Glycogen Metabolism in Health and Disease
Mutations occur in our daily lives in many forms from all and all organisms. “Mutations are changes in the genetic sequence, and they are a main cause of diversity among organisms” (Loewe, 1). Mutations occur at various levels and have been associated with different consequences. Some genetic mutations cause beneficial gains, while others cause harm. Sometimes the genetic coding that makes most of the molecular structures in our bodies can be altered. Most of the enzymes in our bodies are made of genetic codes, and they sometimes experience mutations. Among these enzymes are the Isoenzymes, which are a crucial factor in meeting the different tissues’ metabolic necessities, e.g., liver, brain, and muscles. These enzymes effect their work by controlling their development and various metabolic activities.
Also known as Isozymes, these particular enzymes are combinations of multiples of enzymes and differ in the mode amino acid sequencing but will perform the work of catalyzing a similar chemical reaction. The presence of the Isozymes allows the refining of metabolic activities to meet specific necessities of a definite tissue or developmental phase. “In the human body, glycogen is a branched polymer of glucose stored mainly in the liver and the skeletal muscle that supplies glucose to the bloodstream during fasting periods and to the muscle cells during muscle contraction” (Andany, 2016).
Table 1: Glycogen storage diseases.
The major transporter of glucose into the brain is GLUT 1 and acts as the arbitrator of glucose in the endothelium. It acts as a barrier to blood and brain. If the enzyme is altered through mutations, its works are blocked, and the GLUT 1 deficiency is developed. No glucose is transported in the brain. In this case, the implication of glucose deficiency in the brain, such as seizures, assimilated microcephaly, inability to move, and intellectual weakening, begin to manifest. These manifestations occur as just mild symptoms but accelerate to severe illnesses that will kill if remained unchecked.
In the muscles, the human skeletal muscles, two transporter enzymes work hand-in-hand to help uptake and transport glucose. They are the GLUT 1, and the GLUT 4.GLUT one is situated in the plasma wall and transports glucose to the muscle fibers. The other enzymes dwell in the intracellular storage vesicles, and it is usually transferred to the plasma membrane when stimulated through muscle contractions or insulin intake. If the proteins get altered through genetic mutations, there will be abridged glycogen deposited in the skeletal physiques or muscles. This usually happens after exercising hence permitting carbohydrates to be deposited in the muscles as glycogen. This prevents glucose synthesis in the body, thus directed to the de novo synthesis of body lipids. In due time, the fats will over accumulate and start causing insulin resistance. This increase in glucose in the skeletal muscles will cause the person to have type 2 diabetes.
In the liver and the pancreases, the glucose uptake and regulation is performed by the enzymes GLUT 2. This transporter will allow the entrance of glucose down the meditation gradient amid the blood and the tissue. If the enzymes become altered due to genetic mutations, they will not balance the concentrations between blood sugar and glycogen in the muscles. Fanconi-Bickel disease is then developed. “The Fanconi-Bickel disease is an autosomal recessive disorder caused by mutations in the GLUT2 gene and characterized by impaired utilization of glucose and galactose that leads to hypergalactosemia and hyperglycemia in the postprandial period and ketotic hypoglycemia in the fasting state.” (Adeva, 2016).
Several metabolites, as well as other cellular components, have been known and also predicted to cause clinical symptoms if they accumulate or get depleted in the body.
Table 2: diseases caused by accumulation or depletion of metabolites
Most of these metabolites are very useful in our bodies but only in the right amounts. “Research in metabolism has been propelled by the realization that metabolic perturbations accompany common human diseases” (DeBerardinis, 2012). Among the most known diseases caused by metabolites are PKU or phenylketonuria. It effects from genetic insufficiencies in phenylalanine (Phe) oxidation and the buildup of lethal Phe- associated metabolites that damage the intellectual growth. In some studies, a large variety of body metabolites have been found to cause clinical symptoms that cause serious diseases. These metabolites include the following; acylcarnitines, prostaglandins, amino acids, glycerophospholipids, and sphingo. Suppose glycogen is released in large amounts, and the body fails to release insulin to break it down. In that case, its aggregation will lead to the development of high blood sugar levels in the body, a condition known as diabetes.
“The failure to generate glucose from either of these two pathways results in a large flux into other pathways supplied by glucose-6-phosphate in the liver, including glycolysis, lipid synthesis, and nucleotide metabolism” (DeBerardinis, 2012). Suppose there will be massive buildups of glycogen and fats in the human liver. In that case, a patient will develop severe elevations of lactic acid, high amounts of uric acid, and many lipids in their bloodstreams. The rise of such components in the blood causes several diseases that need to be regulated using artificial metabolites or clinical procedures.
References
DeBerardinis, Ralph J, and Craig B Thompson. “Cellular metabolism and disease: what do metabolic outliers teach us?.” Cell vol. 148,6 (2012): 1132-44. doi:10.1016/j.cell.2012.02.032
Adeva, María & González-Lucán, Manuel & Donapetry-García, Cristóbal & Fernández, Carlos & Rodríguez, Eva. (2016). Glycogen metabolism in humans. BBA Clinical. 5. 10.1016/j.bbacli.2016.02.001.
Adeva-Andany, María M et al. “Glycogen metabolism in humans.” BBA clinical vol. 5 85-100. 27 Feb. 2016, doi:10.1016/j.bbacli.2016.02.001
Loewe, L. (2008) Genetic mutation. Nature Education 1(1):113