Student ID: 000458585
June 5, 2015
Enzymes are special proteins that carry out chemical reactions, also known as catalysts. Two important features that make all enzymes catalysts are their ability to bind to a substrate. A substrate is anything that needs to be changed into something else. The second important feature is that it works to lower the activation energy without being used or changed in the reaction (Hudon-Miller, 2012. The breakdown of fructose in the liver starts off with two steps unique to fructose itself, prior to entering glycolysis. Fructose, a substrate, is broken down into the product, fructose-1-phophate, by the enzyme, fructokinase. The second step in the breakdown of glucose is when the product, fructose-1-phosphate is converted by the enzyme, aldolase B, into the two products, DHAP and glyceraldehyde. These two products are now capable of entering the glycolysis pathway (Hudon-Miller, 2012).
During fructose metabolism, fructose is transported into the liver cell and phosphorylated into fructokinase using ATP, which adds a phosphate to the substrate. Fructose-1-phosphate, or F-1-P, is the specific substrate acted on by the enzyme, aldolase B. Aldolase B takes F-1-P and makes the products, DHAP and Glyceraldehyde. These products are immediates in glycolysis to make fatty acids or ATP or it can go through gluconeogenesis to make glycogen (Sanders, 2013). Hereditary fructose intolerance, or HFI, is when there is deficiency in the enzyme, aldolase B. Aldolase B, can no longer take its substrate, F-1-P, and turn it into the products, DHAP and Glyceraldehyde. During HFI, fructose is still being phosphorylated by fructokinase, leading to a build up of F-1-P, and will no longer being used for glycolysis or gluconeogenesis. The continued use of phosphorous leads to the depletion of the free phosphate pool in the cells. The electron transport chain requires phosphate to make ATP. With the low amounts of free phosphate available, ATP production slows. Essentially, fructose is no longer being used as energy by the liver cells. Liver cells are now low on energy leading to liver damage and eventually liver failure. Fructose-1-phosphate produces the symptoms of HFI. It normally acts a signal in high blood sugar instructing the glucokinase to stay in the cytoplasm, so it does not go into the nucleus. When blood sugar is low, and F-1-P builds up, it signals the glucokinse to stay in the cytoplasm leading to a glycogenolysis and gluconeogenesis slowing down. When low blood sugar occurs, the liver cannot release glucose into the blood to help stabilize it, this is known as hypoglycemia. Many symptoms that are involved with hereditary fructose intolerance have to do with hypoglycemia, such as shakiness, headaches, and irritability, in addition to phosphate related liver issues (Sanders, 2013). Hypothetically, if the Cori cycle were to occur and remain within a single muscle cell there would be two ATP molecules produced by turning glucose into lactate and six ATP molecules to turn lactate back into glucose with a net loss of four ATP per cycle. If the glucose were resynthesized at the cost of ATP and GTP hydrolysis, it would form a futile cycle, until cell death (Concepts in Biochemistry, n.d.).
The citric acid cycle acts as a factory line of workers, each having a specific role. If there was a hypothetical defect or break in the cycle, and citrate synthase, for example, was not working, the cycles product, citrate, and the side-product, CoA, would not be made. If citrate is not made, the next enzyme, aconitase, would be unable to do its job and the next enzyme cannot do its job, and the Citric Acid cycle would not continue. If CoA isn’t made, then another Acetyl-CoA cannot also be made. Due to this defect, the citric acid cycle stops and is unable to produce the appropriate amounts of GTP,...
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