Lecture 1 - Protein Structure/Function (Hemoglobin Molecule) Flashcards

Question

Describe the structure of Heme

Answer 1

* There is a central core of Fe within a porphyrin ring | * Plants have a central Mg instead of this

Answer 2

T ("tense") state = deoxyHb, decreased O2 affinity * assumes a donut shape with 2,3-BPG in the center * Has 0.4 angstrom puckering of central Fe out of porphyrin ring R ("relaxed") state = oxyHb, increased O2 affinity *O2 binding Fe causes electronic rearrangement and allows heme to smooth out + interacts closer with Histidine F8, pulling on the alpha helix

Answer 3

1) Cooperative binding - 1st O2 is difficult to load but O2 affinity increases every time another binds 2) Allosteric effectors - 1st O2 binding causes conformational changes in other subunits

Answer 4

* Negative heterotropic effector of O2 binding, favoring T state * Required for cooperative O2 binding and is responsible for Hb-O binding curve * W/o it, this curve assumes a shape similar to MMb * Glycolysis byproduct * At sea level = 5 mM * [BPG] increase --> downward O dissociation curve * [BPG] decrease --> upward shift towards Mb curve

Answer 5

* Fetal Hb = 2alpha, 2gamma --> gamma chain is similar to adult Beta chain but lacks a 2,3-BPG binding residue, therefore favoring movement of O2 from maternal RBC --> fetal RBC - doesn't stabilize T state and doesn't bind BPG * Pregnant women have increased BPG --> increase O2 offloaded to fetus

Answer 6

1) Initially at regular 5 mM of BPG, the lungs pick up less O2 due to less available, but try to deliver the same amount to the tissues (30% efficiency) 2) Cells increase [2,3-BPG] to ~ 8 mM 3) Picks up less O2 in lungs due to T state favored but able to unload more O2 to the tissues (37% efficiency vs normal 38%)

Answer 7

P50 = 26 torr

Answer 8

* stabilizes T state 1) increased [2,3-BPG] 2) decreased pH - protonation of globin residues --> release of O2 from Hb (Bohr Effect) 3) increased CO2 - modifies globin N-terminal amino groups --> carbamino-terminal residue so it can be transported 4) increased temperature - increased respiration and therefore increased CO2 production * All cause right O dissociation curve shift --> decrease O2 affinity - left shift caused by the opposite

Answer 9

* Negative heterotropic effector of O2 binding - right O dissociation curve shift * H+ released upon CO2 hydration (respiration) in tissues and then this is used to protonate globin residues of Hb --> readily release O2 * decreased pH --> release of O2 * If BetaHistidine HC3 is protonated --> forms salt bridge with BetaAspartate FG1 - stabilize conformation --> betaHistidine HC3 C-terminus forms bonds with alphaLys C5 --> stabilization of deoxyHb conformation

Answer 10

* CO binds tightly to Hb and outcompetes O2 to bind to Hb * Binding 1 CO forces Hb into tightly bound conformation, not allowing O2 to be released * decreased O2 binding capacity (downward shift) and left shift - O2 remains bound even at pO2 found in tissues * No cure, can only put patient on 100% O2

Lecture 1 - Protein Structure/Function (Hemoglobin Molecule) Flashcards

Protein Structure/Function (Hemoglobin Molecule) (34 cards)