Carbohydrate Storage Disease
Carbohydratesrefer to sugars. Sugars can be either complex or simple. Sucrose isan example of a simple sugar that is made up of two simpler onesknown as fructose and glucose. Lactose is another type of sugar,which comprises of galactose and glucose. Enzymes break down bothlactose and glucose so that the body can easily absorb as well as usethem. Examples of carbohydrates include pasta, rice, and bread. If aprotein (enzyme) that is required to break down a particular sugar isdeficient, the sugar may accumulate and cause problems in the body.Key symptoms encompass tiredness, low blood sugar, and weakness.Since there are different proteins (enzymes), which are responsiblefor the breakdown and production of glycogen, there are numerousdisorders of carbohydrate storage as well. The purpose of this paperis to discuss two most prevalent carbohydrate storage illnesses,namely, type I and type II.
Carbohydratestorage diseases are categorized in accordance with an enzymemalfunction or deficiency as well as the body part that is affectedby the disorder. Carbohydrate storage illnesses mostly affect themuscles and the liver. Nonetheless, some disorders affect otherparts, for example, the heart, kidney, bowel, nervous system, andblood vessels.1Thus,the different types include type XI, 0, II, V, III, IV, VII, and IX.
BiochemicalMechanism Von Gieke’s Disease
VonGieke’s disease, also known as type I, is the most prevalent of thecarbohydrate storage diseases. It is categorized under GSD (glycogenstorage diseases). The glucose-6-phosphatase enzyme causes GSD I. Itimpairs the liver’s ability to breakdown glycogen into glucose.Additionally, it causes acute hypoglycemia, especially during fastingand leads to augmented glycogen levels in the kidneys and the liver.The mechanism whereby glucose is synthesized fromglucose-6-phosphatase entails a number of different steps. First,glucose-6-phosphatase has to be moved from the cytosol (place ofsynthesis) via gluconeogenesis to the lumen, which is found withinthe endoplasmic reticulum. Inside the endoplasmic reticulum, thephosphate removal occurs via ER-localized glucose 6-phosphate. Then,the glucose is moved back to cytosol along with the inorganicphosphate. Defects during the process of releasing glucose fromglucose-6-phosphatase cause increased cytosolic glucose 6-phosphatethat results into augmented glycogen levels and resulting excessivestorage.1,2
Description of Drugs
VonGierke’s disease has no cure, but it can be managed by treating keysymptoms of the illnesses. Some of the drug targets includeAllopurunol, Lipid-lowering Medications, and ACE inhibitors.
Allopurinol is a xanthine oxidase’s inhibitor, which is utilized toprevent increased uric acid within the bloodstream. In other words,it causes less uric acid synthesis. It is employed to inhibit goutafter dietary therapy does not entirely normalize the concentrationlevels of the uric acid. The drug acts on catabolism of purineswithout disrupting purine biosynthesis. It decreases uric acidproduction through inhibiting its biochemical reactions before itsformation.4
Lipid-loweringmedications include statins and fibrates, which are utilized to lowerthe levels of lipids, especially when there is good control ofmetabolism. Statins refer to a group of drugs that help reducelow-density lipoprotein cholesterol in the bloodstream. Fibratesdenote to a set of amphipathic carboxylic acids, which are utilizedto treat different metabolic disorders, especiallyhypercholesterolemia.4
ACE inhibitors are utilized to cure microalbuminuria, which is aninitial renal dysfunction indicator. ACE inhibitors preventAngiotensin II synthesis, which is an element that results in musclecontraction around blood vessels, thus narrowing them. Narrow bloodvessels cause hypertension. ACE inhibitors allow blood vessels todilate and reduce blood pressure. Reduced hypertension enables theheart to pump blood easily and enhance its functionality.Additionally, it reduces the kidney disease progression by slowingdiabetes and hypertension. 4
Biochemical Mechanism of Pompe’sDisease
Pompe’sdisease also known as typeIIis a disorder wherein GAA is absent or is insufficient. GAAdeficiency causes a gradual increase of lysosomes’ glycogen in bodytissues where skeletal and cardiac muscles are severely damaged.Researchers have identified three forms of Pompe disease that vary inseverity as well as at the age they develop. These types arenon-classic infantile-onset, classic infantile-onsite, and lateonset. Symptoms range from severe skeletal muscle and hypertrophiccardiomyopathy in babies to moderately weakened forms that occur as agradual myopathy that does not involve the cardiac muscles. Thedefect in lysosomal GAA affects lysosomal-modified glycogendegradation unlike the deficiencies in other GSDs, which affect thesynthesis of glycogen or energy production regulation.5
LysosomalGAA hydrolyzes both alpha-1, 6 and alpha-1, 4-glucose linkages foundin the lysosome’s low pH environment. As said before, the enzymeshortage causes glycogen buildup within the cytoplasm and lysosomes,leading to the destruction of tissues.6The effects may spread to vesicle systems, which are connected tolysosomes as well as may affect receptors, for example, glucosetransporter 4, which surround the organelles. Enzyme activity isrelated to genotype and is minimal or absent in individuals withinfantile-phenotype as well as variably decreased in those withlate-onset phenotype.7
AlglucosidaseAlfa is an enzyme, which treats infantile-onset Pompe disease. It isan enzyme replacement therapy drug. It contains acidalpha-glucosidase, a human enzyme, which is lacking in patients withPompe illness. Additionally, it aids with glycogen absorption anddigestion. The drug is available on doctor’s prescription. 8
Myozymeis a type of GAA. It comprises of an enzyme, which occurs naturallyin healthy people’s body. The enzyme may lack in some people due toa genetic illness. It aids in replacing the missing enzyme inindividuals without it. Myozyme is used to treat Pompe disorder inchildren and adults. It has shown to enhance ventilator-free survivalparticularly in individuals with Pompe disease’s infantile-onset. 8
Lumizymeis an ERT (enzyme replacement therapy). It offers an exogenous GAAsource, which is a crucial lysosomal enzyme, which is absent ordeficient in individuals suffering from Pompe disease, resulting inthe accumulation of intralysosomal glycogen. It is intended forpatients with late non-infantile onset Pompe illness.8
Conclusively, this essay has outlined different types of carbohydratestorage disorders. It has defined carbohydrate storage disorders asillnesses that are caused by an enzyme deficiency. The paper hasfurther discussed two carbohydrate storage illnesses namely, VonGierke’s disease and Pompe’s disease by looking into theirbiochemical mechanisms and drug targets. Both diseases have no cure,but they can be properly managed. Enzyme deficiency in Von Gierke’sillness makes the liver unable to break down glucose. Drug targetsfor type I include Allopurinol, lipid-lowering medications, and ACEinhibitors while those for Pompe encompass Alglucosidase Alfa,Myozyme, and Lumizyme intravenous. Other than use of drugs, themanagement of these illnesses requires proper nutritional management,exercises, and supportive therapies. Type I is easy to manage andsymptoms can be alleviated by reducing sugar intake.
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