TYPES OF HEMOGLOBINS & HEMOGLOBINOPATHIES

Slides:



Advertisements
Similar presentations
Role of iron deficiency anemia in the propagation of beta thalassemia gene Usman, M., Moinuddin, M., Ahmed, S.A. (2011) Korean J Hematol 46: Microcytic.
Advertisements

Red Cells Prof. K. Sivapalan. June 2013Red Cells2 ERYTHROCYTE- RBC Biconcave disc. 7.2 μ x 2.2 μ No nucleus. PCV – 45, 35 % Hb% - –14.5 g/dL. - Males,
Protein Function Globins and Antibodies 3/12/2003.
Quantitation of Methemoglobin
Thalassemia & Treatment
MLAB Hematology Keri Brophy-Martinez Chapter 6: Hemoglobin.
Hemoglobin Structure & Function
Hemoglobin Determination. Hemoglobin — Found in the RBC. — Responsible for carrying oxygen to all cells in the body. — Also binds to carbon dioxide and.
Hemoglobin (Hb) Hb is found in RBCs its main function is to transport O2 to tissues. Structure: 2 parts : heme + globin Globin: four globin chains (2 α.
Dr. Nasim.  Hemeproteins are a group of specialized proteins that contain heme as a tightly bound prosthetic group  hemoglobin and myoglobin, the two.
1 Respiratory system L4 Faisal I. Mohammed, MD, PhD University of Jordan.
DR AMINA TARIQ BIOCHEMISTRY
Hemoglobin Structure & Function
SCDAA 40 th Anniversary Convention 2012 Genetic Counseling for the Future Kwaku Ohene-Frempong, MD Children’s Hospital of Philadelphia Sickle Cell Foundation.
Respiratory Block | 1 Lecture Dr. Usman Ghani
P. Pathophysiology Normally, the majority of adult hemoglobin (HbA) is composed of four protein chains, two α and two β globin chains arranged into.
Hemoglobin (Hb) Hb is found in RBCs its main function is to transport O2 to tissues. Structure: 2 parts : heme + globin Globin: four chains. Heme: porphyrin.
Anemia Dr Gihan Gawish.
Investigating haemoglobinopathies. Carrier frequencies of thalassaemia alleles (%) Regionβ-Thalassaemiaα 0 -Thalassaemiaα + -Thalassaemia Americas 0–30–50–40.
Hemoglobin Electrophoresis
MLAB 1415: Hematology Keri Brophy-Martinez
Hemoglobin Structure & Function. Objectives of the Lecture structuralfunctional 1- Understanding the main structural & functional details of hemoglobin.
Structure and function of hemoglobin
Hemoglobin Concentration Determination
Blood Disorders. Methemoglobinemia a disorder characterized by the presence of a higher than normal level of methemoglobin (metHb) in the bloodmethemoglobinblood.
Hemoglobin Structure & Function
Thalassemia & Treatment. What is thalassemia? Genetic blood disorder resulting in a mutation or deletion of the genes that control globin production.
Practical Hematology Lab
Sickle cell Anaemia. What is it? The Hemoglobin protein in blood is effected This protein, which is different because of the iron found in it, is responsible.
Lecture 4 Topic 2. Gene Function & Gene Expression.
INHERITED TRAITS THAT HAVE MAJOR EFFECTS ON HEALTH Nutrition and Gene Expression Jan 23, 2014.
Myoglobin •Site: muscles
THALASSAEMIA Konstantinidou Eleni Siligardou Mikela-Rafaella.
Variant types of Haemoglobinopathies
MLAB 1415: Hematology Keri Brophy-Martinez
HEMOGLOBIN (Hb) Structure of Hb The red, oxygen-carrying pigment in the red blood cells is hemoglobin, a protein with a molecular weight of 64,450.Hb is.
Genetic Counseling for the Future
Hemoglobin (Hb) Hb is found in RBCs its main function is to transport O2 to tissues. Structure: 2 parts : heme + globin Globin: four chains. Heme: porphyrin.
Oxygen Transport by Blood LECTURE 20 By Dr. Khaled Khalil Assistant Professor of Human Physiology.
Globular Proteins Respiratory Block | 1 Lecture. Objectives To describe the globular proteins using common examples like hemoglobin and myoglobin. To.
GENETIC DISEASES Lecture 5
Mark D. Browning, M.D. March 10, 2016
 Heme proteins meaning.  Structure and function of myoglobin.  Structure and function of hemoglobin.  Types of hemoglobin.  Oxygenation & deoxygenation.
Hemoglobin Structure & Function. Objectives of the Lecture structuralfunctional 1- Understanding the main structural & functional details of hemoglobin.
Dr. Shumaila Asim Lecture # 4
Lec. 3 NOV 2016.
Respiratory Block | 1 Lecture
Respiratory Block | 1 Lecture
Dr. Shumaila Asim Lecture #6
Haemoglobin its structure, functions, types and abnormalities
GLOBULAR HEMOPROTEINS
Anemia By: Dr Sunita Mittal.
Miss.Shuchismita Behera Miss.Sujata Dixit Dr.G.Bulliyya Dr.S.K.Kar
Faisal I. Mohammed, MD, PhD
Molecular basis of hemoglobinopathies
Hemoglobinopathies Dr Sunita Mittal.
Lecturer of Medical Biochemistry
Unexpected Hemoglobin A 1c Results Dr.M.KOTTESWARAN 1 ST YEAR BIOCHEMISTRY PG.
Hemoglobinopathies in Pregnancy
Hemoglobin metabolism & diseases of hemoglobin
Structure, function and metabolism of hemoglobin
Introduction To Medical Technology
Estimation of Hemoglobin
Case Summary John a 4 year old boy ,complains of
QUANTITATION OF METHEMOGLOBIN
Hemoglobin Concentration Determination
Respiratory Block | 1 Lecture
Hemoglobin Concentration Determination
Respiratory Block | 1 Lecture
The Functional Diversity of Proteins: The Example of Hemoglobin
Presentation transcript:

