Biochemistry Sheet 23 PDF

23 Nahla Ayad Wedad Mustafa & Waqar Alfaqeer Dr. Nafez 1 Abutarboush  Hemoglobinopathies Hemoglobinopathies: diseases related to hemoglobin Globin Genes: When hemoglobin is produced first the globin protein is produced and then the heme group is added...

23 Nahla Ayad Wedad Mustafa & Waqar Alfaqeer Dr. Nafez 1 Abutarboush  Hemoglobinopathies Hemoglobinopathies: diseases related to hemoglobin Globin Genes: When hemoglobin is produced first the globin protein is produced and then the heme group is added to it. Hemoglobin has 2 gene families (alpha and beta), since 2 different subunits so different genes. The alpha gene family is located on chromosome 16 and has 2 genes for the alpha – globin chains and others ( remains on throughout life) each of gene has 2 alleles= 4loci for synthesizing hemoglobin. The beta gene family is located on chromosome 11 and has a single gene for beta -globin chain. Chromosome 11 also has 2 gamma and the delta gene. Alpha genes takes part in embryonic, fetal, minor and major adult globin proteins Beta gene takes part in major adult globin proteins Delta takes part in minor adult and makes HbA2 Gamma takes part in the fetal globin protein Are they serious? 2 They are serious and one of the most common inherited diseases worldwide Hemoglobinopathies: is disorders of the human hemoglobin and it is the most common genetic disease group in the world where about 5% of people are carriers, causing substantial morbidity where about 300000 born each year. Hereditary disorders are either: 1. Qualitative: where the mutation affects the quality of the structure resulting in structural variants 2. Quantitative: where the mutation affects the number of subunits( amounts of alpha and beta) resulting in imbalance in the alpha to beta ratio. (Normal ration= 2alpha:2 beta). Hereditary persistence of fetal hemoglobin (HPFH): impairment of the perinatal switch from γ to β globin Qualitative abnormalities Sickle cell hemoglobin (HbS) Here in the amino acid chain in beta subunit amino acid number 6 which is in normal cells Glu is replaced by Val (Glu6 toVal6) ,making aggregates of hemoglobin at low oxygen tension where Pa O2