Chapter 5 Flashcards
why can many proteins undergo reversible interactions with other molecules
the interactions serve to regulate protein function
what is a molecule reversibly bound by the protein called
ligand
what can a ligand be
any kind of molecule including another protein another protein
what does a target + ligands create
through docking it creates a complex
where does the ligands bind to
a specific site on the protein called the binding site
how is the binding site complementary to the ligands
interms of shape, charge, hydrophobicity, hydrogen bonding potental
can a protein only have one binding site for ligands
no a given protein may have multiple binding sites for multiple ligands
i.g. ligands of hemoglobin include oxygen and 2,3 bisphosphoglycerate (2,3 BPG)
what can the binding of a ligand change
it can cause conformational change in the protein
what can the induced fit of a binding of a ligands change
it can change the properties of the protein
these chanes in protein structure often relate to changes on function
what is an example of an element that has a affinity for O2
Fe
what are the challenges of oxygen delivery and storage
every cell requires a constant supply of oxygen
what are the obstacles for oxygen delivery and storage
-for many multi-cellular organsims the solubility of oxygen is too low to meet oxygen requirements through passive diffusion
-amino acid side chains not well suited for reversible binding of oxygen
-transition state metals have a strong tendency to bind oxygen but produce damaging free radicals
what are the solutions for the challenges of oxygen delivery and storage
-specialized proteins for oxygen storage and delivery
-heme groups to safely harness irons oxygen binding properties
what is myogobin (Mb)
monomeric protein that facilitates oxygen storage in peripheral tissue
what kind of structure is myoglobin (Mb)
tertiary structure
how does myoglobin bind to O2
has a single heme group that binds to single O2 molecule
(strong affinity for O2 to make it harder to strip away)
what is hemoglobin (Hb)
a tetrameric protein found in red blood cells that transports oxygen from lungs to the periphery
what has a stronger afinity for O2 Hb or Mb
myoglobin
what can the amount of available oxygen do to an organism
it can limit its size. (availability of O2 limits size)
when is oxygen poorly soluble
in aqueous solutions
what did the emergence of larger multicellular organism depend on
the evolution of proteins that could transport and store oxygen
what forms is cellular iron bound in
forms that sequester it and/or make it less reactive
what does heme consist of
a protoporphyrin ring system bound to a singe (Fe2+) iron atom
why does heme contain Fe 2+ and not 3+
because Fe2+ binds O2 reversably Fe3+ does not
how does the ring system in a heme provide four coordinating interactions with the iron atom
the electron donating characteristic of nitrogen (found in the ring) prevents the conversion of Fe2+ to Fe3+
who uses heme
both myoglobin and hemoglobin
how is heme bound with myoglobin and hemoglibin
with discrete pockets
how many coordinating interactions does Fe 2+ seek
6
where does the six coordinating interactions for Fe 2+ come from
-4 from interactions with heme
-a 5th from interactions with imidazole group of s proximal histidine residue
-six positioning for O2 binding
what provides a stabilizing interaction for bound O2 (that is off the Fe2+)
a distal histidine provides a stabilizing interaction
what is the difference in structure of deoxyhemoglobin and oxyhemoglobin
the Fe has a O2 off it on oxyhemoglobin
how can one get CO poisoning
-CO has a simular structure to CO2
-CO exerts its deadly effects by competing with O2 for binding to heme
-CO binds heme withe 200x greater affinity than O2
how does Mb compare to Hb in terms of structure
-myoglobin with a single subunit is a tert structure
-hemoglobin, with 4 sub-units is an example of a quartinary structure
how does Mb compare to Hb in terms of oxygen binding
-with single heme group myoglobin can bind one oxygen molecs
-with four heme roups hemoglobin can bind 4 O2 molecs
what does each sub unit of hemoglobin resemble
myoglobin
how does Mb compare to Hb in terms of O2 affinity (graph)
-myoglobin has a higher affinity for oxygen than hemoglobin
-myoglobin has a hyperbolic curve of oxygen bonding
-binding of oxygen by hemoglobin displays sigmoidal behavior (indicating coopertivity of oxygen bonding)
what does hemoglobin not have to be 100% saturated
is can for example be 25% saturated because it has 4 subunits
can myoglobing be 50% saturated
no its either saturated or its not
how many torr of O2 would be required to saturate 50% of heme and myoglobin(even though it cant be)
