Prepared by: Vishal Patel Professor: Dr. E. Thornton CHEM 504 Hemoglobin Prepared by: Vishal Patel Professor: Dr. E. Thornton CHEM 504 http://www.rcsb.org/pdb/molecules/pdb41_1.html.

Hemoglobin A protein in red blood cells that carries oxygen to peripheral tissues to maintain cells made from two similar proteins (alpha and beta) Both proteins must be present for hemoglobi to pick up and relase oxygen Before birth beta protein is not expressed. Gamma, a hemoglobin protein found only during fetal development.

Hemoglobin Overview http://video.google.com/videoplay?docid=-4144556175530726079&q=hemoglobin&total=62&start=0&num=10&so=0&type=search&plindex=0 (video)

How is Hemoglobin Made? The blueprint for hemoglobin exists in DNA. An individual has four genes that code for the alpha protein, or alpha chain. Two other genes code for the beta chain. The alpha and beta chains are made I equal amounts. The protein chains join in developing red blood cells, and remain together for the life of the red cell.

Structure of Hemoglobin Hemoglobin is composed of 4 globin molecules. 2 alpha globins 2 beta globins http://www.bloodless.it/hemoglobin.jpg

Alpha & Beta Globins http://www.uic.edu/classes/bios/bios100/lecturesf04am/hemoglobin.jpg

Hemoglobin Structure The alpha globin chain is composed of 141 amino acids & the beta globin chain is composed of 146 amino acids Both alpha and beta proteins share similar secondary and tertiary structures Each with 8 helical segments Each globin chain also contains one heme molecule. heme molecule is composed of a porphyrin ring, which contains 4 pyrrole molecules cyclically linked together, and an iron ion ligand bound in the center.

Hemoglobin Structure The heme molecule is located between helix E and helix F of the globin protein. The alpha and beta subunits of the globin chains exist in two dimers which are bonded together strongly (Keates, 2004).

Hemoglobin Structure Oxygen binds to the iron ion tightly, and if two heme molecules come together in the presence of oxygen the iron atoms will oxidize and irreversibly bind to the oxygen. This irreversible binding would not be of use in the hemoglobin molecule because oxygen needs to be released in the tissues. The globin chain prevents this irreversible binding by folding the protein around the heme molecule, creating a pocket to isolate the heme molecule from other heme molecules (Perutz, 1978). The globin molecules allow the iron atom to form loose bonds with the oxygen, and therefore, the ability to bind to oxygen and then release it into the tissues without becoming permanently oxidized in the process.

Hemoglobin Function CARBON DIOXIDE CO2 TRANSPORT IN BLOOD Mechanism one for CO2 transport in the blood: Hb ·O2 + CO2 Ö Hb ·CO2 + O2 Hb ·CO2 = carbaminohemoglobin Hb ·O2 = oxyhemoglobin

Hemoglobin Function CO2 + H2O Ö H2CO3 Ö H+ + HCO3- As CO2 passes through RBC membranes, the "carbonic anhydrase enzyme" promotes conversion of CO2 to carbonic acid (H2CO3) via the following reaction (http://faculty.etsu.edu/currie/gastrans.htm)

Hemoglobin Function The Bhor Effect CO2 + H2O  HCO3- + H+ “The ability of hemoglobin to release oxygen, is affected by pH, CO2 and by the differences in the oxygen-rich environment of the lungs and the oxygen-poor environment of the tissues. The pH in the tissues is considerably lower (more acidic) than in the lungs. Protons are generated from the reaction between carbon dioxide and water to form bicarbonate This increased acidity serves a twofold purpose. First, protons lower the affinity of hemoglobin for oxygen, allowing easier release into the tissues. As all four oxygen atoms are released, hemoglobin binds to two protons. This helps to maintain equilibrium towards the right side of the equation. This is known as the Bohr effect, and is vital in the removal of carbon dioxide as waste because CO2 is insoluble in the bloodstream.” (https://sharepoint.cisat.jmu.edu/isat/klevicca/Web/isat454/hemoglobin_essay.htm)

If you need a tutorial refer to the following web sites. http://www3.interscience.wiley.com:8100/legacy/college/boyer/0471661791/structure/HbMb/hbmb.htm

Oxygen Transport Oxygen diffuses from alveolar air into the blood because the venous blood has a lower partial pressure. The oxygen dissolves in the blood Small amount is carried as solution 0.31-ml per 100-ml The remainder of the oxygen is carried I chemical composition with the hemoglobin in red blood cells

Hemoglobin behaves as a weak acid (K=1.4X10-8; pKa=7.85) Oxhemoglobin (HHgbO2) also behaves as a weak acid (K=2.5X10-7; pKa=6.6) Because both forms of hemoglobin are weak acids, the net reaction for the interaction for oxygen with hemoglobin results in the following equilibrium. HHgb + O2  HgbO2 + H+

Hemoglobin/Oxygen Binding http://www2.austin.cc.tx.us/~emeyerth/hemoglob.htm

References http://tutor.lscf.ucsb.edu/instdev/sears/biochemistry/tw-hbn/hba-overview.htm http://www.dartmouth.edu/~rpsmith/Oxygen_Transport.html http://www.bio.davidson.edu/Courses/anphys/1999/Dickens/introduction.htm http://www.medicinenet.com/hemoglobin/article.htm http://www.chembio.uoguelph.ca/educmat/chm356/3560L2.pdf http://www.chembio.uoguelph.ca/educmat/chm356/3560L3.pdf http://www.chembio.uoguelph.ca/educmat/chm356/3560l4.pdf http://www.psc.edu/science/Ho/Ho.html#hemoglobin https://sharepoint.cisat.jmu.edu/isat/klevicca/Web/isat454/hemoglobin_essay.htm