Main Ideas - An allosteric enzyme is regulated by an effector molecule that binds to the allosteric site (not the substrate binding site)"- Enzymes that catalyze the rate-limiting step of a metabolic pathway are often allosterically regulated"- Allosteric regulation can be postive or negative, cooperative, homotropic or heterotropic"- Hemoglobin is an allosteric protein, but not an enzyme"- Binding of O2 to hemoglobin is an ex. of positive (homotropic) coopertivity"- Hemoglobin is under heterotropic regulation by H+, 2,3-BPG, and CO2""Learning Objectives 1) Understand allosterism and the concept of an allosteric binding site - Metabolic pathway: E1 catalyzed rxn is the rate-limiting step, most highly reg, largest - delta G (most irreversible), following rxns have delta G values near 0 (freely reversible)"- Feedback regulation: the end product (E) can inhibit the regulatory enzyme E1 by directly binding to it"- E doens't resemble A (substrate), it binds to the allosteric site on the enzyme"- Allosteric regulation can be postive (activating) or negative (inhibitory)"- Most allosteric prots are multi-subunit and have multiple binding sites"- Ligand binding at one site --> conformational change --> alters affinity of binding at a 2nd site"- POSITIVE coopertivity (makes it more likely next ligand will bind)"- NEGATIVE coopertivity (makes it less likely next ligand will bind)"- Homotropic modulator: regulator is a substate for its target enzyme (Ex. O with Hg)"- Heterotropic modulator: regulator is not a substrate for its target enzyme (majority)" 2) Be able to describe the structure of myoglobin and hemoglobin - Hemoglobin: need it for transport of oxygen in large, multicell animals to deliver O to deep tissues"- Globin fold w/heme group carries it out"- Each Hemoglobin carries a heme (which has iron in the middle) and each heme can bind an oxygen"- Developmental expression of globin genes"- HbF: fetal hemoglobin, higher affinity for oxygen than mom= how it steals oxygen "- alpha not on this pic because you always have that "- Myoglobin is found in muscle "cells, functions as monomer, secondary structure almost identical to a hemoglobins subuni 4) Know the allosteric regulators of hemoglobin - Hb subunits exists in 2 states: Tense "T" state (hard to bind O2) and Relaxed "R" state (faciliates O2 binding)"- First O2 binds to deoxy Hb --> conformational changes that make binding of O2 to other subunits easier"- each additional O is making it more and more likely for oxygen to bind, increasing affinity for the ligand (O)"- oxygen binding of myoglobin and hemoglobin"- myoglobin binds tighter than Hg --> facilitate O2 transfer from bloodto tissue"- more saturated w/O2 at higher partial pressures "- 2,3-BPG effect"- 23BPG formed in RBCs"- only binds T state Hb and forms salt bonds --> stabilizes T state --> decreases O2 binding affin. of Hg --> helps unloading of O2 in peripheral tissues (aka you don't want the Hg to take O from your tissues after dropping it off!)"- = a negative allosteric inhibitor (heterotropic effects) - 2,3-BPG binds less tightly to HgF and helps to transfer oxygen from maternal to fetal blood" 3) Understand the Bohr effect - As pH decreases, the affinity of pH for O2 decreases "- If pH decreases (more protons), it will DECREASE the affinity of Hg for O2 --> easier to unload O2"- If pH increases (fewer protons) it will INCREASE the affinity of Hg for
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