Biochemistry of Halogenated Carboxylic Acids
Mono-, di-, and tricarboxylic acids are key intermediates in several metabolic pathways. The ability of halogenated analogues of many of these acids to mimic their behavior, or to inhibit critical enzymes required for the processing of these acids, has made such analogues important research tools for the study of a broad spectrum of biological processes. For example, in the 1930s, extensive use of iodoacetic acid as an inhibitor was an important strategy in the elucidation of metabolic pathways. In another example having major impact on biochemistry, the studies on the mechanism of fluoroacetate toxicity carried out by Sir Rudolf Peters in the 1950s spurred intense interest in the development of fluorinated compounds as antimetabolites and mechanistic probes. Over the past few decades, an enormous number of halogenated carboxylic acids have been synthesized, and virtually every aspect of energy metabolism has been studied using such analogues. In this review, topics have been arranged progressively from simple to more complex carboxylic acids, with one exception. Because of the intimate biochemical and historical relationship between fluoroacetate and fluorocitrate, the biochemistry of these compounds will be considered together.
KeywordsPyruvate Kinase Pyruvate Dehydrogenase Malate Dehydrogenase Pyruvate Carboxylase Iodoacetic Acid
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