhemoglobin. It is usually difficult to notice the effect of temperature, but in cases of hypothermia or hyperthermia, the effects are clearly noticeable.
Organic Phosphates
2, 3-Diphospoglycerate (2,3-DPG) is the main primary organic phosphate. An increase in 2, 3-DPG shifts the curve to the right while a decrease in 2,3-DPG shifts the curve to the left. 2, 3-DPG binds to hemoglobin and rearranges it into the T state, which decreases its affinity for oxygen.
PH
An increase in PH shifts the curve the left whereas a decrease in PH shifts the curve to the right. This happens because a higher hydrogen ion concentration causes a change in amino acid residues that stabilizes deoxyhemoglobin in a state known as (the T-State), that has a lower affinity for oxygen. This rightward shift is known as Bohr Effect.
Carbon Dioxide (CO2)
An increase in CO2 shifts the curve to the right whereas a decrease in CO2 shifts the curve to the left. Hemoglobin binds with CO2 more readily than oxygen. Accumulation of CO2 results to formation of Carbamino compounds which then binds to oxygen to form carbaminohemoglobin which then stabilizes deoxyhemoglobin in the T state. Also, accumulation of CO2 causes an increase in hydrogen ion concentration and a decrease in PH and consequently shifts the curve to the right.
heme in carrying oxygen
Oxidation and reduction of the Fe and Cu atoms of cytochromes are essential to their biologic function as carriers of electrons. By contrast, oxidation of the Fe2+ of myoglobin or hemoglobin to Fe3+ destroys their biologic activity.
The pyrrole rings and methyne bridge carbons are coplanar, and the iron atom (Fe2+) resides in almost the same plane. The fifth and sixth coordination positions of Fe2+ are directly perpendicular to—and directly above and below—the plane of the heme ring.
Cyanide and carbon monoxide kill because they disrupt the physiologic function of the heme proteins cytochrome oxidase and hemoglobin, respectively. The secondary-tertiary structure of the subunits of hemoglobin resembles myoglobin.
For example, 2,3-BPG promotes the efficient release of O2 by stabilizing the quaternary structure of deoxyhemoglobin.
Isolated heme binds carbon monoxide (CO) 25,000 times more strongly than oxygen. Since CO is present in small quantities in the atmosphere and arises in cells from the catabolism of heme, why is it that CO does not completely displace O2 from heme iron? The accepted explanation is that the apoproteins of myoglobin and hemoglobin create a hindered environment. When CO binds to isolated heme, all the three atoms (Fe, C, and O) lie perpendicular to the plane of the heme. This geometry maximizes the overlap between the lone pair of electrons on the sp hybridized oxygen of the CO molecule and the Fe2+ iron.
However, in myoglobin and hemoglobin the distal histidine sterically precludes this preferred, high-affinity orientation of CO, but not that of O2. Binding at a less favored angle reduces the strength of the heme-CO bond to about 200 times that of the heme-O2 bond (Figure 6–3, right) at which level the great excess of O2 over CO normally present dominates. Nevertheless, about 1% of myoglobin typically is present combined with CO.
Heme carrying O2 vs CO
just likes orientation better so binds more*
CO binding to Hb details
In order to undestand this:
Hemoglobin exists in two major conformational states: Relaxed (R ) and Tense (T)
- R state has a higher affinity for O 2.
- In the absence of O 2, T state is more stable; when O 2 binds, R state is more stable, so hemoglobin undergoes a conformational change to the R state.
- The structural change involves readjustment of interactions between subunits.
SO NOW CO binding
Carbon monoxide (CO) binds to hemoglobin with an affinity that is more than 200 times greater than that of oxygen.
CO binds to free heme 20,000 times more tightly than does O2.
Since it binds similarly to O2 and at the same site, small quantities of CO effectively displace oxygen and stabilize the higher affinity “R” state. As a result, CO binding not only lowers the capacity of hemoglobin (by filling sites) but also shifts the allosteric equilibrium towards the R-state (relaxed state) such that the oxygen that is carried by hemoglobin is less likely to be released at the tissues, which exasperates the toxic effects of CO.
Q.20. Consider the bicarbonate buffering system in blood. Which of the following statements is correct?
a. as the concentration fo CO2 increases, blood pH will inc
b. an excess of protons in blood will favor the formation of bicarbonate
c. when carbonic acid dissociates, it forms one molecule of bicarbonate and one molcule of hydroxide
d. as the concenctration of CO2 in the blood decreases, Cl- ions exit erythryoctes and enter hte bloodstream
d. as the concenctration of CO2 in the blood decreases, Cl- ions exit erythryoctes and enter hte bloodstream
b. would push equiliboirum in other directon like gen chemistry* le chatlier principle would push equ toward carbonic acid NOT toward bicarbonate***
