Biochemistry Sixth Edition Berg • Tymoczko • Stryer Chapter 7: Hemoglobin: Portrait of a Protein in Action Copyright © 2007 by W. H. Freeman and Company

Erythrocytes (Red cells)

Hemoglobin and Myoglobin These are conjugated proteins. A simple protein has only a polypeptide chain. A conjugated protein has a non-protein part in addition to a polypeptide component. Both myoglobin and hemoglobin contain heme. Myoglobin - 17000 daltons (monomeric) 153 amino acids Hemoglobin - 64500 daltons ( tetrameric) a-chain has 141 amino acids b-chain has 146 amino acids

Hemoglobin O2 carrying capability Erythrocytes/ml blood: 5 billion ( 5 x 109 ) Hemoglobin/red cell: 280 million ( 2.8 x 108 ) O2 molecules/hemoglobin: 4 O2 ml blood: (5 x 109)(2.8 x 108)(4) = (5.6 x 1018) or (5.6 x 1020) molecules of O2/100 ml blood

Myoglobin, monomeric

Aromatic Heme

Iron in Hemoglobin binding O2

Hemoglobin, a2b2 tetramer

O2 binding: Hemoglobin & Myoglobin P50 = 2 torr P50 = 26 torr

O2 transport capability, a comparison

Resting state vs exercise

O2 Binding Changes 4o Structure

Decreasing O2 affinity 2,3-bisphospho-glycerate (2,3-BPG) Lowers the affinity of oxygen for Hemoglobin

2,3-bisphosphoglycerate (2,3-BPG) The binding pocket for BPG contains 4 His and 2 Lys

Binding of bisphosphoglycerate

Oxygen Affinity of Fetal Red Blood Cells Fetal red blood cells have a higher oxygen affinity than that of maternal red blood cells because fetal hemoglobin does not bind 2,3-BPG as well as maternal hemoglobin does

The Bohr Effect Bohr Effect: Lowering the pH decreases the affinity of oxygen for Hb

Loss of O2 from Hemoglobin Carbamate: CO2 combines with NH2 at the N-terminus of globins

Carbamate formation Covalent binding at the N-terminus of each subunit

Sickle Cell due to Glu 6  Val 6