Influence of PCSK9 on LDL Levels of Bloodstream Using Wild-Type, Mutant 1, and Mutant 2 Allele
Ahmad Mohammed
Abstract Enzyme Proprotein convertase subtilisin/kexin type 9, is also known as PCSK9, this enzyme is encoded by the PCSK9 gene and is responsible for cholesterol homeostasis. High levels of LDL in the bloodstream are correlated with the increased risk of cardiovascular diseases. The hypothesis being tested is if changes in the PCSK9 allele alter the enzymatic activity affecting the cholesterol levels in the bloodstream. Mutant 1 and Wild-type corresponded with normal levels of LDL in blood stream, while Mutant 2 corresponded with high levels of LDL in blood stream.
Introduction
The past decade has brought up a lot…show more content… The significance of this enzyme is its role it plays in the human body to maintain cholesterol homeostasis. Different forms of PCSK9 can reduce or increase circulating cholesterol. When PCSK9 binds to an LDLR, the receptor is destroyed along with the LDL particle, although if PCSK9 does not bind to an LDLR, the receptor can return to the surface of the cell and remove more cholesterol. Other variants of PCSK9 are associated with a rare autosomal dominant familial hypercholesterolemia (HCHOLA3). Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically high amounts of low-density lipoprotein (LDL), also known as the “bad cholesterol” (Lewis 2001). The mutations increase its protease activity, reducing the LDLR levels and preventing the uptake of cholesterol into the…show more content… The PCSK9 enzyme works by reducing the amount of LDRL on the outer cell surface, and therefore increases the amount of LDL in the bloodstream. In this experiment it is assumed that these proteins interact with the LDL receptor (LDLR) similarily such that a change in recycling to the plasma membrane or transport to lysosomes of LDLR is not the reason for changes in circulating LDL levels in these patients. Data for the amount of LDL based on population size for individuals with wild type, mutant 1, and mutant 2 PCSK9 can be seen in Table 1. Once the experiments were conducted the data was used to construct three Michaelis-Menton plots which shows the velocity of the reaction versus the substrate concentration for the different types of PCSK9 enzyme. The Vmax, Km, and Kcat was then calculated using the data which can be seen in Figure 1.
Table 1: Table shows the three protein type and amount of LDL based on the population size. The proteins were chosen based on the LDL levels in patients that were homozygous for one of the allele. The “normal” amount of LDL should be below 120mg/dL and if above 160mg/dL is considered a high amount of
