METABOLITE

organic compound that is a starting material in, an intermediate in, or an end product of metabolism. Starting materials are substances, usually small and of simple structure, absorbed by the organism as food. These include the vitamins and essential amino acids. They can be used to construct more complex molecules, or they can be broken down into simpler ones. Intermediary metabolites are by far the most common; they may be synthesized from other metabolites, perhaps used to make more complex substances, or broken down into simpler compounds, often with the release of chemical energy. For example, glucose, perhaps the single most important metabolite, can be synthesized in a process called gluconeogenesis, can be polymerized to form starch or glycogen, and can be broken down during glycolysis in order to obtain chemical energy. End products of metabolism are the final result of the breakdown of other metabolites and are excreted from the organism without further change; they usually cannot be used to synthesize other metabolites. Urea, for example, is an end product of protein degradation in man, the other primates, and the Dalmatian dog. Carbon dioxide is usually thought of as an end product of carbohydrate, protein, and fat degradation in aerobic organisms, although technically, carbon dioxide, as carbonic acid, can participate in the biosynthesis of some substances, particularly in plants. Complex substances such as proteins, although end products of a synthetic process, can almost always be broken down again and are usually not considered to be true end products of metabolism. A compound that closely resembles a metabolite in molecular structure but is metabolically inactive is called an antimetabolite; such a substance is often used as a drug in the treatment of malignant disease. When introduced into the body, it is mistaken by the cell for the metabolite it simulates, thus preventing the cell from using the genuine substance necessary to its life and growth. It is difficult to design molecules so that they will be metabolic poisons for malignant cells and not for normal cells as well. Folic acid (see coenzyme) antagonists such as aminopterin and methotrexate are used in the treatment of leukemias and other neoplastic diseases. The purine antagonist mercaptopurine is also used for the treatment of acute leukemia, while azathioprine (Imuran) is used to prevent the rejection of transplanted organs. Pyrimidine antagonists used in cancer chemotherapy include fluorouracil and fluorodeoxyuridine. Most of the agents are designed to halt cell division in rapidly dividing malignant cells by the disruption of the metabolism of purines and pyrimidines, two classes of compounds necessary for nucleic acid synthesis and hence necessary for cell division.

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