Cholesterol is a crucial component of cells, particularly in membranes. However, most cells cannot produce cholesterol on their own, so they rely on obtaining it from the bloodstream. Normally, cholesterol is consumed through the diet and transported in the blood with the help of lipoproteins. Low-density lipoproteins (LDLs) are responsible for carrying cholesterol to cells. These LDLs bind to LDL receptors located on the plasma membrane of cells. Once bound, the receptors collect into "coated pits" and undergo endocytosis in the form of clathrin-coated vesicles. After entering the cell, the endosomes release the LDL and the LDL receptors are recycled back to the cell surface. Inside the cell, LDL is broken down in lysosomes, making cholesterol available for the cell to use. However, defects in the LDL receptor can hinder cellular uptake of LDL. This defect leads to elevated levels of LDL in the bloodstream, commonly referred to as "bad cholesterol." High LDL levels are associated with the development of cholesterol-containing plaques in the smooth muscle layer of arteries, a process known as atherosclerosis. Atherosclerosis increases the risk of heart attacks due to the occlusion of coronary arteries. Secretion is a process where vesicles fuse with the plasma membrane and release their contents. Usually, secretion is triggered by an increase in intracellular Ca++ concentration. However, two exceptions to this rule are renin secretion by juxtaglomerular cells in the kidney and the secretion of parathyroid hormone by the parathyroid gland. Both of these secretions occur with a decrease in intracellular Ca++. The plasma membrane acts as a barrier to the movement of molecules into and out of the cell due to its hydrophobic core. Membrane transport proteins provide pathways that allow for transport to occur. However, transport requires an appropriate driving force in addition to a pathway. This section introduces the basic principles of diffusion, active and passive transport, and osmosis. Diffusion is the process where molecules move from an area of high concentration to an area of low concentration. It occurs whenever a concentration gradient exists, causing molecules to move from high to low concentration, ultimately dissipating the gradient. Diffusion is a random process driven by the thermal motion of molecules. Fick's first law of diffusion describes the rate at which a molecule diffuses from point A to point B. The equation for Fick's first law of diffusion is provided, where J represents the flux or rate of diffusion per unit time, D is the diffusion coefficient, A is the area across which diffusion occurs, ΔC is the concentration difference between point A and B, and ΔX is the distance along which diffusion occurs. The diffusion coefficient takes into account factors such as the thermal energy of the molecule, its size, and the viscosity of the medium in which diffusion takes place. For spherical molecules, the Stokes-Einstein equation is used as an approximation for D.
Cholesterol is an important component of cells (e.g., it is a key component of membranes). However, most cells are unable to synthesize cholesterol and therefore must obtain it from the blood. Normally, cholesterol is ingested in the diet, and it is transported through the blood in association with lipoproteins. Low-density lipoproteins (LDLs) in the blood carry cholesterol to cells, where they bind to LDL receptors in the plasma membrane. After the receptors bind LDL, they collect into “coated pits” and undergo endocytosis as clathrin-coated vesicles. Once inside the cell, the endosomes release LDL and then recycle the LDL receptors back to the cell surface. Inside the cell, LDL is then degraded in lysosomes, and the cholesterol is made available to the cell. Defects in the LDL receptor prevent cellular uptake of LDL. Individuals with this defect have elevated levels of blood LDL, often called “bad cholesterol,” because it is associated with the development of cholesterol-containing plaques in the smooth muscle layer of arteries. This process, atherosclerosis, is associated with an increased risk for heart attacks as a result of occlusion of the coronary arteries.
vesicle to the plasma membrane. The process of secretion is usually triggered by an increase in the concentration of intracellular Ca++ ([Ca++]). However, two notable exceptions to this general rule exist: (1) Renin secretion by the juxtaglomerular cells of the kidney occurs with a decrease in intracellular Ca++ (see ), as does (2) the secretion of parathyroid hormone by the parathyroid gland (see
Basic Principles of Solute and Water Transport
As already noted, the plasma membrane, with its hydrophobic core, is an effective barrier to the movement of virtually all biologically important molecules into or out of the cell. Thus membrane transport proteins provide the pathway that allows transport to occur into and out of cells. However, the presence of a pathway is not sufficient for transport to occur; an appropriate driving force is also required. In this section, the basic principles of diffusion, active and passive transport, and osmosis are presented. These topics are discussed in greater depth, as appropriate, in the other sections of the book.
Diffusion is the process by which molecules move spontaneously from an area of high concentration to one of low concentration. Thus wherever a concentration gradient exists, diffusion of molecules from the region of high concentration to the region of low concentration dissipates the gradient (as discussed later, the establishment of concentration gradients for molecules requires the expenditure of energy). Diffusion is a random process driven by the thermal motion of the molecules. Fick’s first law of diffusion quantifies the rate at which a molecule diffuses from point A to point B:
Equation 1.1 where J = the flux or rate of diffusion per unit time D = the diffusion coefficient A = area across which the diffusion is occurring ΔC = the concentration difference between point A and B ΔX = the distance along which diffusion is occurring
The diffusion coefficient takes into account the thermal energy of the molecule, its size, and the viscosity of the medium through which diffusion is taking place. For spherical molecules, D is approximated by the Stokes-Einstein equation: