Iycee Charles de Gaulle Summary Protein Defects That Can Be Associated With The Red Blood Cell Biology Essay

Protein Defects That Can Be Associated With The Red Blood Cell Biology Essay


Red blood cells are the largely found cell in blood.

Their chief map is to transport O around the whole organic structure. Tissues and organic structure variety meats are all depend on the RBC ‘s to provide them with O. If the circulation is blocked the tissue dies. Red blood cells are besides known as “ red blood cell ” which means “ ruddy hollow ” from Greek. Red blood cells attains its ruddy coloring material from haemoglobin that constitute about 97 % of the RBC ‘s dry weight, and about 35 % of the whole weight, with H2O.Hemoglobin is a metalloprotein that is iron-rich and has many chemical apertures for O storage.

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This characteristic allows haemoglobin to transport a big sum of O2 for distribution. Red blood cells become oxygenated in the lungs, and back to the bosom where the flow starts to the appendages. Harmonizing to Moore et Al ( 2010 ) “ Red blood cells lack a karyon, chondriosomes and they are much dilutant in the in-between organizing a concavo-concave form.

Therefore they have the ability to go through the smallest capillaries ” . Without this nature of flexibleness, they have a high opportunity of acquiring stuck and cause obstructors in the circulation.The ruddy blood cell varies in size and coloring material. They are about 7um in diameter. Deoxygenated blood has blue colour, while oxygenated blood expressions ruddy. The 2nd of import map to transporting O and less known is the capableness of ruddy blood cells to transport C dioxide that is formed due to metamorphosis in every cell in the human organic structure.The construction and constituents of the ruddy blood cell membrane are responsible for the physiological maps and mechanical belongingss of the cell. A defect in any of these constituents may do a disfunction of RBC taking to serious disease.

The ruddy cell membrane consists of dual lipid bilayer, assorted proteins and an internal membrane skeleton which provides the RBC with its biconcave form. The skeleton is formed by a multi-protein complex including alpha and beta spectrin, ankyrin, protein 4.1 and actin.

Fig 1: The ruddy blood cell membrane construction. [ 1 ]The above diagram shows the ruddy cell membrane exemplifying the interaction between phospholipids and the proteins. Horizontally, alpha and beta spectrin of the cytoskeleton interact organizing tetramers which so becomes linked to the cytoplasmatic domin of set 3 by ankyrin ( ventricle interaction ) .

The 4.1 protein heighten the interaction between set 3 and ankyrin. The ends parts of the tetramers are so interact to actin, tropomodulin, tropomyosin and adducin.


Normal ruddy blood cells are deformable concave discs. The external environment of the cell, the metabolic activity of the cell, the nature of haemoglobin, the membrane skeleton and the age of the cell find the form of the cell. Cavendish ( 2008:13 ) stated that “ The ruddy blood cells last about 120 yearss, until they are finally removed by the lien ” .

If the RBCs tend to acquire destroyed really rapidly than usual by disease, so the bone marrow will bring forth to counterbalance the lost cells to take the topographic point of new ruddy cells. But if RBCs are deformed by any ground the individual can endure from assorted diseases. Some defects in ruddy cell membrane proteins have been observed as follows ; ( 1 ) spectrin lack entirely, ( 2 ) combined spectrin and ankyrin lack, ( 3 ) set 3 lack, and ( 4 ) protein 4.2 defects. ( 5 ) protein 4.1 lack.Table 1: Protein lack associated with ruddy blood cells and familial information

Protein Defect


Familial Information

Spectrin lackFamilial elliptocytosis-Hereditary elliptocytosis ( HE ) is aA inborn haemolytic upset in which erythrocytes get elongated into a cigar or egg-shaped form.

-Chromosome location 1q22-q23.-Mutations that obstruct the formation of spectrin tetramers result in familial elliptocytosis.-Symptoms are haemolytic anaemia, gall rocks and weariness.Ankyrin lackFamilial Spherocytosis-Hereditary spherocytosis is a inborn hemolytic anaemia caused by a defect in several proteins including ankyrin.-Chromosome location: 8p11A·2-Symptoms are Severe anemia, icterus, splenomegaly and cholelithiasis.

Band 3 lackSickle cell disease-Sickle cell disease possesses ruddy blood cells that consist of unnatural haemoglobins ( oxygen ill ) , organizing a crescent form cells.-Chromosme location: 11p15.5.-Sickle cells are destroyed rapidlyin the accomplished single causation anaemia, icterus and the formation of bilestones plus to other clinical characteristics.

