Hemoglobin Gene Organization And Hemoglobin Disorders (Lec 8)

Effect of carbon monoxide (CO) on the oxygen affinity of hemoglobin

How does the CO (carbon monoxide) regulate

• The carbon monoxide is so tiny it binds so slowly and stabilizes the R state

• It is converted to myoglobin-like behavior

• when the hyp

• Carbon dioxide facilitates the R state

Carbon monoxide (CO) has 2 or 3 times more affinity to iron (Fe) than oxygen (O2)

Myoglobin and Hemoglobin belongs to a protein family

Hemoglobin is very similar and belongs to a protein family

• have minor changes int he AA composition just the primary structure of the protein

The change in the AA can completely change the ability of being regurgitated

Divertion evolution: starts w. one protein and it is diverted into new proteins with diff functions, but the primary structure is kept the same

• one or t2o AA changes can change the functions

Globin gene clusters and expression during development

Multiple different versions of fetal hemoglobin w. different affinities towards O2

• fetal hemoglobin does not have beta changes

• both globin family of genes encodes these diff variations of the hemoglobin

fetal hemoglobin is that alph beta, there are variaitons ot the alpha changes, and its afifnity of xogyen is regualted by its compositon of genes, and it is expressed in the hemoglobin structure throughg gene shuffling

Hemoglobinopathies

genetic disorders produced by strucutrally abnormal hemoglobin moelcule

Polymerization of deoxyhemoglobin S

Hemoglobin just out of the blood cells by making a long hydrophibic interaction that polumerizzes hemoglobin

Hemoglobinopathies: Sickle cell anemia (HbS)

Sickle cell is found in various areas of the world

The assumption is that sickle cell is a genetic adaption of how to restrain malaria in these populations (Africa)

• in regions where malaria is very common in the world, the ppl hjave these types of traits as a genetic adaption for resiting the malaria disease

Hemoglobinopathies: Hemoglobin C disease

Hemoglobin C —> it is amutation

• this mutation has 2 effects

• active transport

• has a normal conc. of hemoglobin in the cells

• when there is a high conc. in a very confined area → they percipiatate becauses of the excess

Percipiataiton of hemologbin in the cells → when perciipiated there is no use for it

Hemoglobinopathies: Methemoglobinemia (HbM

The Fe+3 state does not have any affinity for oxygen

certain molecule has to be kept in a certain oxidation state

Hemoglobin Fe+2 becomes methmoglobin Fe+3

• it is oxidized and Fe3+ cant bind to oxygen

• caused by rare mutations sin the a or b globin chain

Blue coloration of the skin is indiation of deoxy hemologbin

Hemoglobinopathies: Thalassemias

Every one caries 2 alpha and 2 beta chains —> any chainges to these ratios leads to an inability of carrying the function it is suppsoed to carry

A-thalasemia: where the aplha chain is silent not produced engough

• does not have an alpha chain

B-thaalsemia: does not have a beta chain

Changes in the structure results in perciptating and loss of RBCs can lead to aneia

GLYCATED HEMOGLOBIN (HbA1c)

A1c levels show glucose fluctuation in blood

• high

• normal glucose levels of 5 MM concentration

• Glucose can attach to the hemoglobin and store it/ have it circulating for many weeks