A biologically aggressive subset of human breast cancers and other malignancies is characterized by elevated fatty-acid synthase (FAS) enzyme expression, elevated fatty acid (FA) synthesis, and selective sensitivity to pharmacological inhibition of FAS activity by cerulenin or the novel compound C75. In this study, inhibition of FA synthesis at the physiologically regulated step of carboxylatio...

Malonyl-CoA is an essential intermediate in fatty acid synthesis in all living cells. Here we demonstrate a new role for this molecule as a global regulator of lipid homeostasis in Gram-positive bacteria. Using in vitro transcription and binding studies, we demonstrate that malonyl-CoA is a direct and specific inducer of Bacillus subtilis FapR, a conserved transcriptional repressor that regulat...

Anthocyanins, a class of flavonoids, are responsible for the orange to blue coloration of flowers and act as visual attractors to aid pollination and seed dispersal. Malonyl-CoA is the precursor for the formation of flavonoids and anthocyanins. Previous studies have suggested that malonyl-CoA is formed almost exclusively by acetyl-CoA carboxylase, which catalyzes the ATP-dependent formation of ...

Physiological hyperglycemia with hyperinsulinemia reduces fat oxidation in skeletal muscle. The mechanism responsible for this decrease in fat oxidation in human muscle is not known and may contribute to the development of insulin resistance. We hypothesized that the transfer of long-chain fatty acids (LCFAs) into the mitochondria via carnitine palmitoyltransferase-1 (CPT-1) is inhibited by inc...

Carnitine palmitoyltransferase I, which is expressed in the pancreas as the liver isoform (LCPTI), catalyzes the rate-limiting step in the transport of fatty acids into the mitochondria for their oxidation. Malonyl-CoA derived from glucose metabolism regulates fatty acid oxidation by inhibiting LCPTI. To examine directly whether the availability of long-chain fatty acyl-CoA (LC-CoA) affects the...

Several approaches were used to test the hypothesis proposing a role for acyl-CoA esters in nutrient-induced insulin release (Prentki, M., and Matschinsky, F. M. (1987) Physiol. Rev. 67, 1185-1248; Corkey, B. E., Glennon, M. C., Chen, K. S., Deeney, J. T., Matschinsky, F. M., and Prentki, M. (1989) J. Biol. Chem. 264, 21608-21612). Exogenous saturated long chain fatty acids markedly potentiated...

Production of value-added chemicals in microorganisms is regarded as a viable alternative to chemical synthesis. In the past decade, several engineered pathways producing such chemicals, including plant secondary metabolites in microorganisms have been reported; upscaling their production yields, however, was often challenging. Here, we analyze a modular device designed for sensing malonyl-CoA,...

Administration to normal rats of 100 mg of streptozotocin/kg body weight produced ketotic diabetic rats in which the affinity of carnitine palmitoyltransferase for malonyl-CoA was decreased by 10-fold and its activity was increased by 30%, but the injection of insulin brought the affinity and the activity back to normal within 4 h. Administration of 60 mg of streptozotocin/kg produced non-ketot...

The formation of fusion protein in biosynthetic pathways usually improves metabolic efficiency either channeling intermediates and/or colocalizing enzymes. In the metabolic engineering of biochemical pathways, generating unnatural protein fusions between sequential biosynthetic enzymes is a useful method to increase system efficiency and product yield. Here, we reported a special case. The malo...

background the malonyl-coa decarboxylase (mcd, ec.4.1.1.9) enzyme regulates malonyl-coa levels. the effect of aerial parts extracts of urtica dioica (ud) on mcd is poorly understood. objectives the present experiment was undertaken to evaluate the effect of ud aerial parts extracts on mcd level. materials and methods in this experimental study, two groups of rats were used: normal and hyperglyc...