Haemoglobin Synthesis Lecture Notes PDF

Introduction to Haemoglobin GAVIN KNIGHT Learning Objectives On completion of this session, you should be able to: 1. Describe how the haemoglobin molecule is formed 2. Describe the basic structure of haemoglobin 3. Recognise the consequences of selected defects in haemoglobin...

Introduction to Haemoglobin GAVIN KNIGHT Learning Objectives On completion of this session, you should be able to: 1. Describe how the haemoglobin molecule is formed 2. Describe the basic structure of haemoglobin 3. Recognise the consequences of selected defects in haemoglobin synthesis 4. Identify the principal haemoglobin measurements included within the Full Blood Count Introduction  Red cells carry O2 from the lungs to the tissues, and CO2 back to the lungs  Approx. 98% of the cytoplasmic protein is Hb  65% of Hb is made prior to the extrusion of the nucleus  Haemoglobin is a metalloprotein  Haemoglobin is primarily reported in the following FBC measurements:  Haemoglobin  Mean Cell Haemoglobin (MCH) - range: 27 – 32 pg  Mean Cell Haemoglobin Concentration (MCHC) - range 315 – 345 g/L Basic Structure 1) Heterodimeric tetramer 2) Comprises two -like globin chains and two non- globin chains 3) Haem group Image: https://askhematologist.com/abnormal-hemoglobins/ Haemoglobin synthesis Glycine + Succinyl CoA Haem ALA Globin Iron + synthase + ferrochelatas -aminolaevulinic e Protoporphyrin acid IX Protoporphyrinogen Porphobilinogen synthase oxidase porphobilinogen Protoporphyrinogen IX HMB synthase Haemoglob Coproporphyrinog en- decarboxylase hydroxymethylbilane in Coproporphyrinoge CYTOPLASM n III Uroporphyrinogen I Uroporphyrinogen Uroporphyrinogen III synthase decarboxylase Uroporphyrinogen III synthase Porphyrias An overview of the cutaneous porphyrias - Scientific \ Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Simplified- porphyria-haem-biosynthetic-pathway-illustrating- the-enzyme-defects-decreased_fig1_320718288  Haem Iron is chelated into protoporphyrin IX by ferrochelatase to form the final haem molecule. Remember the ion present at the centre of Haem may be in different states. https://derangedphysiology.com/main/cicm-primary-exam/ required-reading/haematological-system/Chapter%20011/ mage: Yikrazuul / Public domain https://commons.wikimedia.org/wiki/File:Heme_b.svg structure-and-function-haemoglobin  Summary  The majority of haemoglobin is synthesised prior to the reticulocyte stage of maturation  Haemoglobin is a heterodimeric tetramer which, beyond the embryonic stage of maturation, requires the presence of α chains  Synthesis of haemoglobin occurs within the cytoplasm (on ribosomes) and within mitochondria.  Ferrochelatase incorporates iron into haem subunits  Haem is located towards the periphery of the globin chains