Few mutations attenuate Mycobacterium tuberculosis (Mtb) more profoundly than deletion of its isocitrate lyases (ICLs). However, the basis for this attenuation remains incompletely defined. Mtb's ICLs are catalytically bifunctional isocitrate and methylisocitrate lyases required for growth on even and odd chain fatty acids. Here, we report that Mtb's ICLs are essential for survival on both acet...

JOHN G. JONES,1 MICHAEL A. SOLOMON,2 SUZANNE M. COLE,3 A. DEAN SHERRY,1,3 AND CRAIG R. MALLOY1,2 1Department of Radiology, University of Texas Southwestern Medical Center, Dallas 75235; 2Department of Internal Medicine, University of Texas Southwestern Medical Center and Department of Veterans Affairs Medical Center, Dallas 75216; and 3Department of Chemistry, University of Dallas, Richardson, ...

Normal cells and cancer cells rely on mitochondria for a range of essential functions including production of ATP, biosynthetic intermediates, heme and ironsulfur clusters, and reactive oxygen species (ROS) for signaling. These functions are essential for cell survival and proliferation. Most cancer cells have functional mitochondria to fulfill these essential requirements; however, there is a ...

A 74-year-old woman with type 2 diabetes mellitus developed ketoacidosis within six days of adding metformin to imeglimin treatment. The patient was insulin-sensitive and showed preserved insulin secretion; therefore, insufficiency alone unlikely contribute the development ketoacidosis. Both partially inhibit complex I in mitochondrial respiratory chain. Inhibition respiration can lead tricarbo...

The cerebral tricarboxylic acid (TCA) cycle rate and the rate of glutamine synthesis were measured in rats in vivo under normal physiological and hyperammonemic conditions using 13C NMR spectroscopy. In the hyperammonemic animals, blood ammonia levels were raised from control values of approximately 0.05 mM to approximately 0.35 mM by an intravenous ammonium acetate infusion. Once a steady-stat...