Hemoglobin Synthesis PDF

Definition Haemogolobin is considered as specialized conjugated protein, have M.W of 64000 (oxygen carrying protein)  Each RBC contain approximately 640 million of Hb molecules , make up about 60% of dry weight of red cell Hemoglobin What is it? Iron- bearing p...

Definition Haemogolobin is considered as specialized conjugated protein, have M.W of 64000 (oxygen carrying protein)  Each RBC contain approximately 640 million of Hb molecules , make up about 60% of dry weight of red cell Hemoglobin What is it? Iron- bearing protein which is the main component of the RBC Gives the red cell its color Synthesis Majority synthesized at the polychromatophilic normoblast stage Regulation Stimulated by tissue hypoxia Hypoxia causes the kidneys to increase production of EPO, which increases RBC and hemoglobin production Function Carry oxygen from the lungs to the tissues Remove CO2 Buffering action, maintains blood pH as it changes from oxyhemoglobin (carrying O2) to deoxyhemoglobin ( without O2) Hemoglobin Reference Ranges Adults Male 14-17.4 g/dL Female12-16.0 g/dL Children Birth 13.5-20.0 g/mL 6-12 years 11.5-15.5 g/mL Structure 4 polypeptide Subunits Heme group Porphyrin ring Ferrous iron Globin chain 2 Alpha Chains 2 Beta chains Hemoglobin Synthesis Synthesis Occurs in the mitochondria of developing red cells as they mature in the bone marrow Processes necessary for normal synthesis Adequate iron supply & delivery Adequate synthesis of protoporphyrins Adequate globin synthesis Haemoglobin synthesis 65% of the Hb is synthesized in the erythroblasts, and 35% at the reticulocyte stage. Haem synthesis occurs largely in the mitochondria. Globin synthesis occurs in the polyribosomes. Although haem and globin synthesis occur separately within developing red cell precursors, their rates of synthesis are carefully coordinated to ensure optimal efficiency of Hb assembly. Heme Synthesis Chain of Events Iron delivery & supply Iron is delivered to the reticulocyte by transferrin Synthesis of protoporphyrins Occurs in the mitochondria of RBC precursors Mediated by EPO and vitamin B6 Protoporphyrin + iron = heme Globin synthesis The various globins that combine with haem to form Hb are all single chain polypeptides. The synthesis of these globins is under genetic control. Humans normally carry eight functional globin chains, arranged in two, duplicated gene clusters: the b-like cluster (b, g, d and e globin genes) on the short arm of chromosome 11 and the a-like cluster (a and z globin genes) on the short arm of chromosome 16. Globin Synthesis Chain of Events The rate of globin synthesis is proportional to the rate of porphyrin synthesis. Proper globin synthesis depends on genes. The precise order of amino acids in the globin chains is critical to the structure and function of hemoglobin. Chain designations are as follows Alpha α, beta β, delta δ, epsilon ε, gamma γ, zetaζ Normal hemoglobins Embryonic Fetal Adult Hemoglobins hemoglobin hemoglobins Gower 1- zeta Hemoglobin F- Hemoglobin A- (2), epsilon (2) alpha(2), alpha (2), beta gamma (2) (2) Gower 2- alpha ~95% (2), epsilon (2) Hemoglobin A2- alpha(2), delta(2) Portland-Zeta (2), gamma (2) ~1.5-3.7% Hemoglobin F- alpha(2), gamma (2) 5 g/dl deoxyhemoglobin in blood Patient appears blue Nonfunctional hemoglobins Carboxyhemoglobin Oxygen molecules bound to heme are replaced by carbon monoxide. Slightly increased levels of carboxyhemoglobin are present in heavy smokers and as a result of environmental pollution. Can revert to oxyhemoglobin. Methemoglobin Iron in the hemoglobin 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 to an enzyme deficiency (more discussion to follow). Can revert to oxyhemoglobin Sulfhemoglobin Hemoglobin molecule contains sulfur. Caused by certain sulfur-containing drugs or chronic constipation. Cannot revert to oxyhemoglobin and may cause death.  Normal red cell breakdown haemoglobin haem globin iron protoporphyrin Amino acids CO Bilirubin transferrin Expired air (free) Liver conjugation erythroblast Bilirubin glucuronides Urobilin(ogen) Stercobilin(ogen) Urine faeces Haemoglobin abnormalities There are mainly two types of abnormalities, these are : Quantitative abnormalities: where there is reduction in the production of certain types of globins e.g. a thalassaemia b thalassaemia Qualitative abnormalities: where there is production of abnormal haemoglobin e.g. sickle cell anaemia. References McKenzie, S. B. (2010). Clinical Laboratory Hematology (2nd ed.). Upper Saddle River, NJ: Pearson Education, Inc..