Chemistry and Biochemistry of (−)-Hydroxycitric Acid from Garcinia

(-)-Hydroxycitric acid (-)-HCA is the principal acid of fruit rinds of Garcinia cambogia, Garcinia indica, and Garcinia atroviridis. (-)-HCA was shown to be a potent inhibitor of ATP citrate lyase (EC 4.1.3.8), which catalyzes the extramitochondrial cleavage of citrate to oxaloacetate and acetyl-CoA: citrate + ATP + CoA --> acetyl-CoA + ADP + P(i) + oxaloacetate. The inhibition of this reaction limits the availability of acetyl-CoA units required for fatty acid synthesis and lipogenesis during a lipogenic diet, that is, a diet high in carbohydrates. Extensive animal studies indicated that (-)-HCA suppresses the fatty acid synthesis, lipogenesis, food intake, and induced weight loss. In vitro studies revealed the inhibitions of fatty acid synthesis and lipogenesis from various precursors. However, a few clinical studies have shown controversial findings. This review explores the literature on a number of topics: the source of (-)-HCA; the discovery of (-)-HCA; the isolation, stereochemistry, properties, methods of estimation, and derivatives of (-)-HCA; and its biochemistry, which includes inhibition of the citrate cleavage enzyme, effects on fatty acid synthesis and lipogenesis, effects on ketogenesis, other biological effects, possible modes of action on the reduction of food intake, promotion of glycogenesis, gluconeogenesis, and lipid oxidation, (-)-HCA as weight-controlling agent, and some possible concerns about (-)-HCA, which provides a coherent presentation of scattered literature on (-)-HCA and its plausible mechanism of action and is provocative of further research.