Malonyl-CoA, an inhibitor of fatty acid oxidation in skeletal muscle mitochondria, decreases in rat skeletal muscle during exercise or in response to electrical stimulation. Regulation of rat skeletal muscle acetyl-CoA carboxylase (ACC), the enzyme that synthesizes malonyl-CoA, was studied in vitro and in vivo. Avidin-Sepharose affinity-purified ACC from hindlimb skeletal muscle was phosphoryla...

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...

An enzymatic method has been developed for the measurement of malonyl-CoA in perchioric acid extracts of liver. With this method the relative activities of acetyl-CoA carboxylase and fatty acid synthetase have been studied in vivo by comparing the diet-induced changes in malonyl-CoA concentrations with rates of 3Hz0 incorporation into fatty acids. Malonyl-CoA concentrations were low in the fat-...

A 3-hydroxypropionate/4-hydroxybutyrate cycle operates during autotrophic CO(2) fixation in various members of the Crenarchaea. In this cycle, as determined using Metallosphaera sedula, malonyl-coenzyme A (malonyl-CoA) and succinyl-CoA are reductively converted via their semialdehydes to the corresponding alcohols 3-hydroxypropionate and 4-hydroxybutyrate. Here three missing oxidoreductases of ...

Liver acetyl-CoA carboxylase, a biotin-enzyme which catalyzes the ATP-dependent carboxylation of acetyl-CoA (acceptor) to form malonyl-CoA (carboxylated acceptor), decarboxylates malonyl-CoA by a biotin-dependent, as well as a biotin-independent mechanism. Neither ADP, Pi, nor divalent metal ion are required for either of these abortive decarboxylations. The biotin-dependent reaction is blocked...

Fatty acid synthetase complex (Mr = 500,000) purified from pigeon liver homogenates is inactivated by phenylmethylsulfonyl fluoride. A well characterized inhibitor of serine esterases. Pseudounimolecular kinetics are followed at all inhibitor concentrations studied (0.05 to 1.0 mM). The second order rate constant obtained at pH 7.0, 30 degrees in 0.05 M potassium phosphate, 1 mM EDTA is 250 plu...

Intramyocellular lipid content (IMCL) serves as a good biomarker of skeletal muscle insulin resistance (IR). However, intracellular fatty acid metabolites [malonyl-CoA, long-chain acyl-CoA (LCACoA)] rather than IMCL are considered to be responsible for IR. This study aimed to investigate dynamics of IMCL and fatty acid metabolites during fed-to-starved-to-refed transition in lean and obese (IR)...

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,...

Recent work implicated the Escherichia coli BioC protein as the initiator of the synthetic pathway that forms the pimeloyl moiety of biotin (Lin, S., Hanson, R. E., and Cronan, J. E. (2010) Nat. Chem. Biol. 6, 682-688). BioC was believed to be an O-methyltransferase that methylated the free carboxyl of either malonyl-CoA or malonyl-acyl carrier protein based on the ability of O-methylated (but ...