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: