Biochemical Implication in Metabolic Disorder
Enzymes refer to protein molecules that are essential in metabolic reaction due to their catalytic role. Enzymes are involved in almost every reaction that occurs in the body. Various enzymes exist and are differentiated in diverse ways. For instance, various enzymes are differentiated,for various substrates and locations (Weiss & Landfester, 2013). Enzymes achieve their catalytic role due to the presence of special features. According to Hammes (1982), one of the special features of enzymes is the ability to undergo conformational changes. This ability helps enzymes to catalyze reactions at possible maximum rates. Another special feature of enzymes is the entropy advantage. Enzymes comprise several functional groups that allow for the occurrence of intermolecular catalysis. Moreover, the binding of a substrate to an enzyme results in the formation of a single molecule that allows for a configuration that enables optimal rates of reaction.
| Substrate |
| Substrate |
| Enzyme and the Substrates |
| Enzyme |
| Products |
Fig 1: Lock and Key Model
| Energy |
| Products |
| Reactants |
| Without an enzyme |
| With an Enzyme |
| Activation energies in either case |
| Reaction Direction |
| Energy Released |
Fig 2: Enzyme and Activation Energy
Fructose metabolism involves several reactions in the liver. The ,first two steps of the reaction involve phosphorylation of fructose and cleavage of the resulting product (Caballero, Allen & Prentice, 2005). In the first reaction, fructose is phosphorylated to form fructose-1-phosphate. This reaction requires the presence of fructokinase enzyme. The second reaction involves fructose-1-phosphate cleavage (Harvey & Ferrier, 2011). This reaction is catalyzed by aldolase B enzyme. The products of this reaction include glyceraldehydes and dihydroxyacetone (DHAP).
Hereditary Fructose Intolerance (HFI) is an autosomal genetic condition that results in lack of production of aldolase B enzyme in the body. Aldolase deficiency results in the accumulation of fructose-1-phosphate. HFI is associated with several conditions such as liver failure and hypoglycemia. Caballero, Allen and Prentice (2005) explain that hypoglycemia occurs due to high level of fructose-1-phosphate that acts as inhibitors of phosphorylase enzyme. This enzyme is responsible for the conversion of glycogen to glucose. Consequently, glucose concentration in the body declines.
Several diseases are associated with mitochondria. These diseases may result due to abnormalities of the mitochondria or nuclear DNA whose transcription products are essential to mitochondria composition (Kleinman, 2008). The cori cycle is responsible for the conversion of glucose to lactate by an active muscle cell with the release of 2 ATP in the muscle cells while 6 ATP molecules are used in the liver. Therefore, if the cycle occurred in single muscle cell, the amount of ATP in cells would decrease. This decrease .is because the amount of ATP generated is less compared to that consumed and consequently altering cell metabolism.
| 1 Glucose Molecule |
| 2 Pyruvate Molecules |
| Glycolysis |
| Acetyl CoA |
| Citric Acid Cycle |
| ATP for cells |
| Cell metabolic Precursors |
| Coenzyme A |
| CoA
NAD+ |
| NADH + H+
CO2
|
Fig 3: Interaction of CAC with other cell metabolism processes
Fig 3: The TCA cycle
In producing ATP, as indicated in Figure 3, CAC links with the electron transport chain (ETC) to convert its products, NADH and FADH2, into ATP. NADH and FADH2 form the linkage of CAC and ETC as summarized in the figure below.
Fig 4: Linkage of CAC and ETC through NADH and FADH2
A defect in α-Ketoglutarate Dehydrogenase in the citric acid cycle would result in failure to convert α-Ketoglutarate to succinyl CoA. This defect will not affect the entire ccylce as other reaction will still occur. The process will be terminated after formation of α-Ketoglutarate. However, subsequent reactions will occur. This occurrence is because they are all reversible and hence the existence of an equilibrium will ensure a backward reaction to form succinyl-CoA (Harvey & Ferrier, 2011). Such reaction will cause an increase in the products citrate, isocitrate and α-Ketoglutarate. Other products will tend to decline. Failure of the process to undergo to completion will yield less FADH2 and NADH that are essential in ATP production.
Proton gradient in aerobic metabolism is attained through reactions of oxidation. FADH and NADH are used to generate electrons through oxidation and reduction reactions (Harvey & Ferrier, 2011). The electrons released are pumped into the intermembranous space of the mitochondria. Consequently, there is creation of a gradient potential across the inner membrane of the mitochondria as the number of electrons in the intermebraneous space increases. The electron gradient provides the driving force for phosphorylation and hence production of ATP. The electron gradient provides a proton motive force that is used to drive reaction of ADP and Pi to produce ATP (Alberts et al., 2002). This process involves coupling of oxidative and phosphorylation reactions. During oxidation of NADH, oxygen plays a crucial role in accepting the electrons release. Upon reduction, molecular oxygen is reduced to water.
References
Alberts, B., Johnson, A., Lewis, J., Walter, P., Raff, M., & Roberts, K. (2002). Molecular Biology of the Cell 4th Edition: International Student Edition.
Caballero, B., Allen, L. H., & Prentice, A. (2005). Encyclopedia of human nutrition. Amsterdam: Elsevier/Academic Press.
Hammes, G. (1982). Enzyme Catalysis and Regulation. Oxford: Elsevier Science.
Harvey, R. A., & Ferrier, D. R. (2011). Lippincott’s illustrated reviews, biochemistry. Philadelphia: Wolters Kluwer Health.
Kleinman, R. E. (2008). Walker’s pediatric gastrointestinal disease: Physiology, diagnosis, management. Hamilton, Ont: Decker.
Weiss, C. K., & Landfester, K. (2013). Enzymatic Catalysis at Interfaces—Heterophase Systems as Substrates for Enzymatic Action. Catalysts, 3(2), 401-417.
