CHEM 441PROBLEM SET 2 BIOCHEMISTRY . (A+ GRADED)

Increasing concentrations of either 2,3-bisphosphoglycerate (BPG) or protons (H+) cause a ____________ (rightward OR leftward) shift of the hemoglobin/oxygen binding curve. However, the mechanisms by which these two substances mediate this effect are distinct. Compare & contrast the way by which BPG and protons interact with hemoglobin and thereby influence its structure and function. Please be specific. Selected Answer: 1.) Rightward 2.) Only one BPG molecule can interact with hemoglobin because it binds within a specific cavity that are formed by positively charged amino acids that are between beta subunits. The negatively charged BPG will stabilize hemoglobin in the T-state when the cavity is open. However, hydrogen ions will bind to several amino acids around the HIS 146 is important. binding protons causes histidine to gain a positive charge and interact with negatively charged aspartic acid. The produced ionic bond will help in the stabilization of the T-state. Correct Answer: Increasing concentrations of either 2,3- bisphosphoglycerate (BPG) or protons (H+) cause a rightward shift of the hemoglobin/oxygen binding curve. This means that they effectively decrease the oxygen- binding affinity of hemoglobin: in the presence of BPG or H+, more oxygen is required to get the same degree of saturation. BPG is an allosteric (negative) regulator of Hb/O2 binding; BPG is a small polyanionic molecule that preferentially binds to the T-state (deoxystate) of hemoglobin. BPG fits into a positively-charged central cavity of the Hb tetramer that only exists in the deoxy conformation. Once bound, the BPG helps to stabilize the T-state of Hb. Similar to BPG, H+ does not compete with O2 for binding to the heme sites within any Hb subunit. Also similar to BPG, decreasing pH (i.e. increasing proton concentration) tends to lower the oxygen affinity of Hb. Respiring tissues generate CO2 and H+; in the tissues, Hb off-loads O2 and picks up H+ (for transport back to the lungs). Like BPG, proton-binding favors the T-state (deoxy-state) of Hb. Increased H+ concentration leads to protonation of key Hb residues involved in electrostatic interactions ("ion pairs") that stabilize the rigid deoxy conformation of HbIncreasing concentrations of either 2,3-bisphosphoglycerate (BPG) or protons (H+) cause a ____________ (rightward OR leftward) shift of the hemoglobin/oxygen binding curve. However, the mechanisms by which these two substances mediate this effect are distinct. Compare & contrast the way by which BPG and protons interact with hemoglobin and thereby influence its structure and function. Please be specific. Selected Answer: 1.) Rightward 2.) Only one BPG molecule can interact with hemoglobin because it binds within a specific cavity that are formed by positively charged amino acids that are between beta subunits. The negatively charged BPG will stabilize hemoglobin in the T-state when the cavity is open. However, hydrogen ions will bind to several amino acids around the HIS 146 is important. binding protons causes histidine to gain a positive charge and interact with negatively charged aspartic acid. The produced ionic bond will help in the stabilization of the T-state. Correct Answer: Increasing concentrations of either 2,3- bisphosphoglycerate (BPG) or protons (H+) cause a rightward shift of the hemoglobin/oxygen binding curve. This means that they effectively decrease the oxygen- binding affinity of hemoglobin: in the presence of BPG or H+, more oxygen is required to get the same degree of saturation. BPG is an allosteric (negative) regulator of Hb/O2 binding; BPG is a small polyanionic molecule that preferentially binds to the T-state (deoxystate) of hemoglobin. BPG fits into a positively-charged central cavity of the Hb tetramer that only exists in the deoxy conformation. Once bound, the BPG helps to stabilize the T-state of Hb. Similar to BPG, H+ does not compete with O2 for binding to the heme sites within any Hb subunit. Also similar to BPG, decreasing pH (i.e. increasing proton concentration) tends to lower the oxygen affinity of Hb. Respiring tissues generate CO2 and H+; in the tissues, Hb off-loads O2 and picks up H+ (for transport back to the lungs). Like BPG, proton-binding favors the T-state (deoxy-state) of Hb. Increased H+ concentration leads to protonation of key Hb residues involved in electrostatic interactions ("ion pairs") that stabilize the rigid deoxy conformation of Hb