around 3 torr for myoglobin and 30 torr for hemoglobin
(myogobins affinity for O2 is about 10x higher them hemoglobin)
what does myoglobin consist of
-a single poly peptide of 153 residues arranged in 8 alpha helicies
-a heme (iron porphyrin) prostetic group
what was the first protein structure determined
sperm whale myoglobin. determined by x-ray crystallography
why did they look for myoglobin in a sperm wale
because they would be very high in it
what is the oxygen saturation curve of myoglobin
it is hyperbolic, indicating a single O2 binding constant
what is the P50
they way to quantify the amount of O2 required to half saturate a protein
what is the P50 of myoglobin
3 torr
where is the physiolgical O2 concentration highest and lowest. and whats the torr
-the lungs is the highest (typically 100 torr)
-the periphery is the lowest (typically 20 torr)
how is the fraction of myoglobin saturated with oxygen at a given partial pressure of oxygen calculated by
0=[pO2]/([pO2]+[P50])
i.g pp of O2 in peripheral tissue is around 20 torr
0=20/(20+3)=87% saturation
what are erthrocytes
red blood cells
how many sub units does hemoglobin have
4
what does it mean that hemoglobin is a allosteric protein
-its oxygen affinity is regulated through various physiological signals
-it can adopt 2 different conformations
-can transition from T states and R states
what kind of forms do allostatic proteins have
they have T (inactive) and R (active) forms
they are in rapid equilibrium
what has a higher affinity for oxygen the T state or R state of hemoglobin
T state has a lower affinity
(deoxyhemoglobin)
R state has a higher affinity (oxyhemoglobin)
what would happen if hemoglobin only has a high or low affinity for O2
how does hemoglobin fix this
-a protein with high affinity would saturate effectively with O2 in the lungs but not release it in the tissue
-a protein with low affinity would be able to release O2 to tissue but would not have sufficient affinity to saturate in the lungs
-hemoglobin solves this by undergoing transitions from high to low affinity states
can myoglobing undergo transitions from high to low affinity states
no it only has a single ligand binding site
what state would hemoglobin be in the lungs
the R state so it can fully saturate
what state is hemoglobin when delivering O2
in the T state so it can release the O2
how many of the the hemes just go for a ride and why
50% just go for a ride around the circulatory system. they are there to be something to count on in a time of need
what are allosteric effectors (modulators)
they bind allostatic proteins at specific sites
are allosteric effectors activators or inhibitors
they and be either or
what do allosteric activators and inhibitors stabilize
-activators stabilize the R state
-inhibitors stabilize the T state
what does it mean if the interaction is homotrophic
when the normal ligans and modulator are the same the interaction is homotrophic
what does it mean if the interaction is heterotrophic
the modulator is different from the normal ligand
what is the binding and release of O2 regulated by
they are allosterically regulated
what is an example of how the binding and release of O2 in allosterically regulated
-for example O2 is a homotrophic allosteric activator of hemoglobin
-binding the first O2 by hemoglobin causes a conformational change making easier to bind subsequent O2 (positive cooperation)
-O2 binding promotes and stabilizes the R state of hemoglobin which has higher O2 affinity the the T state
where is the iron atom on a T and R state hemoglobin
-on a T state it is just out side the plane of the heme ring
-in the R state (O2 bound) the iron moves into plane of the ring
when the iron is just out side the plane vs in the plane of ring (in R vs T state) what does this effect
the minor movement within one sub unit causes structural changes that are translated to quantinary structure of the protein
at partial pressure on oxygen found in the periphery what does hemoglobin do
the hemoglobin realeases over half of its O2 load
at partial pressure on oxygen found in the lungs what does hemoglobin do
hemoglobin completely saturates with O2
what partial pressure does the p50 of hemoglobin match
the partial pressure of O2 found in periphery
where is Hb most sensitive for O2 release
at the partial pressure of O2 found in the periphery
why is it goos Hb is most sensitive for O2 release at the partial pressure of periphery
because this allows Hb to sense and respond to changes in O2 levels in regions at greatest risk for hyooxia
what is 2,3 bisphosphoglycrate
its a heterothrophic allostaric inhibitor of hemoglobin
what would happen if we had highly purified hemoglobin
it would have an extremely high affinity for oxygen
