Living organisms depend on biochemistry to power various chemical reaction cycles which are important for the overall biological functioning of an organism. Chemical reactions occur at a specific rate in certain conditions and require input energy (activation energy) to be supplied before a reaction can begin. Since a reaction cycle consist of many consecutive step, slowing one step slows down the whole cycle. Enzymes are proteins which act as catalysts in biochemical reactions and speeds up reactions to rates that are high enough for biological functioning. Enzymes manage this by providing an alternative reaction route with lower activation energy.
The breakdown of fructose is an example of an enzyme catalyzed reaction. Fructose is a monosaccharide sugar found in fruits and honey. In the body, it is used as a source of energy similar to glucose. The breakdown of fructose starts with the enzyme fructokinase produced in the liver which acts on fructose to produce fructose 1-phosphate. The second step is catalyzed by the enzyme aldolase B which splits fructose 1-phosphate into dihdroxyacetonephosphate (DHAP) and glyceraldehydes (Berg, Tymocz, & Stryer, 2002). The two products enter the regular glycolysis cycle and are metabolized in a manner similar to glucose.
Deficiency of aldolase B
Hereditary Fructose Intolerance (HFI) occurs in 1 in every 20,000 births and makes it impossible for the body to digest fructose due to lack of aldolase B enzyme (Esposito et al., 2002). This results from a gene mutation. For a person with HFI, fructose metabolism stops with the formation of fructose 1-phosphate which in large concentrations can hamper normal liver operations. Patients suffering from HFI need to avoid fructose in their diet.
Lock and key model of enzymatic activity
The lock and key model explains enzyme specificity where an enzyme acts on only one substrate. In this model an enzyme has an active site of a particular structure and it will catalyze only the substrates that fit in this active site. This is analogous to actual locks and keys in which only the key (substrate) with the right size and geometry that fits into the keyhole (active site) of the lock (enzyme). The figure below is a diagram of the lock and key model of enzyme function.
Diagram of effect of enzymes on activation energy
Reactants have higher free energy than products and biochemical reactions occur within the homeostasis constraints of living things to reduce free energy. However for the reaction to occur, it needs activation energy which brings reactants together and weakens chemical bonds allowing a reaction to proceed. Reactions with high activation energy are very slow. Enzymes are organic catalysts which speed up biochemical reactions by reducing the required activation energy. The diagram below shows the effect of a catalyst on activation energy.
Substrate acted on by aldolase B
Aldolase B enzyme is produced in the liver and catalyzes the reversible cleavage of fructose 1-phosphate into glyceraldehydes and DHAP.
The role of aldolase B in the breakdown of fructose
Fructose is an isomer of glucose and is used as an energy giving food. After absorption, fructose undergoes phospholation in the liver, catalyzed by fructokinase to give fructose 1-phosphate. This substrate undergoes a cleavage reaction catalyzed by aldolase B to give fructose 1-phosphate into glyceraldehydes and DHAP which then enter gyclolysis and are metabolized as regular carbohydrates. In the absence of aldolase B, fructose 1-phosphate accumulates in the liver and phosphates reserve for the formation of ATP is depleted.
Energy distribution in the Cori Cycle
In the Cori cycle (Lactic Acid cycle), lactate produced in the muscles through anaerobic glycolysis of glucose is transported by blood to the liver. In the liver, lactate is converted back to glucose and carried by blood to muscles. The anaerobic glycolysis in muscles releases 2 ATP of energy while conversion of lactate to glucose in the liver uses 6 ATP of energy (Berg, Tymocz, & Stryer, 2002). If this process was limited to a single cell, it would use more energy than it produces hence would not be suitable as a metabolism mechanism.
Role of Citric Acid Cycle in Aerobic Metabolism
Glycolysis releases a fraction of the energy found in glucose with the rest being released during aerobic metabolism of glucose in the citric acid cycle. The citric acid cycle is a common metabolism pathway for oxidation of fuel molecules such as amino acids, fatty acids and carbohydrates (Berg, Tymocz, & Stryer, 2002). Pyruvate from gylcolisis is oxidized to acetyl coenzyme which enters the citric acid cycle in the mitochondria. The citric acid cycle is important because it is a source of precursor chemicals for building blocks such as amino acids and storage materials cholesterol and porphyrin besides producing energy (Jason & Tischler, 2012). Besides acetates, the cycle consumes water and reduces nicotinamide adenine dinuckeotide (NAD+) to NADH and gives of carbon dioxide. The diagram below shows the role of citric acid cycle in aerobic metabolism
Enzyme defects
Enzyme defects affecting the citric acid cycle can prevent an increase in ATP production in response to higher demands. One such defect would be in the enzyme catalyzed reduction of NAD+ to NADH. This is because NAD+ is the main energy carrier in the cycle and the energy is released only when it is reduced to NADH. The enzymes responsible for generation of NADH in the citric acid cycle are Malate dehydrogenase, α-Ketoglutarate dehydrogenase and isocitrate dehydrogenase (Berg, Tymocz, & Stryer, 2002). Any defect in the genes that code for these enzymes would hamper the citric acid cycle reducing energy generated.
Role of Coenzyme Q10 in the synthesis of ATP as part of electron transport chain
Coenzyme Q10 (CoQ10) is a fat soluble ubiquinone that has a head made of a benzoquinone group and an isoprenyl tail (Crane, 2001). CoQ10 can exist in a completely oxidized or a completely reduced form. The ability of CoQ10 to donate and accept electrons is important for its role in the mitochondrial membrane during ATP synthesis. CoQ10 accepts electrons generated during metabolism and transfer the electrons to electron acceptors. It also transfers protons across the mitochondrial membrane creating a gradient and energy released by proton flow back into the mitochondria forms ATP.
References
Berg, J. M., Tymoczko, J. L., & Stryer, L. (2002). Biochemistry 5th Edition. New York, NY: W
H Freeman and Company.
Crane, F. L. (2001). “Biochemical functions of coenzyme Q10.” Journal of the American
Esposito G, Vitagliano L, Santamaria R, Viola A, Zagari A, Salvatore F (November 2002).
"Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance". FEBS Lett. 531 (2): 152–156.
Janson, L. W., & Tischler, M. E. (2012). Citric Acid Cycle. In The Big Picture: Medical
Biochemistry New York, NY: McGraw-Hill.