Protein 4.1 lackHemolytic anaemiaPolycystic kidney disease-In the cause of haemolytic anaemia, the RBC ‘s are destroyed and excreted from the blood stream before their usual life-time.-Chromosome Location: 1p36 – 2p34.-Symptoms: weariness, arrhythmias ( ah-RITH-me-ahs ) , hurting, megalocardia and high hematoidin in plasma.Protein 4.

2 lackSplenomegaly-In splenomegal the lien is enlarged. This can take to cirrhosis and chronic infections.-Hypersplenism is observed in patients with splenomegaly and besides cytopenias and anaemia.-Chromosome Location q15-q21Glycphorin C lackOvalocytosis-In familial ovalocytosis, the blood cells are somewhat egg-shaped alternatively of unit of ammunition.-Symptoms: in new born babies anaemia and icterus are common. While in grownups, it ‘s symptomless.

Diseases caused by protein defect in ruddy blood cells

G6PD lack.Glucose-6-phosphate dehydrogenase lack is the most common familial upset worldwide.

This status is caused due to the deficiency of the enzyme G6PD or a lessening in the production. The defect in doing this enzyme may take to impaired production of the molecules NADPH and NADP impacting the metabolic tracts in the human organic structure. A lessening in the coevals of NADPH molecules can impact the degree of glutathione ( GSH ) go forthing RBC ‘s exposed to the toxic effects of O2, which in bend lead to the dislocation of RBC ‘s prematurely ( haemolysis ) . The G6PD cistron is located in the X chromosome at the q28 venue ( Moore et Al, 2010 ) . Mehta and co-workers stated that conditions such as electrolyte instability, membrane cross bonding and red blood cellPhagocytosis, are consequences of G6PD lack. G6PD lack is a widely seen familial disease among people of African, Southeast Asian and Mediterranean descent.

Harmonizing to Smith ( 2004:56-60 ) ” G6PD is found among people who live, or whose ascendants lived in parts of universe where malaria is, or has been, endemic ” .Peoples with Glucose-6-phosphate dehydrogenase lack may develop chronic haemolytic anaemia every bit good as icterus in new born. Other factors can besides bring on the haemolytic anaemia such as infections and drugs.Familial SpherocytosisFamilial spherocytosis is a upset in which ruddy blood cells lose their visual aspect bring forthing spherical like form, and becomes delicate due to the instability of the cytoskeleton in the ruddy cell membrane ensuing from several mutants in the membrane proteins that are involved in the perpendicular interaction such as ankryn, spectrin ( I± and I? ) , band 3 and protein 4.2.

These unit of ammunition and fragile cells have a reduced lifetime ( between 6-20 yearss ) comparing to 120 yearss in normal RBCs and have a trouble to go through through certain variety meats ( splenetic microcirculation ) . Therefore, they remain in the lien longer than normal ruddy blood cells, taking to spleen harm. This membrane harm can cut down the cellular deformability every bit good as the membrane surface to volume ratio.Fig 2: The consequence of familial SpherosytosisDiagram obtained from Perrotta et Al ( 2008 ) quoted from Gallagher and co-workers.Perrotta et Al, ( 2008 ) stated that Hereditary spherocytosis is most normally seen in people of northern European and North America with prevelance of 1:2000 and less common in Afro-american and the sou’-east.

Pyruvate kinase lack

Pyruvate kinase lack ( PKD ) is one of chief 2nd seen enzymatic defects of the RBCs following G6PD lack due to mutant on the PLKR cistron that is located in chromosome 1, or due to protein instability. This upset is clinically known as a haemolytic anaemia sometimes as a consequence of status. Zanella and collegues stated that PKD has a prevelance of 1:20.

000 in the general white population as the cistron frequence surveies showed and is transmitted in an autosomal-recessive mode. With familial haemolytic anaemia, more than one cistron that controls the production of RBCs becomes faulty. PK is a really of import enzyme for the output of pyruvate and ATP molecules by glycolysis which provides red blood cell with oxidant defense mechanism and regulates the carrying of O2. A defect in the PK activity can do a lessening in the figure of these molecules which are needed for the ruddy blood cells function and endurances. Some patients who are affected with PKD develop no symptoms. However, in some other serious instances, this upset can do angina, cardiorespiratory decompensation or decease.

Sickle cell anaemiaSickle cell anaemia is inherited an autosomal recessionary upset ensuing from a defect in the haemoglobin I?-gene ( HBB ) nowadays in the short arm of chromosome 11 ( 11p15.5 ) ensuing the RBCs to decease before their expected lifetime and non replaced with normal cells fast plenty.Hemoglobin is responsible for transporting O2 inside RBCs and gives them their ruddy colour.

