Hemoglobin structure and functionDr. Niveen M. Daoud Ass. Prof. clinical pathology
Outcomes Enlist the heme containing proteins in human body Enumerate the functions of proximal & distal histidine
residues of globin chain Describe the quaternary structure of hemoglobin Differentiate b/w the tense T & relaxed R forms of hemoglobin Name the compounds which can bind to hemoglobin State the functions of hemoglobin in blood Enlist the composition of HbA, HbA2, Hb Gower 1 & HbF Discuss the formation & clinical importance of glycosylated hemoglobin HbA1c Describe the structural deformities of hemoglobin molecule in Hb S, Hb C & Hb SC diseases
Proteins that contain an iron-porphyrin, or heme, prosthetic
heme containing proteins in human body
group resembling that of hemoglobin. Hemoglobin Myoglobin Both are examples of hemeprotein that are essential in the storing and transports of oxygen in mammals. Hemoglobin is a quaternary protein that occurs in the red blood cell, whereas, myoglobin is a tertiary protein found the muscle cells of mammals. Although they might differ in location and size, their function are similar. Being hemeproteins, they both contain a prosthetic group (tightly-bound cofactors ). NP nitrophorin Cytochromes Catalase peroxidase
What are the compounds can bind to Hb Carbon monoxide (CO)
Carbon dioxides (CO2) Oxygene (O2) Nitric oxide (NO) Hydrogen sulfate (H2S) Fe+3 2,3-BPG
Hemoglobin Hemoglobin (Hb) is the protein molecule
responsible for transporting respiratory gases. The normal hemoglobin value for adult males is 14-18 grams per deciliter of whole blood.
Quaternary structure of Hemoglobin In adult humans, the most common
hemoglobin type is a tetramer (which contains 4 subunit proteins) called hemoglobin A, consisting of two and two subunits they made of 141 and 146 amino acid respectively. This is denoted as 22. The subunits are structurally similar and about the same size..
Hemoglobin has a complex quaternary
structure The four polypeptide chains are bound to each other by salt bridges, hydrogen bonds, and have hydrophobic effect. Each of the 4 globulin protein subunits contains a single nitrogenous pigmented molecule of heme. Each heme molecule contains a single iron ion which associates with oxygen to form oxyhemoglobin (a bright red pigment). Oxygen easily dissociates from the iron ion to become deoxyhemoglobin (a darker
Structure of hemoglobin
Hb tetramer is two identical dimers
Hemoglobin and chain of Hb consist of
seven and eight helical regions ( from A through H). An invariant histidine in all hemoglobins, called F8 or the proximal histidine, binds heme. . F8 refers to the eighth residue of F helix
Structure of monomer of Hb
the functions of proximal & distal histidine residues of globin chain His-F8 of the hemoglobin known as the
proximal histadine is covalently bonded to the 5th coordination position of the iron. And as an Oxygen binds to the 6th coordination position of the iron, a distal histidine (a histidine that doesn't bond directly with the Iron), HisE7 of the hemoglobin binds to the oxygen that is now covalently bonded to the iron. The same occurs for the myoglobin.
T and R status of Hb The structure of Hb differs in the oxygenated and
deoxygenated states. The quaternary structure of deoxy. Called T or taut form which has low O2 affinity. Oxygenated Hb called R or relaxed form which has high O2 affinity. Hemoglobin exists in two forms, a taut form (T) and a relaxed form (R). Various factors such as low pH, high CO2 and high 2,3 BPG 2,3,bisphosphoglycerate at the level of the tissues favor the taut form, which has low oxygen affinity and releases oxygen in the tissues as well as contains
Oxy versus deoxy hemoglobin
T and R states of Hb(conti) Differences in quaternary structure of
the R and T states are produced by the movement of F8 histidine as oxygen binds or dissociates from heme. The F8 histidine alters the position of the F and E helics and leads to altered contacts between the subunits.
Hb Tense & Relaxed States
Difference between oxy and deoxy Hb Oxyhemoglobin
Oxyhemoglobin is formed during physiological
respiration when oxygen binds to the heme component of the protein hemoglobin in red blood cells. This process occurs in the pulmonary capillaries adjacent to the alveoli of the lungs. The oxygen then travels through the blood stream to be dropped off at cells where it is utilized in glycolysis and in the production of ATP by the process of oxidative phosphorylation. It does not, however, help to counteract a decrease in blood pH. Ventilation, or breathing, may reverse this condition by removal of carbon dioxide, thus causing a shift up in pH.
Deoxygenated hemoglobin Deoxygenated hemoglobin is the form of
hemoglobin without the bound oxygen. The absorption spectra of oxyhemoglobin and deoxyhemoglobin differ. The oxyhemoglobin has significantly lower absorption of the 660 nm wavelength than deoxyhemoglobin, while at 940 nm its absorption is slightly higher. This difference is used for measurement of the amount of oxygen in patient's blood by an instrument called pulse oximeter. This difference also accounts for the presentation of cyanosis, the blue to purplish color that tissues develop during hypoxia
Methemoglobinemia Normally, methemoglobin levels are
