Conformational Disease From Biochemical †Myassignmenthelp.Com

Question: Discuss About The Conformational Disease From Biochemical? Answer: Introducation Phosphoglycerate kinase deficiency is an inherited metabolic disorder that rarely occurs in humans, marked by the deficiency of the enzyme phosphoglycerate kinase (PGK). It is a group of metabolic muscle diseases interfering with the carbohydrate metabolism within the body, and eventually the production of energy for normal body functioning. The enzyme is accountable for breaking down of glycogen molecule within the body. PGK is a valuable enzyme involved in the glycolytic pathway that carries out the catalysis of the conversion of 1,3-bisphosphoglycerate into psychology cerate and generation ATP. PGK is in competition with the enzyme diphosphoglycerate mutase (DPGM) for the substrate 1,3 DPG in the reaction. The alternative routing of glycolytic intermediates is known as the energy clutch of glycolysis. When glycolysis takes place, the simple sugar molecules are broken down to give rise to energy in the form of ATP. It is to be noted that the enzyme is ubiquitous as its expression is found in all tissues with the exception of testes. The deficiency is an inborn error that is inherited in an X-linked manner. The gene whose mutation leads to this deficiency is Xq13, present on the X chromosome. Different mutations have been identified though the factors for clinical manifestations are still unknown (1). Mutations taking place in the PGK1 gene leads to a reduction of the activity of phosphoglycerate kinase, thereby disrupting the production of energy. Th ultimate result is cell death or cell damage. There is little information on the reasons for this abnormality to preferentially impact brain cells in some people and red blood cells in others. Symptoms of this disorder include haemolytic anaemia that is lower levels of circulating red blood cells, the impaired condition of speech and writing, impaired condition of intellectual ability, pain and stiffness due to exercise, spleen enlargement and hemiplegia or paralysis of the body on one side (2). Research Present research on phosphoglycerate kinase deficiency is going on across the globe with a special focus on the invention of a better diagnosis method that would permit early-stage identification of at-risk individuals. Animal models are being developed that would help in understanding the disease in a better manner. Development of gene therapies and enzyme replacement therapies are also on the ist of objectives for further research (3). Diagnosis The three primary features of phosphoglycerate kinase deficiency are an intellectual disability, hemolytic anaemia and muscle problems. A person suffering from this disease might be affected by more than one of the mentioned characteristics; however, all the three signs are rare to be present in one individual. It is to be noted that most of the patients suffering this condition are affected to a moderate level. The disorder is completely expressed in males only while heterozygous females suffer from mild haemolytic anaemia with no signs of intellectual disability or myopathy. Myopathy along with muscle plain, cramps and stiffness are indicated in young male and adolescents. Myoglobinuria is seen in cases of severe episodes (4). The diagnosis is done based on physical examination, and laboratory results confirm the same. Biochemical studies involve an indication of low muscle PGK enzyme activity and low erythrocyte (below 25% and 23% respectively). The differential diagnosis must inc lude other causative factors for hereditary nonspherocytic hemolytic anaemia. Molecular prenatal diagnosis is usually done for an index case. Business of the disease is possible at birth if enzymatic testing is carried out. Treatment Treatment of PGK deficiency commonly takes into consideration iron supplements together with blood transfusions depending on the severity of the patient condition. A splenectomy is an option for patients who have enlargement of the spleen, and this method has been proved to be effective for some cases. It is very important that an individual avoids strenuous exercise when there is an indication of muscle breakdown and under such conditions, special care is required to be taken. The neurologic crisis demands complete rest so that life-threatening situations do not arise. When there is severe neurological deterioration, bone marrow transplant is an option (5). Genetic counselling has been indicated to show some benefits for the patients as well as their families. Other treatment options are supportive (6). Policy The Australian Research Council has constantly been supporting the research on different significant topics in relation to metabolism, which includes PGK deficiency. As per the Australian Research Council (ARC) Medical Research Policy funding is being allocated for future research. This funding is either directly or in collaboration with the National Health and Medical Research Council (NHMRC). The policy requires research to be done on aspects of therapeutic approaches and bioengineering, which are essential aspects of PGK deficiency research (7). References Tamai M, Kawano T, Saito R, Sakurai K, Saito Y, Yamada H et al. Phosphoglycerate kinase deficiency due to a novel mutation (c. 1180AG) manifesting as chronic hemolytic anemia in a Japanese boy. International Journal of Hematology. 2014;100(4):accounting. Chiarelli L, Morera S, Bianchi P, Fermo E, Zanella A, Galizzi A et al. Molecular Insights on Pathogenic Effects of Mutations Causing Phosphoglycerate Kinase Deficiency. PLoS ONE. 2012;7(2):e32065. Lopez-Manzaneda S, Torres R, Olivier E, Garcia-Torralba A, Sanchez-Dominguez R, Alberquilla O, Mountford J, Ramirez JC, Bueren JA, Segovia JC. Modelling pyruvate kinase deficiency in human progenitors using crispr/cas9. Haematologica 2017 Jun 26;102: 446-446. Pey AL, Maggi M, Valentini G. Insights into human phosphoglycerate kinase 1 deficiency as a conformational disease from biochemical, biophysical, and in vitro expression analyses. Journal of inherited metabolic disease. 2014 Nov 1;37(6):909-16. Garcia-Gomez M, Calabria A, Garcia-Bravo M, Benedicenti F, Kosinski P, Lpez-Manzaneda S, Hill C, del Mar Mau-Pereira M, Martn MA, Orman I, Vives-Corrons JL. Safe and efficient gene therapy for pyruvate kinase deficiency. Molecular Therapy. 2016 Jul 1;24(7):1187-98. Saudubray JM, Baumgartner MR, Walter J, editors. Inborn metabolic diseases: diagnosis and treatment. Management; 2016 Nov 10. ARC Medical Research Policy | Australian Research Council [Internet]. Arc.gov.au. 2017 [cited 16 September 2017]. Available from: https://www.arc.gov.au/arc-medical-research-policy