Lecture 5: Hemoglobin (Structure, Typing, Synthesis, and Function) PDF

06 FEBRUARY 2023 LECTURE 5 Hemoglobin ( structure, typing, synthesis and function) HEMOGLOBIN ( HEMATOLOGY ) 1 Introduction • Haemoglobin is a highly specialized intracellular erythrocyte protein. • It is responsible for transporting oxygen from the lungs to tissue and facilitating carbon diox...

06 FEBRUARY 2023 LECTURE 5 Hemoglobin ( structure, typing, synthesis and function) HEMOGLOBIN ( HEMATOLOGY ) 1 Introduction • Haemoglobin is a highly specialized intracellular erythrocyte protein. • It is responsible for transporting oxygen from the lungs to tissue and facilitating carbon dioxide transport from the tissue to the lungs. • Each gram of haemoglobin can carry 1.34 ml of oxygen. • Hemoglobin occupies approximately 33% of the volume of the erythrocyte and accounts for 90% of the cell dry weight. HEMOGLOBIN ( HEMATOLOGY ) 2 06 FEBRUARY 2023 LECTURE 5 Introduction • Each cell contains between 28-34 pg of haemoglobin (MCH). • The erythrocyte membrane and its metabolic pathways are responsible for protecting and maintaining the haemoglobin molecule in its functional state. • Hemoglobin concentration in the body is the result of a balance between the production and destruction of erythrocytes. HEMOGLOBIN ( HEMATOLOGY ) 3 Hemoglobin structure: • Haemoglobin is a large tetrameric molecule, composed of four globular protein subunits. • Each of the four subunits contains a heme group and a globin chain. • Heme is an iron-chelated porphyrin ring. • The porphyrin ring is composed of a tetrapyrrole ring with a ferrous iron located in the center of the ring. • Each heme subunit can carry one molecule of oxygen bound to the central ferrous iron, thus each haemoglobin can carry four molecules of oxygen. HEMOGLOBIN ( HEMATOLOGY ) 4 06 FEBRUARY 2023 LECTURE 5 The porphyrin ring HEMOGLOBIN ( HEMATOLOGY ) 5 Hemoglobin structure: • The composition of the globin chains is responsible for the different functional and physical properties of haemoglobin. • Two types of globin chains: • 1-alpha-like (alpha ά , zeta ∂ ). • 2-non-alpha-like (epsilon €, beta ß, delta, and gamma). • -The tetrameric haemoglobin molecule consists of two pairs of unlike chains; two identical alpha like and two identical non-alpha-like to form the various types of haemoglobin. HEMOGLOBIN ( HEMATOLOGY ) 6 06 FEBRUARY 2023 LECTURE 5 Alpha & beta chains: HEMOGLOBIN ( HEMATOLOGY ) 7 Structure • 4 polypeptide Subunits • Heme group • Porphyrin ring • Iron in Ferrous , Fe ⁺⁺ form • Globin chain • 2 Alpha Chains • 2 Beta chains Hb= 4 heme + 4 globin HEMOGLOBIN ( HEMATOLOGY ) 8 06 FEBRUARY 2023 LECTURE 5 Types of Hemoglobin: • The type of haemoglobin is determined by the composition of its globin chains. Individual globin chains are expressed at different levels in the developing erythroblast of the human embryo, fetus, and adults. • Some haemoglobins (Gower l, Gower ll , Portland) occur only in the embryonic stage. • HbF is the predominant haemoglobin in the fetus and newborn. • HbA is the predominant haemoglobin after 1 year of age. HEMOGLOBIN ( HEMATOLOGY ) 9 Embryonic Hemoglobin: Embryonic Hemoglobin: • When erythropoiesis occurs inside the mother's uterus (during pregnancy), the embryonic haemoglobin Gower I, Gower ll and Portland are produced. • Although it may be found in early hematopoiesis in the yolk sac and liver, primitive haemoglobin is normally not found beyond the third month of pregnancy. HEMOGLOBIN ( HEMATOLOGY ) 10 06 FEBRUARY 2023 LECTURE 5 2- Fetal Hemoglobin • 2-Fetal Hemoglobin • HbF(ά2 γ2 ): • is the predominance of HbF infant haemoglobin during the liver and bone marrow erythropoiesis in the fetus. • HbF composes 90-95% of the haemoglobin in the foetus until 34-36 weeks of gestation. • At birth, the infants have 50-85% of HbF. HEMOGLOBIN ( HEMATOLOGY ) 11 3-Adult Hemoglobins: • HbA (ά2 ß2 ) is the major haemoglobin in adults. • It is formed during erythropoiesis in the bone marrow. • After birth, the percentage of HbA continues to increase until the normal adult level (> 95%) is reached by the end of the first year. • HbF production constitutes less than 2% of adult haemoglobin.-HbA2 constitutes 1.3-3.7% of adult haemoglobin. HEMOGLOBIN ( HEMATOLOGY ) 12 06 FEBRUARY 2023 LECTURE 5 4-Glycosylated Hemoglobin:(HbA1c) • It is produced throughout the erythrocyte life cycle. Its synthesis depends on the concentration of blood glucose. • Older erythrocytes contain more HbA1c than younger erythrocytes as they are exposed to plasma glucose for a longer period of time. • measurement of HbA1c is used as an indicator of blood glucose level in diabetic patients because it is proportional to the average blood glucose level over the previous two to three months. • Average levels of HbA1c are 7.5% in diabetics and 3.5% in normal individuals. HEMOGLOBIN ( HEMATOLOGY ) 13 Types of hemoglobin: HEMOGLOBIN ( HEMATOLOGY ) 14 06 FEBRUARY 2023 LECTURE 5 Synthesis of Hemoglobin: • Hemoglobin synthesis begins as early as the pronormolast stage. • In the polychromatic stage, most haemoglobin is synthesised. • The majority of haemoglobin production (65%) occurs before the nucleus is ejected. • The reticulocyte is capable of producing the remaining 35%. (residual RNA and mitochondria)The adult erythrocyte does not have a nucleus or mitochondria, so it can't make new proteins. HEMOGLOBIN ( HEMATOLOGY ) 15 Abnormal hemoglobins 1. Carboxyhemoglobin, Hb + CO • Oxygen molecules bound to heme are replaced by carbon monoxide. • Haemoglobin's affinity for CO is more than 200 times greater than its affinity for oxygen. • seen in heavy smokers and as a result of environmental pollution. HEMOGLOBIN ( HEMATOLOGY ) 16 06 FEBRUARY 2023 LECTURE 5 Abnormal hemoglobins 2. Methemoglobin • Iron in the haemoglobin molecule is in the ferric (Fe3) state instead of the ferrous (Fe2) state. incapable of combining with oxygen. • can occur as a result of strong oxidative drugs or of an enzyme deficiency. 3. Sulfhemoglobin • Hemoglobin molecules contain sulfur. • caused by certain sulfur-containing drugs or chronic constipation. • can not revert to oxyhemoglobin and may cause death. HEMOGLOBIN ( HEMATOLOGY ) 17 Function of hemoglobin: 1. The function of haemoglobin is to transport and exchange respiratory gases. 2. Oxygen affinity: the ease with which haemoglobin binds and releases oxygen. 3. Increased oxygen affinity means the haemoglobin does not give up its oxygen. 4. Decreased oxygen affinity means the haemoglobin releases its oxygen more readily. HEMOGLOBIN ( HEMATOLOGY ) 18