Enzymes function like a lock and key. The substrate binds to the active site of the enzyme like a key into a lock. The enzyme breaks the bonds of the substrate and releases it without being consumed in the process. Substrates can also function as inhibitors, competing for the active site. (Wolfe, 2000). Sometimes one enzyme will work on one particular substrate, in other circumstances, such as with fructose, two or more enzymes work to break down a substrate so that it can be used by the body.
Fructose is first broken down into fructose 1 phosphate by the enzyme fructokinase.
Then fructose 1 phosphate is further broken down into dihydroxyacetone phosphate (DHAP) and glyceraldehyde by the enzyme aldolase b. (Hudon-Miller, 2012). At this point, DHAP and glyceraldehyde enter the glycolysis cycle where they can be further processed into ATP, the body’s main source of energy. Deficiency in aldolase b Aldolase b is the enzyme which breaks down fructose 1 phosphate into DHAP and glyceraldehyde.
Hereditary fructose intolerance (HFI) is an autosomal recessive disorder caused by a deficiency of aldolase b.
HFI causes fructose 1 phosphate to build up in the liver, kidneys, and small intestines. This build up is toxic and leads to death of organ tissues over time. Symptoms of HFI include severe abdominal pain, vomiting, hypoglycemia, and a dislike for sweets. (Coffee & Tolan, 2010). The breakdown of DHAP releases a phosphate group used in ATP synthesis. Because fructose 1 phosphate is not broken down into DHAP and glyceraldehyde, it does not enter the glycolysis pathway so the body misses out on the ATP that would have been created if it had gone on to glycolysis. Hudon-Miller, 2012). The death of liver cells and the reduced number of phosphate groups available for use by the body lead to hypoglycemia, liver dysfunction, and other problems associated with hereditary HFI. (Coffee & Tolan, 2010). Diagram of lock and key model (Wolfe, 2000) Diagram of activation energy See attachment Substrate, role of aldolase b The specific substrate acted on by aldolase b is fructose 1 phosphate. (Hudon-Miller, 2012). The role of aldolase b is to break down fructose 1 phosphate into DHAP and glyceraldehyde to enter glycolysis.
DHAP releases a phosphate group which is used in the production of ATP. Fructose is broken down into fructose 1 phosphate by fructokinase. Then, fructose 1 phosphate is broken down into DHAP and glyceraldehyde by aldolase b. (Hudon-Miller, 2012). Interconversions of Cori Cycle If the interconversions of the Cori Cycle occurred and remained within a single, glucose would be converted to pyruvate by glycolysis and then converted back to glucose by gluconeogenesis. This process is called a “futile cycle” and dissipates most of the cell’s energy reserves, ATP, in the form of heat.
A “futile cycle” is when two chemical reactions occur at the same time, in opposite directions, and have no effect other than to dissipate energy in the form of heat, without any useful metabolic work being done. (Somoilov, Plyasunov, & Arkin, 2005). Dynamic model of citric acid cycle (Wolfe, 2000) Defect preventing conversion of ADP to ATP A potential defect could occur anywhere in the citric acid cycle. If a defect did occur in the citric acid cycle, aerobic respiration would cease and ATP, the energy source for the body, would not be produced.
If a defect were to occur with isocitrate, NADH+H would not be able to enter the electron transport chain (ETC) and generate ATP. The enzyme alpha-ketoglutarate, which follows isocitrate, would not be able to generate NADH+H to go into the ETC and produce ATP. This would continue on throughout the citric acid cycle. (Illingworth, n. d. ). Role of coenzyme Q10 The Electron Transport Chain (ETC) is a chain of molecules which carries electrons from a high energy state to a low energy state. As the electrons move from one molecule to the next, energy is released.
The role of coenzyme Q10 is an electron carrier from enzyme complex I and enzyme complex II to enzyme complex III. Coenzyme Q10 is the only molecule which can perform this function. (Crane, 2001). As the electrons are transferred, hydrogen atoms are pumped across the inner mitochondrial membrane, to the inter-membrane space (between the inner and outer membrane). This creates a positive concentration of energy outside of the inner membrane and negative energy inside the matrix of the mitochondria.
The hydrogen atoms then move down the concentration gradient, through an enzyme complex called ATP synthase, back into the matrix of the mitochondria through a process called chemiosmosis. Then through a process called oxidative phosphorylation, the ATP synthase takes ADP and an inorganic phosphate and generates ATP. (Wolfe, 2000. ) References Coffee, E. & Tolan, D. (2010). Mutations in the promoter region of the aldolase b gene that Cause hereditary fructose intolerance. Journal of Inherited Metabolic Disease, 33 (6) 715-725. Crane, F. (2001). Biochemical functions of coenzyme Q10.
Journal of American College of Nutrition, 20 (6) 591-598. Hudon-Miller, S. (2012). Metabolism. Retrieved from http://www. bit. ly/grt_metabolism_nov Illingworth, J. (n. d. ). The citric acid cycle. Retrieved from http://www. bmb. leeds. ac. uk/ Illingworth/metabol/krebs. htm Somoilov, M. , Plyasunov, S. , & Arkin, A. (2005). Scholastic amplification and signaling in enzymatic futile cycles through noise-induced bistability with oscillations. Proceedings of the National Academy of Science of the United States of America, 102 (7) 2310-2315. Wolfe, G. (2000). Thinkwell Biochemistry. Retrieved from http://www. thinkwell. com