Normal hemoglobin becomes defected due to the replacing of the amino acerb glutamine in place 6 with valine, bring forthing haemoglobin reaping hook ( HbS ) . When HbS polymerize, Sickle cell anaemia is developed. The map of normal haemoglobin molecule is to pick up every bit much O2 from lungs and go oxygenated in red blood cells and give it off to tissues when RBCs acquire to the peripheral sites. However, in the instance of reaping hook haemoglobin, the molecules form a long concatenation similar construction as they tend to keep together. Therefore, the form of RBCs alters organizing reaping hook like form. The alteration of the construction may destruct the transit of the cells through the capillaries doing them to constellate in one topographic point barricading the blood vass taking to other complications excessively.Millions of people are affected by reaping hook cell worldwide.

However people from African America are the most vulnerable to disease with prevalence of 1 in 500 births.


Thalassemia is another type of familial blood upset which is inherited from parents due to a mutant in I± or I? cistron in the haemoglobin protein. Thalassemia can be divided into two different types harmonizing to the defected cistron. It can be either alpha-thalassemia where I± hematohiston cistron is altered or to the full absent, or beta-thalassemia in which the production of I? hematohiston cistron is hampered.Thalassemia conditions can impact the figure of RBCs from the bone marrow and their function. Therefore people with this upset usually demo a smaller size and a reduced degree of red blood cells in their blood stream compared to healthy individual. This can do harm to the variety meats and tissues in the organic structure as they are non acquiring adequate O.

Thalassemia upsets are found most frequently among people of Middle Eastern, Italian, Greek, Asian, and African descent. Many instances are diagnosed in early childhood and remain as womb-to-tomb status. Treatments for thalassaemias have seen a great betterment in recent old ages. Complications from thalassaemia are nor uncommon and their interventions are more frequent.

Comparison and contrast of Pyruvate kinase lack and reaping hook cell disease


The pyruvate kinase lack and reaping hook cell disease have a common point where both are ensuing of a defect in ruddy blood cell and doing anaemia. Pyruvate lack occurs when the protein pyruvate kinase is lacking in the ruddy blood cell due to the devastation of haemoglobin. Therefore impacting the endurance of RBCs.

whereas sickle cell happens when the haemoglobin in the RBCs become mutated and take the form of reaping hook “ C ” doing an obstructor to the map of the cells. Both Pyruvate kinase deficieny and reaping hook cell upsets are familial conditions that are passed on from parents to the kid.In pyruvate kinase lack the organic structure attacks the ruddy blood cells where the haemoglobin is destroyed, whereas in sickle disease the haemoglobin is formed faulty.

Both instances occur when there is mutant in the haemoglobin cistrons. There are besides similarities in the symptoms of both diseases like weariness and icterus. Peoples enduring from pyruvate lack besides suffer from anaemia like reaping hook cell disease. Severe anemia need blood transfusion in both instances. However, this can do the septic single really sick and fragile. Since PKD lead to the dislocation of RBCs and reaping hook cell alter the form of the ruddy molecules as a consequence of haemoglobin defect, a reduced degree of haemoglobin is seen.

In reaping hook cell disease the blood cells cluster together and close the blood vass as cells does non travel easy along the blood vass. They become stiff and gluey and form bunchs and tend to acquire stuck in the blood vass. While in pyruvate kinase lack the RBCs are left with really low energy due to the reduced figure in bring forthing ATP molecules.

Therefore, they get interrupting down more rapidly and non plenty new cells replacing them. This comparing in the biochemical procedures shows that each upset has its clinical consequence on RBCs.These two blood upsets may take to other serious complications.

For illustration, a individual affected with pyruvate kinase lack may develop cardiovascular disease ; nevertheless, instances of decease are low. Unlike a individual with reaping hook cell anemia it can do harm to variety meats of the organic structure and it can turn out fatal. Bloom ( 1995:25 ) provinces that “ The big proportion of reaping hook cell disease instances occur among black, both in Africa and in states with slave-trading history ” . But pyruvate lack is seen in all races, worldwide.


The diseases occur due to ruddy blood cell defect, have assorted grounds. Some are familial and some are acquired.

But largely, the defects in the protein of RBCs are due to familial factor and can enormously impact the wellness of a individual. Some surveies have stated that these syndromes are important familial heterogeneousness ” . Lots of interventions are now available for most of the disease and people can populate healthily one time brush with diseases. Blood is the life of human being and any lack in blood can be a really unsafe for life.Bone marrow organ transplant is available for patients who are diagnosed with familial blood upsets that do non hold an HLA-matched sibling giver.

The survey intervention program makes usage of new graft intervention program that aims in take downing toxicities and complications associated with the normal intervention programs. The blood root cells will be obtained from either non related giver or unrelated umbilical cord blood. So medical field is turning and this is decidedly a positive mark for patients of ruddy blood cell diseases.