Sept 3 - Biochem 423 Robert A. Orlando, Ph.D. PROTEIN...

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Unformatted text preview: Biochem 423 Robert A. Orlando, Ph.D. PROTEIN FUNCTION AND REGULATION MYOGLOBIN & HEMOGLOBIN Q: HOW DOES THE BODY CARRY OXYGEN TO TISSUES? RED BLOOD CELLS – HEMOGLOBIN → MUSCLE – MYOGLOBIN MYOGLOBIN – SINGLE CHAIN POLYPEPTIDE 35 | P a g e Biochem 423 Robert A. Orlando, Ph.D. BINDING KINETICS OF O2: T he equilibrium constant, K e q , is equal to the association constant ( K a ) or 1 / K d , the dissociation constant. Unless otherwise given, the concentrations of L , P, and LP are expressed as mol/L, and K a h as the units of (mol/L) - 1 . 36 | P a g e Biochem 423 Robert A. Orlando, Ph.D. O2 binds with high affinity to myoglobin = high Ka and low Kd. Good for tissues, but is this good for O2 carrier in blood? 37 | P a g e Biochem 423 Robert A. Orlando, Ph.D. HEMOGLOBIN – 4 POLYPEPTIDE CHAINS….ONE MOLECULE Isn’t this better for O2 hand‐off from blood to tissues? 38 | P a g e Biochem 423 Robert A. Orlando, Ph.D. HOW DOES HEMOGLOBIN DO THIS? Slopes = rate of binding High affinity binding (myoglobin is just high affinity) Low affinity binding Sigmoidal curve indicates cooperativity (binding of the first O2 enhances binding of subsequent O2 molecules) 39 | P a g e Biochem 423 Robert A. Orlando, Ph.D. MECHANISM OF HEMOGLOBIN FUNCTION Transition from T (tense) state to R (relaxed) state through conformational changes transmitted through all four polypeptide chains. 40 | P a g e Biochem 423 Robert A. Orlando, Ph.D. REGULATION OF HEMOGLOBIN FUNCTION – HOW DOES IT GIVE UP O2 BOHR EFFECT – EFFECT OF PH ON O2 BINDING TO HEMOGLOBIN CO2 FROM METABOLISM IN PERIPHERY CO2 + H2O ↔ H+ + HCO3‐ LOWER PH PROMOTES TRANSITION TO THE “T” STATE ↑ H+ ‐‐‐ ↓ PH 41 | P a g e Biochem 423 Robert A. Orlando, Ph.D. ALTITUDE EFFECTS O2 BINDING TO HEMOGLOBIN ALLOSTERIC MODULATION OF HEMOGLOBIN THROUGH BINDING OF 2,3‐BISPHOSPHOGLYCERATE – FROM GLYCOLYSIS INTERMEDIATE 1,3‐ BISPHOSPHOGLYCERATE MADE IN RED BLOOD CELLS ↓ affi nity of O2 for hemoglobin Greater release of O2 at high altitudes BPG concentration at sea level BPG concentration at high altitudes 42 | P a g e ...
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