(Figure 2, http://en.wikipedia.org)
work together in specific orders and create metabolic pathways; this is how enzymes take on the product of other enzymes as substrates. In doing so, catalytic reactions occur and the products formed are then passed onto another enzyme. Enzymes work by lowering the activation energy for reactions; this speeds up the rate of the reaction process as illustrated in figure 3 below (Grisham, 2012). (Figure 3, http://4.bp.blogspot.com)
An example of how enzymes work within the body is the breakdown of fructose. Energy obtained from carbohydrates goes through a process called glycolysis. Glycolysis a series of biochemical reactions in which one glucose molecule is oxidized into two pyruvic acid molecules and a small amount of adenosine triphosphate (ATP). Generation of high energy molecules are used as cellular energy sources in aerobic and anaerobic respiration. The products formed through glycolysis usually enter into the citric acid cycle and the electron transport chain to produce more energy. Fructose enters the glycolytic pathway through the liver or skeletal muscle. For example, in the liver, fructose is phosphorylated by the enzyme fructokinase to fructose-1 phosphate. The six carbon fructose is split into three carbon molecules, glyceraldehyde and dihydroxyacetone phosphate. Glyceraldehyde is then phosphorylated by another enzyme so it can also enter into the glycolytic pathway (New world encyclopedia, 2008).
Hereditary fructose intolerance (HFI) is a disease that is caused from a mutation in the liver isozyme fructaldolase, also known as adolase B. Adolase B is found in the liver and is directly involved in the metabolism of fructose. Fructose from the diet is phosphorylated by fructonkinase to form fructose-1-phosphate, the specific substrate of adolase B. In individuals with HFI, who lack adolase B, fructose challenge leads to the accumulation of fructose-1-phosphate and thereby to the sequestrian of inorganic phosphate. In this environment, the activation of the liver phosphorylase (which is required for glucose formation) is prevented, and purine nucleotide breakdown is initiated.
Glucose formation is subsequently halted by inhibiting both gluconeogenesis and glycogenolysis, and fructokinase activity is eventually inhibited. Hypoglycemia, fructosemia, hyperuricemia, and acidosis result from the arrested metabolism (Cox, 2002, pg. 7-8). The ALDOB gene is responsible for making the adolase B enzyme. Mutations in the ALDOB gene cause HFI. This mutation changes the shape of adolase B, therefore it is difficult for the enzyme to form a tetramer, and if it cannot form a tetramer it cannot metabolize fructose (Genetics home reference, 2011).
Mitochondria create energy needed for the body to function properly. Mitochondrial disease results when there is a dysfunction in the way the mitochondria convert the energy of food molecules into ATP. When this dysfunction occurs, less energy is created for the body to use. This can lead to cell injury and cell death. Mitochondrial disease can cause loss of motor control, muscle weakness and pain, gastrointestinal disorders, swallowing difficulties, cardiac disease, liver dysfunction, lactic acidosis, and numerous other problems. (What is mitochondrial, n.d.).
The Cori cycle is also known as the lactic acid cycle. It is the metabolic pathway that produces lactate through anaerobic glycolysis in the muscles. Muscular activity requires energy that is provided by the breakdown of glycogen in different skeletal muscles. This breakdown is known as glycogenolysis which releases glucose-6-phosphate (G-6-P). G-6-P then enters into glycolysis and it provides ATP to the muscles to utilize as energy. ATP stores are constantly in need of replenishment during muscular activity. ATP is generated by the breakdown of glycogen. Glycolysis occurs under aerobic and anaerobic conditions (Ophardt, 2003).
