Download as PPTX, PDF, TXT or read online from Scribd
Download as pptx, pdf, or txt
You are on page 1/ 19
Hemoglobin
Dr. Sharad Mankar
Assistant Professor Introduction
• The cytoplasm of erythrocytes (RBCs) contains an
oxygen binding protein called hemoglobin.
• Erythrocyte precursors synthesize Hb; while the mature
erythrocytes lose the property of synthesizing Hb. Normal Values • Adult males 15.5 g/dL (range 14–18 g/dL) • Adult females 14 g/dL (range 12–15.5 g/dL) • In fetus, just before birth, the Hb concentration of blood from the umbilical cord ranges from 16.5 to 18.5 g/dL. • After birth, it increases rapidly, may reach up to 23 g/dL. • After two days of birth, the Hb levels start falling & stabilize at the end of 3 months to 10.5 g/dL. • The concentration then rises gradually to reach 12 g/dL at 1 year of age Structure of Hb • Hb is a globular molecule having a molecular weight of 68,000.
• It consists of the protein globin combined with iron
containing pigment called haem. Structure of globin • The protein globin, present in the Hb, is made of four polypeptide chains.
• Hemoglobin A (HbA) consists of the following four
polypeptide chains:
1. Two α chains, each containing 141 amino acid residues
2. Two β chains, each containing 146 amino acid residues
• The normal adult hemoglobin A is written as HbA (α2β2).
Structure of haem • The haem is an iron–porphyrin complex called iron– protoporphyrin IX • It consists of a porphyrin nucleus and the iron. Porphyrin nucleus • The porphyrin nucleus consists of four pyrrole rings numbered I, II, III and IV • The pyrrole rings are joined together by four methine bridges (=CH−) • The carbon atoms of methine bridges are labelled α, β, γ and δ Structure of haem The iron
• The iron in the haem is in ferrous (Fe2+) form.
• The iron is attached to the nitrogen atom of each
pyrrole ring.
• On the iron a bond is available for loose union, were O 2
is attached. Structure of haem Attachment of haem to globin
• One molecule of Hb contains four units of haem, each
attached to one of the four polypeptide chains constituting globin.
• As there are four units of haem in one molecule of Hb,
so there are four iron atoms in one molecule of Hb which can carry four molecules of oxygen Structure of Hb Synthesis of Hb Functions of Hb • Transport of Oxygen
• Transport of CO2
• Control pH of the blood
Physiological varieties of haemoglobin • Haemoglobin A HbA (α2β2)
• Haemoglobin A2 HbA2 (α2δ2)
• Haemoglobin F HbF (α2γ2)
Haemoglobinopathies • Abnormal formation of Hb occurs due to the disorders of globin synthesis; haem synthesis being normal. • Disorders of the globin synthesis are of two main types: • Formation of abnormal polypeptide chains due to substitution of an abnormal amino acid chain in the HbA as seen in sickle cell anaemia • Suppression of synthesis of polypeptide chain of globin as seen in thalassaemia. Sickle cell haemoglobin • HbS is formed due to substitution of valine for glutamic acid at position 6 in the β chain of HbA.
• When HbS is reduced (e.g. in low O 2 tension or when pH
at tissue level is low), it becomes much less soluble and precipitates into crystals within the RBCs.
• The crystals elongate producing changes in shape of the
cells from biconcave to sickle-shaped cells (sickling). Sickle cell haemoglobin • Cells containing HbS are less flexible as compared to the RBCs containing HbA, leading to a blockade of microcirculation.
• Sickle-shaped cells are more fragile and are very liable
to undergo hemolysis producing sickle cell anemia Sickle cell haemoglobin • Sickle trait is inherited as Mendelian dominant but the full blown disease is autosomal recessive.
• Heterozygous individual with sickle cell trait rarely has
severe symptoms but homozygous develop full blown disease.
• The individual with sickle cell trait has resistance to one
type of malaria. Thalassaemia • Thalassaemia results due to defect in the synthesis of polypeptide chain α and β of HbA.
• Depending upon whether α or β chains are not
synthesized, α thalassaemia or β thalassaemia may occur, respectively.
• β Thalassaemia is more common and is further of two
types: thalassaemia major and thalassaemia minor Derivatives of Hb • Oxyhaemoglobin (Hb + O2) • Reduced hemoglobin or deoxygenated hemoglobin • Carbamino-haemoglobin (Hb + CO2) • Carboxyhaemoglobin or carbon monoxyhemoglobin (Hb + CO) • Methaemoglobin [ferrous (Fe2+) is oxidized to ferric (Fe3+)] • Glycosylated haemoglobin (HbA1C) - glucose is attached to terminal valine in the β chains. Thank You
