Hemoglobin & Oxygen Flashcards
what protein structures are considered secondary?
what interactions induce formation of secondary protein structure?
- alpha helices & beta sheets
- hydrophobic interactions
define tertiary protein structure. what is a key capacity of tertiary structures?
- 3 dimensional folding of polypeptides
- tertiary structures are able to bind other molecules
define quaternary structure
a protein structure consisting of multiple independent polypeptides
hemoglobin is
- what type of protein?
- made of what subunits/bonds?
- globular protein - aka, water soluble
- made of 4 subunits
- 2 alpha (141 AA) , 2 beta (146 AA)
- a1b1 & a2b2 bonds:
- strong bonds
- a1b2 & a2b1 bonds:
- weaker than the above bonds, but still strong: H-bonds, hydrophobic bonds, salt bridges
- a1b1 & a2b2 bonds:
- 2 alpha (141 AA) , 2 beta (146 AA)
what are the strongest protein denaturants (and at what molar concentration)?
- 9M urea - strongest
- 6M Guanidine HCl (Gdncl)
describe the affinity/effects of protein, transitional metals, and organometallic compounds to oxygen. where does Hb fit into this?
- protein = low affinity (esp in side chains)
- transitional metals = high affinity, but generate free radicals
- organometallic compounds (Fe2+/3+) = less toxic than transition metals, but free Fe3+ still reactive
hemoglobin provides a solution, as the 4 Fe+ containing heme groups are not “free” and thus not risks for reactivity.
contrast the affinity of Mb & Hb for O2. what is the reason for this & why is it important?
- myoglobin
- higher affinity
- hyperbolic curve
- requires lower O2 partial pressure to release it to environment
- hemoglobin
- lower affinity
- sigmoidal curve
- due to 4-subunits working in cooperation
- more readily releases O2 to the environment
define holoprotein & apoprotein
Holoprotein: a protein with attached prosthetic group
Apoprotein: without the prosthetic group
describe the structure of heme & the characteristics of the atoms that form it.
- heme = Fe2+ (ferrous iron) bonded to a surrounding porphyrin ring
- the porpyrin ring = carbon chain + 4 N groups & methyl, vinyl and propionic acid (- charge) side chains
there is one heme group per globin chain
Fe2+ is bonded to what stuctures in hemoglobin?
- 6 bonds total
- 4 to the porphyrin ring
- 1 to the proximal histidine - pulls Fe2+ slightly out othe plane of the ring
- 1 to O2 when hemoglobin is oxygenated
- this induces a conformation change that pulls Fe2+ BACK into the & realigns the His/F-helix
explain the T & R states of Hb & what they allow
- T and R states are responsible for the “cooperativity” and sigmoidal curve characteristic of Hb
- T vs R
- T (tense) state
- low affinity for O2
- more stable (more interactions)
- R (relaxed) state
- high afifnity for O2
- more flexible (fewer interactions)
- T (tense) state
what triggers the T–>R conformation change & what bonds are broken?
- triggered by O2 binding
- involves breaking of ion pairs between the a1-B2 interface
what are the agents that decrease the affinity of Hb for O2?
- H+ ions (low pH)
- 2,3-BPG
- CO2 binding to Hb chain
draw out the O2 saturation curve of Hb vs Hb + BPG (pO2 plotted against O2 saturation)
draw the O2 saturation curve of Hb at various pH levels (on a graph of pO2 vs % O2 saturation)
lower pH/high H+ = less O2 sound
how does the pH of blood change as it crosses capillaries and why is this the case?
- when tissues consume O2 from lungs, it is converted into CO2.
- that CO2 is converted to –> H2CO3 –> then H+ + HCO3.
- this H+ boots the O2 of incoming Hb.
- that’s why Hb in blood passing oxygen poor tissues is acidic
what is metHb reductase?
how does it work & what does it require?
- a cytochrome b5 enzyme that reducesmethemobloin (ferric form) back to normal Hb (ferrous form)
- NADH dependent
- NADH reduces cyt b5 to reduced form
- cyt b5 reduces Hb-Fe3+
