M1 L1-2 Flashcards
protein structures and Allosteric effectors of hemoglobin and O2 delivery
what is the function of myoglobin?
where is it found?
it transports O2 & releases it over short distances, its a storage protein in muscles & tissues, has a high O2 requirement
what bonds form and maintain the tertiary structure in myoglobin?
weak interactions
what is the function of hemoglobin and where is it found?
it is a delivery protein and it brings O2 to tissues, it is found in red blood cells
list the essential features of hemoglobin structure
Tetramer 2 α & 2 β- protein subunits, each has a globular protein and a prosthetic heme group (consists of Fe2+ which oxygen binds to in centre)
what holds the hemoglobin subunits together?
weak interactions
what are the biding properties of Mb? how does O2 binding difference relate to this?
has a high affinity for oxygen and does not have a cooperative binding with oxygen like heme
describe the Bohr effect. relationship between H+ and CO2 in RBCs
heme shows a pH dependent affinity for O2; the lower the pH the lower the affinity. The reason for this is that the T state of heme is a stronger base than the R state so increased [H+] favors the low affinity T state, causing increased P50 (O2 pressure at 50%) and O2 release
Describe the molecular mechanism of heme cooperativity of O2 binding. Describe the mechanism of the cooperative T to R-state transition upon O2 binding
heme can switch between 2 states, higher O2 affinity (strong binding) and lower O2 affinity (weak binding) increasing PO2, O2 binds to a few heme switching T ⇌ R equilibrium of the tetramers towards being in the R state
explain the structure and function of hemoglobin to explain genetic disease states resulting from the alteration of key amino acids within hemoglobin.
mutations in the a1-b2 Hb tetramer contact region interfere with allosteric (T to R) mechanism. some mutations cause impaired O2 release and diminished Bohr effect as T state is less stable.
what are the biding properties of heme? how does O2 binding difference relate to this?
allosteric binding, cooperative binding
Explain how heme is better suited for long range transport, hetero-allosteric effectors
heme has a high affinity for O2 in the lungs, (high Po2 environment) which maximizes O2 binding. because some molecules affect the O2 binding by heme, these are allosteric effectors of heme binding of O2. Some of these molecules are also transported by heme
Describe the role of 2,3-bisphosphoglycerate in erythrocytes and the molecular basis of its stabilization of the T-state quaternary structure.
heme T to R state transition requires disruption of noncovalent interactions (salt bridges) between the heme monomers and a 2,3-BPG that stabilizes the T state
what are the important characteristics of the molecule BPG in terms of its interaction with heme?
it is small enough to fit into the pocket formed by the quaternity structure of deoxy heme and it carries several negative charges
where does BPG bond to heme and how many bind?
Binds in a pocket in the centre of the tetramer (on one side). One BPG per heme tetramer
Which state of heme does BPG bind to, and what is the net effect of BPG binding?
It ONLY binds to deoxy heme (T-state). This state is stabilized, making it harder for oxygen to re-bind to heme except at high O2 concentrations.