Muscle cells are anaerobic, they convert glucose to lactate. The lactate goes back to the liver to convert back to glucose. The liver works under aerobic conditions. When glucose is converted back to lactate in the muscles, 2 ATP are formed. When the liver converts the lactate back to glucose, it loses 6 ATP and allows the muscle to form 2 ATP. If lactate stayed in the muscle cell and converted it back to glucose in the muscle cell, the muscle cell would not be able to generate enough ATP to survive since the muscle cell depends on the liver to help generate its ATP. The liver is able to generate its own ATP because of its aerobic condition, but the muscle cannot because of its anaerobic condition.(Figure 5, Citric Acid Cycle) (Figure 6, Citric Acid Cycle Aerobic Metabolism)
The citric acid cycle is the gateway to aerobic metabolism (figure 6) of molecules to form an acetyl group or a dicarboxylic acid. It provides the majority of energy used by aerobic cells. It takes place in the mitochondrial matrix of cells. Simply put, glucose and oxygen combine together and form carbon dioxide, water and ATP. The water and carbon dioxide are merely the waste products of the reaction. The first and final products of the citric acid cycle are citric acid. The citric acid breaks down and regenerates during the process of ATP synthesis. To look a little deeper at the citric acid cycle see figure 5 above. Figure 5 illustrates how Acetyl CoA combines with oxaloacetate to make citric acid.
When the citric acid loses carbon dioxide from the oxaloacetate, the electrons then transfer to coenzyme nicotinamide adenine dinucleotide (NAD+) to make NADH. Acetyl CoA will produce 3 NADH. NADH transfers electrons to other atoms like glutamine to form QH2. The regeneration of the oxaloacetate in the last stage combines again with Acetyl CoA and the cycle continues allowing the cells to produce more ATP. In the citric acid cycle there is only one chemical reaction that produces ATP. The reaction that indirectly produces ATP is the hydrolysis of succinyl coenzyme A (CoA). If there were a defect with the enzyme succinyl CoA, GTP would not be formed to couple with adenosine diphosphate (ADP) to make ATP (Berg, Tymoczko & Stryer, 2002).
Coenzyme Q10 is an oil soluble substance found mostly in the mitochondria of cells. It is a part of the electron transport chain, aids in aerobic cellular respiration which generates ATP for energy. In the inner mitochondrial membrane, electrons from NADH and succinate pass through the electron transport chain (ETC) to the oxygen which is reduced to water. The transfer of electrons through the ETC results in the pumping of hydrogen across the membrane creating a proton gradient across the membrane, which is used by ATP synthase to generate ATP. Coenzyme Q10 functions as an electron carrier from enzyme complex 1 to complex 2 to complex 3 in this process. This is crucial in the process, since no other molecule can perform this function. Thus, Coenzyme Q10 functions in every cell of the body to synthesize energy (Wikipedia, 2011, pg. 3).
In conclusion, enzymes play a vital role in metabolic functioning. A defect in adolase B can cause detrimental effects within the body causing an accumulation in fructose because it is unable to be metabolized. On the same note, if mitochondria are not functioning properly, there are also many complications that can occur due to energy production, use, storage, and exchange dysfunctions.
Berg , J., Tymoczko , J., & Stryer , L. (2002). The citric acid cycle. W H Freeman. Retrievedfrom http://www.ncbi.nlm.nih.gov/books/NBK21163/ Cox, T. M. (2002). The genetic consequences of our sweet tooth. Nature Reviews Genetics, 3, 7-8.
Genetics Home Reference. (2011, June). Genetics home reference. Retrieved fromhttp://ghr.nlm.nih.gov/gene/ALDOB Grisham, C. M. (2012, March 19). Enzyme. Retrieved fromhttp://en.wikipedia.org/wiki/Enzyme New world encyclopedia. In (2008). New World Encyclopedia. Retrieved
fromhttp://www.newworldencyclopedia.org/entry/Fructose Ophardt, C. (2003). Cori cycle. Retrieved fromhttp://www.elmhurst.edu/~chm/vchembook/615coricycle.html Retrieved from http://4.bp.blogspot.com/_uzrWbt2ZlyE/TInsfGBK8I/AAAAAAAAAGQ/nuRopXPltaI/s1600/energy-level-diagram-activationenergy.jpg Retrieved from https://encrypted-tbn3.gstatic.com/images?q=tbn:ANd9GcQhdUVgbYF5K4R3arXmlygh5S2R8Uir179aaPOBa2Znl-9SS3Zkw) What is mitochondrial disease. (n.d.). Retrieved fromhttp://www.umdf.org/site/c.8KOJ0MvF7LUG References
Wikipedia Contributors. (2011, November 14). Coenzyme Q10. Retrieved fromhttp://en.wikipedia.org/wiki/Coenzyme_Q10