Part A
How Enzymes Act As Protein Catalysts in Biochemical Processes
Catalysis refers to the speeding up of a chemical reaction by a catalyst. A catalyst is a substance that accelerates a chemical reaction but does not undergo a permanent chemical change in the process. Enzymes are catalysts whose building blocks are amino acids: they are proteins. Enzymes also exhibit a defined three-dimensional structure. In addition, they have a cleft on their surface called active site. The active site is the region where substrate interactions take place. Enzymes play important roles in fructose metabolism. The first step of fructose metabolism in the liver is the phosphorylation of fructose. This process is catalysed by enzyme fructokinase. The second step involves the breakdown of fructose-1-phospahte (F1P) into glyceraldehyde and dihydroxyacetone phosphate by enzyme aldolase B.
Enzyme catalysis is based on two main principles: lowering of activation energy and favouring of the formation of transition state (Cooper, 2000). Based on the two principles, enzyme catalysis takes place through any of the four main mechanisms. First, catalysis can take place when one substrate molecule binds to the active site of an enzyme. In this case, the molecule first binds non-covalently through ionic bonds, hydrogen bonds, or hydrophobic bonds. Later, multiple mechanisms that convert the substrate into the final product of the reaction take place.
In another mechanism, two or more different substrates are involved. This mechanism is more common than the one discussed above since most biochemical processes involve the reaction between two or more different substrate molecules (Cooper, 2000). In this case, the reacting molecules come together in proper orientation using the enzyme as a template to favour the formation of transition state (Cooper, 2000).
Another mechanism involves the alteration of the substrate conformation in order to conform to that of the transition state. In this case, the substrate with proper orientation fits properly into the active site of an enzyme (Gropper, Smith, and Groff, 2009). This mechanism can be explained through lock-and-key model. Alternatively, the interactions between the reacting substrate molecules may take place through the modification of the configurations of the substrate molecules in a process called induced fit.
Lastly, enzyme catalysis may take place through the reaction between substrate molecules and specific amino acid side chains found in the active sites of the enzyme. In this case, intermediary bond is formed. The bond is later broken and a product is formed (Murray, 2012).
How a Deficiency in Aldolase B is Responsible for Hereditary Fructose Intolerance (HFI)
Aldolase B is the only enzyme responsible for the breakdown of fructose-1-phosphate. Its deficiency is mainly caused by the mutation of ALDOB gene. Aldolase B deficiency leads to the accumulation of fructose-1-phosphate in the cells of the liver. This accumulation causes toxicity to the liver cells. Consequently, the death of liver cells ensues. Further accumulation causes further damage to the liver hence resulting into conditions such as jaundice, liver cirrhosis, and hepatomegaly. High levels of fructose-1-phosphate also cause symptoms such as sweating, nausea, vomiting, hypoglycaemia, and abdominal pain.
Diagrams
- The lock and key model
Figure 1. Lock and key diagram showing the binding and release of substrate
- Effect of enzymes on activation energy
Figure 2. Effect of enzyme on activation energy. Adapted from The cell: A molecular approach by Cooper, G. M., 2000
Specific Substrate Acted on by Aldolase B during the Metabolism of Fructose
One of the substrates acted on by aldolase B during fructose metabolism in the liver is Fructose-1-phosphate. Fructose-1-phosphate is formed through the phosphorylation of fructose in the liver. It can also be formed from glycogen through the action of glycogen phosphorylase. Fructose-1-phosphate is an intermediate product formed during fructose metabolism. However, it is toxic if present in high levels in the liver cells. In this case, it causes inhibition of glycogen breakdown and glucose synthesis. Consequently, symptoms such as nausea, sweating, and abdominal pain result. Deficiency of aldolase B causes the accumulation of fructose-1-phosphate in the liver cells.
The Role of Aldolase B in the Metabolism of Fructose
Aldolase B acts on fructose-1-phosphate and fructose-1, 6-bisphophate in fructose metabolism to produce three main products: glyceraldehyde, Glyceraldehyde-3-phosphate, and dihydroxyacetone phosphate. Glyceraldehyde and dihydroxyacetone phosphate then form Glyceraldehyde-3-phosphate. Glyceraldehyde-3-phosphate then continues through the glucose metabolism pathway for energy synthesis.
Part B
- Explain what would hypothetically happen to the amount of ATP available to a cell if the entire Cori cycle (glucose going to lactate and then back to glucose) were to occur and remain within that single cell (i.e., a muscle cell).
If Cori cycle were to occur and remain in one given muscle cell, there would be a deficit of 4 ATP molecules in the cell. This situation would arise because the second half of Cori cycle, that involves gluconeogenesis, requires 6 molecules of ATP to take place while the first cycle, glycolysis, produces only 2 molecules of ATP.
- Create an original dynamic diagram that shows why the citric acid cycle (CAC) is central to aerobic metabolism and how it leads to ATP production.
Figure 3 citric acid cycle
- Explain where in the citric acid cycle a hypothetical defect of an enzyme could occur that would decrease the overall ATP production of the mitochondria, including the consequences of the defect
A hypothetical defect of enzyme that would decrease the overall ATP production would take place at the formation of citrate. In this case, the defect would involve enzyme citrate synthase. As a result of the defect, few or no molecules of citrate would be formed. If the former occurs, the number of ATP molecules would be small.
- Explain the specific role of coenzyme Q10 in ATP synthesis as part of the electron transport chain.
Coenzyme Q10 acts as an electron carrier that enables the transport of electrons from enzyme complex 1 and complex 11 to complex 11 in the electron transport chain. This process leads to the pumping of hydrogen ions across the mitochondrial membrane creating proton gradient. Consequently, this process enables ATP synthase, located on the membrane, to synthesise ATP.
ReferencesTop of Form
Cooper, G. M. (2000). The cell: A molecular approach. Washington, D.C: ASM Press.
Gropper, S. A. S., Smith, J. L., & Groff, J. L. (2009). Advanced nutrition and human metabolism. Belmont, Calif: Wadsworth/Cengage Learning.
Murray, R. K. (2012). Harper's illustrated biochemistry. New York: McGraw-Hill Medical.