TYPES OF HEMOGLOBINS & HEMOGLOBINOPATHIES BIOCHEMISTRY DR AMINA TARIQ

Types in humans In the embryo: Gower 1 (ζ2ε2) Gower 2 (α2ε2) Hemoglobin Portland (ζ2γ2)

In the fetus: Hemoglobin F (α2γ2)

In Adults : Hemoglobin A (α2β2) - The most common with a normal amount over 95% Hemoglobin A2 (α2δ2) - δ chain synthesis begins late in the third trimester and in adults, it has a normal range of 1.5-3.5%

Hemoglobin F (α2γ2) - In adults Hemoglobin F is restricted to a limited population of red cells called F-cells. However, the level of Hb F can be elevated in persons with sickle-cell disease.

Variant forms which cause disease: Hemoglobin H(β4) - A variant form of hemoglobin, formed by a tetramer of β chains, which may be present in variants of α thalassemia. Hemoglobin Barts (γ4) - A variant form of hemoglobin, formed by a tetramer of γ chains, which may be present in variants of α thalassemia.

Hemoglobin C (α2βC2) - Another variant due to a variation in the β-chain gene. This variant causes a mild chronic hemolytic anemia. Hemoglobin E (α2βE2) - Another variant due to a variation in the β-chain gene. This variant causes a mild chronic hemolytic anemia.

Hemoglobin S (α2βS2) - A variant form of hemoglobin found in people with sickle cell disease. There is a variation in the β-chain gene, causing a change in the properties of hemoglobin which results in sickling of red blood cells.

Genetics The sequences of hemoglobins differ between species. Even within a species, different variants of hemoglobin exist. For example, mutations in the genes for the hemoglobin protein in a species result in hemoglobin variants, some of these mutant forms of hemoglobin cause a group of hereditary diseases termed the hemoglobinopathies.

The best known is sickle-cell disease, which was the first human disease whose mechanism was understood at the molecular level. A separate set of diseases called thalassemias involves underproduction of normal and sometimes abnormal hemoglobins, through problems and mutations in globin gene regulation. All these diseases produce anemia.

The iron ion may either be in the Fe2+ or Fe3+ state, but methemoglobin (Fe3+) cannot bind oxygen. In binding, oxygen temporarily oxidizes (Fe2+) to (Fe3+), so iron must exist in the +2 oxidation state to bind oxygen. The enzyme methemoglobin reductase reactivates hemoglobin found in the inactive (Fe3+) state by reducing the iron center.

The absorption spectra of oxyhemoglobin and deoxyhemoglobin differ The absorption spectra of oxyhemoglobin and deoxyhemoglobin differ. The oxyhemoglobin has significantly lower absorption of the 660 nm wavelength than deoxyhemoglobin, while at 940 nm its absorption is slightly higher.

This accounts for hemoglobin's red color and deoxyhemoglobin's blue color. This difference is used for measurement of the amount of oxygen in patient's blood by an instrument called pulse oximeter.

Hemoglobin AS - A heterozygous form causing Sickle cell trait with one adult gene and one sickle cell disease gene Hemoglobin SC disease - Another heterozygous form with one sickle gene and another encoding Hemoglobin C.

Role in disease Hemoglobin deficiency can be caused either by decreased amount of hemoglobin molecules as in anemia, or decreased ability of each molecule to bind oxygen at the same partial pressure of oxygen. Hemoglobinopathies(genetic defects resulting in abnormal structure of the hemoglobin molecule) may cause both.

There is a group of genetic disorders, known as the Porphyrias that are characterized by errors in metabolic pathways of heme synthesis.

To a small extent, hemoglobin A slowly combines with glucose at the terminal valine (an alpha aminoacid) of each β chain. The resulting molecule is often referred to as Hb A1c. As the concentration of glucose in the blood increases, the percentage of Hb A that turns into Hb A1c increases.

In diabetics whose glucose usually runs high, the percent Hb A1c also runs high. Because of the slow rate of Hb A combination with glucose, the Hb A1c percentage is representative of glucose level in the blood averaged over a longer time (the half-life of red blood cells, which is typically 50–55 days).

The levels of glycosylated hemoglobin are tested to monitor the long-term control of the chronic disease of type 2 diabetes mellitus (T2DM). Poor control of T2DM results in high levels of glycosylated hemoglobin in the red blood cells.

The normal reference range is approximately 4 %–5. 9 % The normal reference range is approximately 4 %–5.9 %. Though difficult to obtain, values less than 7 % are recommended for people with Type 2 DM. Levels greater than 9 % are associated with poor control of the glycosylated hemoglobin and levels greater than 12 % are associated with very poor control.

Diabetics who keep their glycosylated hemoglobin levels close to 7 % have a much better chance of avoiding the complications that can sometimes accompany diabetes (than those whose levels are 8 % or higher).

Diagnostic uses Hemoglobin concentration measurement is among the most commonly performed blood tests, usually as part of a complete blood count.

Normal levels are: Men: 13.8 to 17.2 g/dl Women: 12.1 to 15.1 g/dl Children: 11 to 16 g/dl Pregnant women: 11 to 12 g/dl