Biochem Seminar on Hemoglobin and it's derivatives and hemoglobinopathies.pptx

Biochemistry seminar

1. HEMOGLOBIN IT’S DERIVATIVES & HEMOGLOBINOPATHIES AHSAN KHAN 515/20

2. Hemoglobin (Hb) is the red blood pigment, exclusively found in Erythrocytes. Normal Concentration of Hb in blood - MALES – 14-16 g/dL
FEMALES – 13-15 g/dl It performs two important biological functions – 1. Delivery of O2 from Lungs to tissues. 2. Transport of CO2 and protons from tissues to lungs for excretion

3. Structure of Hemoglobin Hemoglobin is a conjugated protein,containing globin- the apoprotein part and the heme non protein part (prosthetic group) Hemoglobin is a tetrameric allosteric protein. Hemoglobin comprises four subunits, each having one polypeptide chain and one heme group
Hemoglobin A is the major hemoglobin in adults,is comprised of four polypeptide chains 2 α and 2 β chains held together by noncovalent interactions

4. α-chain - 141 AA
β- chain – 146 AA
Red colour of Hb is due to Haem.
Haem contains protoporphyrin IX, with iron at its center. Protoporphyrin IX consists of four pyrole rings to which 4 Methyl, 2 propionyl and 2 vinyl groups are attached.

5. BOHR EFFECT Binding of oxygen to Hemoglobin decrease with increasing H+ concentration (lower pH), increased pCO2. It is due to change in the binding affinity of oxygen to Hemoglobin. It causes right shift in the oxygen dissociation curve Effect of 2,3 BPG on O2 affinity of Hb It regulates the binding of O2 to Hb.It specifically binds to DeoxyHb and decreases the affinity to Hb. The reduced affinity of O2 to Hb facilitates the release of O2 at partial pressure found in the tissues. It shifts Oxygen dissociation curve to Right.

6. CLINICAL SIGNIFICANCE OF 2,3 BPG In Hypoxia - The concentration of 2,3 BPG in erythrocytes is elevated in chronic hypoxia. In Anemia - level is increased in severe Anemia in order to cope up with oxygen demands of body. In Blood Transfusion – Storage of blood in acid citrate dextrose medium results in decreased concentration of 2,3 BPG. Addition of inosine to the stored blood prevents decrease of 2,3 BPG..

7. . HEMOGLOBIN DERIVATIVES Heme combines with dfferent ligands and forms Hemoglobin derivatives Normal blood contains OxyHb & DeoxyHb , besides these Methemoglobin (metHb) and carboxyhemoglobin are other derivatives. Carboxyhemoglobin (COHb) It is a toxic compound that can bind with Hb as O2 binds. It has about 200 times more affinity than O2 for binding with Hb. Clinical Manifestations of Co toxicity are observed when it’s concentration exceeds 20% Symptoms- Headache,Nausea, Vomiting and irratability. Administration of O2 will help to reverse CO toxicity.

8. Methemoglobin It contains Fe 3+ instead of Fe 2+ in heme group. Oxidation of Hemoglobin to Methemoglobin (metHb) may be caused by H202, free radicals and drugs. It is unable to bind to O2
It is corrected by Methemoglobin reductase present in erythrocytes.

9. HEMOGLOBINOPATHIES It is a term used to describe disorders caused by synthesis of abnormal Hemoglobin Molecule or production of insufficient quantities or rarely both. Sickle Cell anemia (HbS) & Hemoglobin C disease (HbC) are examples of abnormal Hemoglobins. Thalassemias caused by decreased synthesis of normal Hemoglobin.

10. Abnormal Hb Gene Type Mutation Clinical Manifestations Sickl cell Anemia (HbS) HbSS Glu β6 – Val
6 th Position Chronic hemolytic anemia Acute organ syndromes
Pain crises Heterozygous Hbs HbAS Same as HbSS No apparent illness Hemoglobin C disease HbC Glu β6 – lys 6 th Position Mild Hemolytic anemia Hemoglobin D HbD Glu β121 – Glutamine 121 st Position No Clinical manifestations Hemoglobin E HbE Glu β26- lys 26 th Position No Clinical manifestations ABNORMAL HEMOGLOBINS

11. THALASSEMIAS Type of Thalassemia No of Missing Genes Clinical Symptoms α-thalassemias Normal Nil Nil Silent Carrier 1 No symptoms α-thalassemia trait (heterozygous) 2 Minor anemia Hemoglobin H disease 3 Mild to moderate anemia
may lead normal life. Hydrops fetalis 4 Fetal death usually occurs at birth. β-Thalassemias β-thalassemia minor 1 No symptoms β-thalassemia major 2 Severely anemic & die within 1-2 years.