which would limit the ability of the protein to release a O2 to the periphery
what did replacing various components of blood reveal
that 2,3 biphosphoglycrate decreases hemoglobins affinity for oxygen
what charges does 2,3 BPG carry
five units of negative charge
what does the pocket formed at the interface between the subunits of DOHb contain
six + charged residues
how does a fetus get its O2
-needs to pull O2 away from the mothers blood
-fetal heme needs higher affinity for O2 then mother
-has one amino acid change for this to happen
how does the fetus have a stronger affinity for O2
-adult Hb has 6+ residues at the 2,3BPG binding site, Fetal Hb has 4+
-decreasing affinity for 2,3 BPG translates into higher O2 affinity for fetal Hb
-(lower affinity for the allosteric inhibitor bestows higher affinity form O2)
how does altitude change O2 conc
there is less O2 at higher altitudes
why is it hard to adapt to O2 conc at higher altitudes
-adaption to high alts can rapidly occur through increased production of 2,3 BPG
-increased 2,3 BPG decreases Hb’s O2 affinity to ensure sufficent O2 delivery to periphery
what does activity at extremely high altitudes require
artificial means to provide O2
why do you need to drink lots of water at high altitudes
because when you sleep you begin to pants which leads to loss of water
what does the borh effect describe
the pH dependence of hemoglobins affinity of O2
what is hemoglobins affinity for O2 at a decreased pH
it has a lower affinity
why does active tissue have a lower pH
-increased muscle activity increases production of CO2. this CO2 eventually decreases pH
-in extreme exercise muscles produce lactic acid to further decrease pH
what does the bohr effect serve to do
to coordinate increased release of O2 to active tissue
what are the two primary challenges to cellular respiration and metabolism
-delivering sufficient O2 to the the tissue
- removing CO2 (the “exhaust” of metabolism) from the pariphery
what happens with increased muscle activity
both O2 and CO2 requirements increase with increased muscle activity
what does the the enzyme carbonic anhydrase do
once CO2 is taken up into the RBC it converts it into bicarbonate and a proton
what things happen as a result of carbonic anhydrase converting CO2
-CO2 is converted into a soluble form for transport to the lungs
-the decreased pH decreases hemoglobins O2 affinity to promote O2 release to active tissue
how does CO2 form a carbaminohemoglobin
the CO2 can form a covalent carbomate linkage to the N terminus of each chain of hemoglobin chain to form it
what are the 3 important out comes of the carbaminohemoglobin reaction
-converts CO2 into a more stable form to assist in its transport to the lungs
-carbamino hemoglobin has a lower O2 affinity than hemoglobin to promote O2 release
-the released proton promotes O2 release through the bohr effect
what is anorobic metabolism
when your working out and can still have a convorsation
what is anaerobic metabolism
working out to a point of burning more O2 then body can deliver (can only be done for a short period of time)
what happens of your body goes into O2 dept
it starts to produce lactic acid
what does lactic acid do
-it enables muscles to be able to preform for awhile in absence of insufficient O2
-it causes a pH drop within the tissue
what happens when your work out a particular muscle
the partal pressure of O2 drops in that tissue the hemoglobin will automatically release more O2 to that tissue
biologically what causes sickel cell anemia
results from a single amino acid change (Glu6Val)
what biologically happens when a single amino acid change causes sickle cell anemia
-formation of fibers from the deoxy form of HbS
-fibers tend to form in the capillaries (where the O2 concentration is the lowest) which blocks blood flow to the extremities of the body
what are red blood cells like if one has sickle cell anaemia
they become very ridged
where is sickle cell anemia prone
in places with malaria like Africa and South america. it is selected for
what is a theory as to why sickle cell anemia is selected for in parts of the world
-malaria infects RBC
-infection decreses pH in RBC
-decreaseed pH causes release of O2 from Hb
-ppl with SCA, detox HbS forms fibers deforming the redblood cell
-these deformed RBC (which contain malaria) are selectively destroyed by the spleen
what is hemocyanin
another kind of O2 carrier that invertebrates (like horseshoe crab) use
how is hemocyanin distinct form hemoglobin
-hemocyanin uses copper rather than iron(blue blood instead of red)
-2 Cu atoms bind a single O2
-no heme ring group, Cu atom is coordinated through histidine residues
-hemocyanin is not localized within specialized O2 transport cells
