Structure and function of plasma membrane

The major components of the plasma membrane include:

• Phospholipids

• Cholesterol

• Carbohydrates

The basic structure of the plasma membrane is formed by phospholipids (Figure 2.1), which are one of the more abundant of the membrane components. Phospholipids are amphipathic molecules that have polar (water-soluble) and nonpolar (water-insoluble) regions. They are composed of a phos-phorylated glycerol backbone, which forms a hydrophilic polar head group and a nonpolar region containing two hydrophobic fatty acid chains. In an aqueous environment such as the body, these molecules are arranged in a formation referred to as the lipid bilayer consisting of two layers of phospho-lipids. The polar region of the molecule is oriented toward the outer surface of the membrane where it can interact with water; the nonpolar, hydrophobic fatty acids are in the center of the membrane away from the water. The functional significance of this lipid bilayer is that it creates a semipermeable barrier. Lipophilic, or nonwater-soluble, substances can readily cross the membrane by simply passing through its lipid core. Important examples of these substances include gases, such as oxygen and carbon dioxide, and fatty acid molecules, which are used to form energy within muscle cells.

Most hydrophilic, or water-soluble, substances are repelled by this hydrophobic interior and cannot simply diffuse through the membrane. Instead, these substances must cross the membrane using specialized transport mechanisms. Examples of lipid-insoluble substances that require such mechanisms include nutrient molecules, such as glucose and amino acids, and all species of ions (Na+, Ca++, H+, Cl-, and HCO3). Therefore, the plasma membrane plays a very important role in determining the composition of the intracellular fluid by selectively permitting substances to move in and out of the cell.

EXTRACELLULAR FLUID

EXTRACELLULAR FLUID

Figure 2.1 Structure of the plasma membrane. The plasma membrane is composed of a bilayer of phospholipid molecules. Associated with this bilayer are intrinsic proteins embedded within and spanning the membrane as well as intrinsic proteins found on the external or internal surface of the membrane. Molecules of cholesterol are found in the inner, nonpolar region of the membrane.

Figure 2.1 Structure of the plasma membrane. The plasma membrane is composed of a bilayer of phospholipid molecules. Associated with this bilayer are intrinsic proteins embedded within and spanning the membrane as well as intrinsic proteins found on the external or internal surface of the membrane. Molecules of cholesterol are found in the inner, nonpolar region of the membrane.

Pharmacy application: lipid solubility and drug elimination

The lipid solubility of many substances can change when physiological conditions vary. For example, the surrounding pH can determine whether a molecule is in a protonated form (positively charged, lipid insoluble) or in an unprotonated form (uncharged, lipid soluble). As discussed, charged substances do not readily cross the membrane, as do uncharged substances. This principle regarding lipid solubility is used in the treatment of an overdose of phenobarbital, a barbiturate used for sedation and seizure disorders. At the normal blood pH of 7.4, the phenobarbital molecules are 50% protonated and 50% unprotonated. Only the uncharged form can cross cell membranes to leave the blood and enter the kidney for excretion in the urine. Treatment with sodium bicarbonate increases the pH of the blood causing many of the protonated phenobarbital molecules to lose their proton and become unprotonated. Therefore, an alkaline environment increases the percentage of uncharged phenobarbital molecules; increases the lipid solubility of these molecules; and facilitates their elimination by the kidneys.

Another important aspect of the lipid bilayer is that the phospholipids are not held together by chemical bonds. This enables molecules to move about freely within the membrane, resulting in a structure that is not rigid in nature, but instead, very fluid and pliable. Also contributing to membrane fluidity is the presence of cholesterol. Cholesterol has a steroid nucleus that is lipid soluble. Therefore, these molecules are found in the interior of the membrane lying parallel to the fatty acid chains of the phospholipids (see Figure 2.1). As such, they prevent the fatty acid chains from packing together and crystallizing, which would decrease membrane fluidity.

Membrane fluidity is very important in terms of function in many cell types. For example, skeletal muscle activity involves shortening and lengthening of muscle fibers. Furthermore, as white blood cells leave the blood vessels and enter the tissue spaces to fight infection, they must squeeze through tiny pores in the wall of the capillary requiring significant deformation of the cell and its membrane. Finally, in all cells, many processes that transport substances across the plasma membrane require the embedded proteins to change their conformation and move about within the bilayer. In each case, in order for the cell membrane, or the entire cell, to change its shape, the membrane must be very fluid and flexible.

Proteins are also associated with the lipid bilayer and essentially float within it. Intrinsic proteins are embedded within and span the membrane, and extrinsic proteins are found on the internal or external surface of the membrane (see Figure 2.1). These proteins provide a variety of important cellular functions by forming the following structures:

• Carrier molecules

• Chemical receptors

Some proteins may form channels through the cell membrane that allow small, water-soluble substances such as ions to enter or leave the cell. Other proteins may serve as carrier molecules that selectively transport larger water-soluble molecules, such as glucose or cellular products, across the membrane. Regulators of specific chemical reactions, enzymes are extrinsic proteins found on the internal (e.g., adenylate cyclase) or external (e.g., acetylcholinesterase) surfaces of the membrane. Chemical receptors are found on the outer surface of the cell membrane and selectively bind with various endogenous molecules as well as with drugs. Through receptor activation, many substances unable to enter the cell and cause a direct intracellular effect may indirectly influence intracellular activity without actually crossing the membrane. Other proteins found on the external surface of the plasma membrane are antigens. These molecules serve as cell "markers" that allow the body's immune system to distinguish between its own cells and foreign cells or organisms such as bacteria and viruses.

The plasma membrane contains a small amount of carbohydrate (2 to 10% of the mass of the membrane) on the outer surface. This carbohydrate is found attached to most of the protein molecules, forming glycoproteins, and to some of the phospholipid molecules (<10%), forming glycolipids. Consequently, the external surface of the cell has a carbohydrate coat, or glycocalyx.

These carbohydrate moieties have several important functions, including:

• Repelling negatively charged substances: many of the carbohydrates are negatively charged, creating an overall negative charge on the surface of the cell that repels negatively charged extracellular molecules.

• Cell-to-cell attachment: the glycocalyx of one cell may attach to the glycocalyx of another cell, which causes the cells to become attached.

• Receptors: carbohydrates may also serve as specific membrane receptors for extracellular substances such as hormones.

• Immune reactions: carbohydrates play a role in the ability of cells to distinguish between "self" cells and foreign cells.

Pharmacy application: hydrophilic drugs bind to receptors

Many substances within the body, including hormones and neurotransmitters, are hydrophilic and therefore incapable of entering the cells to carry out their effects directly. Instead, they bind to their specific receptors on the cell surface. This receptor binding then elicits a series of intracellular events that alter cell function and cell metabolism. Often instances occur in which it would be advantageous to enhance or to inhibit these activities; therefore, drugs may be designed to bind to these specific receptors. A drug that binds to and stimulates a receptor and mimics the action of the endogenous chemical substance is referred to as a receptor agonist. An example is albuterol sulfate, a selective beta2-adrener-gic receptor agonist, which causes dilation of the airways in a patient experiencing an asthmatic attack. A drug that binds to and blocks a receptor, preventing the action of the endogenous substance, is referred to as a receptor antagonist. An example in this case is cimetidine hydrochloride, which inhibits histamine H2 receptors on parietal cells in the stomach, thus reducing gastric acid output. This medication is used to treat patients with a peptic ulcer or gastroesophageal reflux disease (GERD).

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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