Hb-synthesis 3.57.51 PM

Hb-synthesis 3.57.51 PM - Haemoglobin synthesis &...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Haemoglobin synthesis & catabolism catabolism Dr. Suhair Abbas Ahmed Haemoglobin synthesis Haemoglobin The haemoglobins are red globular proteins, which have a molecular weight of about 68,000 and comprise almost one third of the weight of a red cell. the The haemoglobin is composed of haem and globin. globin. Haemoglobin synthesis Haemoglobin The main function of red cells is to carry O2 to the tissues and to return carbon dioxide (CO2) from tissues to the lungs. (CO In order to achieve this gaseous exchange In the red cells contain the specialized protein haemoglobin. haemoglobin. Each red cell contains approximately 640 Each million Hb molecules. million Haemoglobin synthesis Haemoglobin 65% of the Hb is synthesized in the erythroblasts, 65% and 35% at the reticulocyte stage. and Haem synthesis occurs largely in the Haem mitochondria. mitochondria. Globin synthesis occurs in the polyribosomes. Although haem and globin synthesis occur Although separately within developing red cell precursors, their rates of synthesis are carefully coordinated to ensure optimal efficiency of Hb assembly. ensure Globin synthesis Globin The various globins that combine with haem to The form Hb are all single chain polypeptides. form The synthesis of these globins is under genetic The control. control. Humans normally carry eight functional globin Humans chains, arranged in two, duplicated gene clusters: the β-like cluster (β, γ , δ and ε globin genes) on the short arm of chromosome 11 and the α-like -like cluster (α and ζ globin genes) on the short arm of cluster chromosome 16. chromosome Ontogeny of globin synthesis Ontogeny Globin synthesis is first detected in the primitive erythroid precursors of the yolk sac at about 3 weeks’ gestation. weeks’ Embyonic : Haemoglobin Gower I ( ζ2ε2) Haemoglobin Portland ( ζ2γ 2) Haemoglobin Gower II (α2ε2 ) Haemoglobin Fetal : HbF (α2γ 2), HbA (α2β2) Adult : HbA, HbA2 ( α2δ2), HbF. Adult Haemoglobin Each molecule of Each normal adult haemoglobin (Hb-A) consists of four polypeptide chains α2 β2 , each with its own each haem group. haem Haemoglobin Haemoglobin Normal adult blood also contains small Normal quantities of two other haemoglobins, Hb-F and Hb-A2. These also contain chains but chains and These with γ and chains respectively instead of β. The major switch from fetal to adult The haemoglobin occurs 3-6 months after birth. haemoglobin Normal Hb in adult blood Normal Hb A Hb A2 Hb F structure 2β2 22 2γ 2 Normal % 96-98 % 1.5-3.2 % 0.5-0.8 % Haemoglobin synthesis Haemoglobin Haem synthesis starts with Haem the condensation of glycine and succinyl coenzyme A under the action of a rate limiting enzyme δ-aminolaevulinic -aminolaevulinic acid synthase. acid δ-ALA will be formed. Pyridoxal phosphate (vit. Pyridoxal B6) iis a coenzyme for this s reaction. reaction. Haemoglobin synthesis Haemoglobin A series of biochemical series reactions will follow. reactions Two molecules of δ-ALA Two -ALA condense to form a pyrrole called porphobilinogen (PBG) (PBG) Four PBG condense to Four form a tetrapyrrole uroporphyrinogen III. uroporphyrinogen UPG III is then converted UPG to coproporphyrinogen. Haemoglobin synthesis Haemoglobin CPG then changes to CPG protoporphyrin which ultimately combines with iron in the ferrous state (Fe2+) to form haem. (Fe Iron is brought to the Iron developing red cells by a carrier protein ( transferrin) which attaches to special binding sites on the surface of these cells. surface Transferrin releases iron Transferrin and returns back to circulation. circulation. Haemoglobin synthesis Haemoglobin Each molecule of Each haem combines with a globin chain. globin A tetramer of four tetramer globin chains each with its own haem group in a pocket is formed to make up a haemoglobin molecule. haemoglobin Haemoglobin structure Haemoglobin Haem consists of a Haem protoporphyrin ring with an iron atom at its centre. iron The protoporphyrin ring The consists of four pyrrole groups which are united by methane bridges (=C-). methane The hydrogen atoms in the The pyrrole groups are replaced by four methylene (CH3-), two vinyl (-C=CH2) and two propionic acid (-CH2-CH2propionic COOH) groups. Haemoglobin catabolism Haemoglobin *normal red cell destruction* Red cell destruction usually occurs after a mean Red life span of 120 days. The cells are removed extravascularly by The macrophages of the reticuloendothelial system (RES), specially in the bone marrow but also in the liver and spleen. liver Red cell metabolism gradually deteriorates as Red enzymes are degraded and not replaced, until the cells become non viable, but the exact reason why the red cells die is obscure. Haemoglobin catabolism Haemoglobin *normal red cell destruction* The breakdown of red cells liberates 1- iron for recirculation via plasma transferrin 1to marrow erythroblasts to 2- protoporphyrin which is broken down to 2bilirubin. bilirubin. 3- globins which are converted to amino 3acids. Normal red cell destruction Normal - The bilirubin circulates to the liver where it is The conjugated to glucuronides which are excreted into the gut via bile and converted to stercobilinogen and stercobilin(excreted in faeces). in - Stercobilinogen and stercobilin are partly Stercobilinogen reabsorbed and excreted in urine as urobilinogen and urobilin. urobilinogen Normal red cell destruction Normal A small fraction of protoporphyrin is small converted to carbon monoxide (CO) and excreted via the lungs. excreted Globin chains are broken down to amino Globin acids which are reutilized for general protein synthesis in the body. synthesis Normal red cell breakdown haemoglobin haem iron transferrin erythroblast Urobilin(ogen) Urine globin protoporphyrin CO Expired air Amino acids Bilirubin (free) Liver conjugation Bilirubin glucuronides Stercobilin(ogen) faeces Haemoglobin abnormalities Haemoglobin There are mainly two types of abnormalities, these are : these Quantitative abnormalities: where there is Quantitative reduction in the production of certain types of globins e.g. α thalassaemia β thalassaemia thalassaemia Qualitative abnormalities: where there is Qualitative production of abnormal haemoglobin e.g. sickle cell anaemia. sickle ...
View Full Document

Ask a homework question - tutors are online