Lovastatin Lowers Serum Cholesterol Levels

Chemists and biochemists have long sought a means of reducing serum cholesterol levels to reduce the risk of heart attack and cardiovascular disease. Because HMG-CoA reductase is the rate-limiting step in cholesterol biosynthesis, this enzyme is a likely drug target. Mevinolin, also known as lovastatin (see figure), was isolated from a strain of Aspergillus terreus and developed at Merck, Sharpe and Dohme for this purpose. It is now a widely prescribed cholesterol-lowering drug. Dramatic...

Prenyl Protein Protease Is a New Chemotherapy

The protein called p21ras or simply Ras is a small GTP-binding protein involved in cell signaling pathways that regulate growth and cell division. Mutant forms of Ras cause uncontrolled cell growth, and Ras mutations are involved in one third of all human cancers. Because the signaling activity of Ras is dependent on prenylation, the prenylation reaction itself, as well as the prote-olysis of the -AAX motif and the methylation of the prenylated Cys residue, have been considered targets for...

The Molecular Basis for the Action of Nonsteroidal Antiinflammatory Drugs

Prostaglandins are potent mediators of inflammation. The first and committed step in the production of prostaglandins from arachidonic acid is the bis-oxygenation of arachindonate to prostaglandin PGG2. This is followed by reduction to PGH2 in a peroxidase reaction. Both these reactions are catalyzed by prostaglandin endoperoxide synthase, also known as PGH2 syn-thase or cyclooxygenase, thus abbreviated COX. This enzyme is inhibited by the family of drugs known as nonsteroidal anti-inflammatory...

Treating Allergies at the Cell Membrane

Allergies represent overreactions of the immune system caused by exposure to foreign substances referred to as allergens. The inhalation of allergens, such as pollen, pet dander, and dust, can cause a variety of allergic responses, including itchy eyes, a runny nose, shortness of breath, and wheezing. Allergies can also be caused by food, drugs, dyes, and other chemicals. The visible symptoms of such an allergic response are caused by the release of histamine (see figure) by mast cells, a type...

Carbohydrate Utilization in Exercise

Carbohydrate Utilization

Animals have a remarkable ability to shift gears metabolically during periods of strenuous exercise or activity. Metabolic adaptations allow the body to draw on different sources of energy (all of which produce ATP) for different types of activity. During periods of short-term, high-intensity exercise (e.g., a 100-m dash), most of the required energy is supplied directly by existing stores of ATP and creatine phosphate (Figure, part a). Long-term, low-intensity exercise (a 10-km run or a...

Exterminator Proteins Biological Pest Control at the

Amide Linked Myristoyl Anchors

Control of biological pests, including mosquitoes, houseflies, gnats, and tree-consuming predators like the eastern tent caterpillar, is frequently achieved through the use of microbial membrane proteins. For example, several varieties of Bacillus thu-rigiensis produce proteins that bind to cell membranes in the digestive systems of insects that consume them, creating transmembrane ion channels. Leakage of Na , K , and H ions through these membranes in the insect gut destroys crucial ion...

Irs1

A number of proteins do not perform any obvious chemical transformation but nevertheless can regulate the ability of other proteins to carry out their physiological functions. Such proteins are referred to as regulatory proteins. A well-known example is insulin, the hormone regulating glucose metabolism in animals. Insulin is a relatively small protein 5.7 kD and consists of two polypeptide chains held together by disulfide cross-bridges. Other hormones that are also proteins include pituitary...

Phosphoric Acid Has Three Dissociable H

Calcium Sulfate Titration Curve

Figure 2.14 shows the titration curve for phosphoric acid, H3PO4. This substance is a polyprotic acid, meaning it has more than one dissociable proton. Indeed, it has three, and thus three equivalents of OH are required to neutralize it, as Figure 2.14 shows. Note that the three dissociable H are lost in discrete steps, each dissociation showing a characteristic pKa. Note that pKj occurs at pH 2.15, and the concentrations of the acid H3PO4 and the conjugate base H2PO4 are equal. As the next...

Waters Unique Role in the Fitness of the Environment

The remarkable properties of water render it particularly suitable to its unique role in living processes and the environment, and its presence in abundance favors the existence of life. Let's examine water's physical and chemical properties to see the extent to which they provide conditions that are advantageous to organisms. As a solvent, water is powerful yet innocuous. No other chemically inert solvent compares with water for the substances it can dissolve. Also, it is very impor-...