Sickle cell hemoglobin is a disease-causing substance with an amino acid change. This change results in the red blood cells preferentially interacting with other hemoglobin molecules. This change in amino acid preference is known as hydrophobic, and the effect is caused by the different residues of certain amino acids. The mutated amino acid b 6 Valine is a prime example. It is the mutated amino acid that is responsible for the disease-causing mutation.
Symptoms
The substitution of valine for glutamine alters the way that hemoglobin absorbs glucose in the blood. Because valine is more hydrophobic than glutamine, it can increase the proportion of irreversible glycation in sickle cells’ red blood cells. This increased irreversible glycation can interfere with the transport of oxygen and lead to a variety of symptoms, such as anaemia.
A point mutation in hemoglobin (HgbS) causes this anemia. When the amino acid glutamine is substituted with valine, the hemoglobin becomes less soluble under decreasing oxygen concentrations. As a result, sickle cells are composed of long chains that resemble spikes and are fragile. However, this type of sickle cell disease only manifests its symptoms when deprived of oxygen.
In addition, it increases the tendency of sickle cells to clump. This makes the cell more rigid and unable to squeeze through blood vessels. In severe cases, this condition may cause organ failure and damage. There is no known cure for sickle cell disease, but the symptoms associated with this condition are often life-threatening. When the cells become inflexible, they can clog up the arteries that supply oxygen to the rest of the body.
Causes
A point mutation in the gene encoding b-globin changes the amino acid glutamate to valine, forming a sickle-cell anemia. Valine replaces glutamate in position 6 of the beta chain, creating a hydrophobic patch. Hemoglobin deoxygenation causes this hydrophobic patch to form. It causes hemoglobin to resemble sickled red blood cells.
The substitution of valine for glutamate alters the glycation-dependent hemoglobin process. The hydrophobic properties of valine and the hydrophilic properties of glutamate change the way that hemoglobin uses glucose. Increased glucose availability increases ATP-ATPase activity, a major cause of sickle cell disease. This effect has been the subject of numerous studies.
The replacement of valine with glutamic acid impairs protein function. As the amino acids in proteins are positively and negatively charged, their interactions are critical to protein function. Because valine has a negative charge, it cannot bind to positively charged amino acids, a major problem with protein function results. This condition is known as sickle cell anemia. This condition is very dangerous, requiring immediate treatment.
Treatment
People with sickle cell disease have a mutation in the gene that causes their hemoglobin to be shaped like a sickle. Rather than carrying oxygen in the red blood cells, sickle cells contain valine in place of glutamate. Because these sickled cells are abnormal, they clump together in the blood, creating the characteristic reddish-orange sickles. This clotting process is inherited and occurs in about one percent of the population.
There are two approved medications for the treatment of sickle cell anemia. One, hydroxyurea, has been around for decades. The other, l-glutamine, was only recently approved by the FDA. Both have many questions, and very few published studies have been conducted. This makes it impossible to recommend a specific medication without further testing. But it is possible to reduce your risks with an alternative therapy.
Exclusion criteria
The phenotype of sickle cell disease (SCD) is caused by a substitution of glutamine for the amino acid valine at the 6th position in the b-chain of hemoglobin. The resulting protein is known as sickle hemoglobin (HbS). Patients with SCD are homozygous or heterozygous, and have either sickle cell trait or sickle cell anemia.
The efficacy of L-glutamine in treating sickle cell disease has not been proven. Most trials have only included patients with sickle ss0-thalassemia. The efficacy of HU is still unclear in the other sickling genotypes. This knowledge gap limits the development of treatments for the adult sickle cell population. Including all sickling disorders in late stage trials would solve this major problem, but it would require careful attention to inclusion/exclusion criteria, including safety assessments. The inclusion/exclusion criteria would vary among genotypes, and baseline hematologic and metabolic parameters will differ.
The design of new therapies to treat sickle vaso-occlusion presents numerous challenges, but advances in basic science have greatly expanded our knowledge of the disease. The most successful therapeutic agents have impacted sickle polymer formation directly. Although the development of novel drugs has been made in the last 30 years, there is still no specific treatment for SCD. The clinical trials of existing therapies are not effective.
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