Hereditary fructose intolerance Essay Example for Free

Hereditary fructose intolerance Essay Enzymes are proteins that increase the rate of chemical activity. Their three dimensional structure determines their function, and is made of chains of amino acids that have folded into a specific shape with a unique property. Enzymes lower the activation energy needed for a chemical reaction, therefore speeding up the process. Multiple enzymes work together in metabolic pathways, taking a product (end result) of one metabolic reaction as a substrate (substance or molecule at start of process) for another reaction. Metabolic pathways create the avenue for fructolysis, the breakdown (catabolism) of fructose, occurring in the liver, and in muscle and fat tissue. Most of fructose obtained by diet is metabolized in the liver, where the enzyme fructokinase is abundant. This enzyme phosphorylates the substrate (fructose) into fructose-1-phosphate, which is then split into glyceraldehyde and dihydroxyacetone phosphate, both three carbon molecules that can enter the glycolytic pathway for further oxidation and energy production. Enzymes are specific to a substrate, meaning they have an active spot on the enzyme that will only work with a specific shape of a particular substance (substrate). Aldolase B deficiency Aldolase B is an enzyme found predominantly in the liver that plays a major role in fructose metabolism. In hereditary fructose intolerance (HFI), individuals have a build up of fructose 1- phosphate (F1P), due to the absence or deficiency of aldolaseB, necessary to break down F1P into the two three carbon molecules utilized in the glycolytic pathway. The F1P is toxic to cells and tissues in the body, causing phosphate to become unusable, and depleting phosphate storage and energy. The decreasing phosphate levels cause glycogenolysis in the liver to halt, affecting blood sugar levels. Persons with HFI can exhibit symptoms of vomiting, trembling, nausea, lethargy, hypoglycemia, hepatomegaly (enlarged liver), and jaundice after consuming foods containing fructose. These persons must avoid fructose to avoid the build up of F1P in their body, having a deficiency in aldolase B needed to metabolize the F1P. Fructose 1-phosphate Fructose is a monosaccharide, and has the same chemical formula as glucose, but a different structure. Fructose, a simple sugar found in honey, fruits, or even table sugar, is phosphoylated in the liver by the enzyme fructokinase, or in cells by enzyme hexokinase, to form fructose 1-phospahate. Adenosine triphosphate (ATP) supplies the phosphate group for both reactions. Aldolase B further breaks down the product (F1P) of fructolysis, (similar to glycolosis, just with fructose, instead of glucose) into two trioses. Role of aldolase B in breakdown of fructose Aldolase B is located mainly in liver of body and ensures second part of fructose metabolism is carried out. Aldolase B breaks down fructose-1-phosphate into two trioses, glyceraldehyde and dihydroxyacetone phosphate (USNLM, 2012). Both of these three-carbon molecules are needed for further enzymatic processes in our bodies. Case 2- Mitochondrial disease Mitochondrial disease is a complex failure of mitochondrial functions. Mitochondria supply most of the energy utilized in the body, and when not functioning properly, decreased energy production cause system failure that create cell injury and cell death. The person with this affliction faces serious health concerns, as there is no cure for mitochondrial disease, only symptom management. Cori cycle The Cori cycle occurs in liver cells, cells lacking mitochondria, and is important part in anaerobic glycolysis. Pyruvate, a product of glycolysis, is converted to lactate through anaerobic respiration. Anaerobic glycolysis produces lactate from breaking down glycogen in muscles. The lactate produced in skeletal muscle by anaerobic glycolysis is transported to liver after being released into bloodstream, for conversion to glucose. Then glucose is returned to muscle in blood for energy and glycogen replenishment (King, 2012). Glucose being consumed and resynthesized at the expense of ATP and GTP hydrolysis is termed by scientists as a â€Å"futile cycle† because it takes more energy (ATP) than is produced, with a net loss of 4 ATP (Wiley, 2012). This indicates that if the conversion of lactate to glucose occurred in same cell, the energy reserves of the cell would be depleted, because the 2 ATP produced by glycolysis would be offset by the 6 ATP needed for a gluconeogenesis, to convert lactate into glucose for muscle replenishment. This continued cycle would cause an energy deficit, as the muscles glycogen stores are minimal, so the energy reserves would be depleted rapidly. Citric acid cycle During step 5 of the citric acid cycle (Krebs cycle), a phosphate is bonded to the succinyl complex, once containing coenzyme A. This phosphate is then transferred to a GDP molecule, to be converted into a GTP molecule. This GTP molecule will give a phosphate to ADP to make an ATP for energy. A defect in this step would prevent an increased conversion of ADP to ATP when energy needs rise. Initially, acetyl CoA combines with oxaloacetate to make a citrate molecule. The citrate is isomerized to form isocitrate, which then is oxidized by NAD. This creates an unstable molecule that releases a CO2 molecule, creating alpha-ketoglutarate. Now, the acetyl CoA that was released in first step returns to oxidize the alpha-ketoglutarate and initiate conversion to succinyl-coenzyme A complex. A free H2O donates its hydrogen to the coenzyme A, and a free phosphate comes in to replace the coenzyme A. This newly bonded phosphate will be transferred to GDP molecule as indicated previously, for conver sion to GTP, then ADP, and finally ATP for energy. Coenzyme Q10 Coenzyme Q10 ( CoQ10) is found in cell membranes, and is critical in all cells in producing ATP (energy) for the body. CoQ10 carries electrons from enzyme complex I and II to complex III in mitochondria. This transfer of electrons in the electron transport chain (ETC) pushes hydrogen through the inner cell membrane to make a proton gradient needed by ATP synthase to make ATP (Wikipedia, 2012). CoQ10 is the lone molecule that does this task in ETC, and is vital to this function of ATP production in cells. References King, Michael W, PhD. (2012). Gluconeogenesis: Glucose synthesis. Retrieved from The Medical Biochemistry Page website: http://themedicalbiochemistrypage.org/gluconeogenesis.php U.S. National Library of Medicine. (2012). ALDOB. Retrieved from http://ghr.nlm.nih.gov/gene/ALDOB Wikipedia. (2012). Coenzyme Q10. Retrieved from http://en.wikipedia.org/wiki/Coenzyme_Q10 Wiley, John. (2012). Interactive Concepts in Biochemistry: The Cori Cycle. Retrieved from http://www.wiley.com/college/boyer/0470003790/animations/cori_cycle/cori_cycle.htm