Supplementary File 2: Model of M. tuberculosis metabolism with parameters estimated for a glycerol consumption rate at 0.5 mmol/gDW/h (Model 2). Supplementary File 3: Model of M. tuberculosis metabolism with parameters estimated for a glycerol consumption rate at 1 mmol/gDW/h (Model 3). Supplementary File 4: Comparison between steady-state analyses of Model 1, 2, 3 and FBA flux distributions obtained from the Beste model

under the same experimental conditions. Supplementary File 5: Parameter variability analysis graphs of estimated Inhibitors,research,lifescience,medical kinetic parameters after repeating the genetic algorithm 100 times. Conflict of Interest Conflict of Interest The authors declare no conflict of interest.
AICAR is an intermediate metabolite in the purine de novo synthesis pathway (Figure 1), it is synthesized from succinyl-AICAR (SAICAR) by adenylosuccinate lyase (ASL), an enzyme inhibited by Inhibitors,research,lifescience,medical AICAR through a feedback regulation [2]. As a consequence, massive accumulation

of AICAR is associated with SAICAR accumulation in micro-organisms such as yeast [3] and in a specific human pathology [4]. In the de novo purine synthesis pathway, AICAR is further metabolized to IMP by successive action of AICAR-Transformylase Inhibitors,research,lifescience,medical and IMP Cyclohydrolase, two enzymatic activities which are generally carried on a single protein named ATIC. In micro-organisms, AICAR is also synthesized as a by-product of the histidine biosynthesis pathway (Figure 1). Figure 1 Schematic representation of the de novo purine and histidine pathways in yeast. AICAR: 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl 5′-monophosphate. AICAr: riboside form of AICAR (also named acadesine). AMP: Adenosine

5′-monophosphate; … Under conditions Inhibitors,research,lifescience,medical where AICAR accumulates, riboside and triphosphate derivatives are often found in cellular extracts or body fluids. A patient lacking ATIC activity showed accumulation of large amounts of Inhibitors,research,lifescience,medical AICAR riboside (also known as acadesine or AICAr) in urines and mono- di- and tri-phosphate forms of AICAR in erythrocytes [4]. The enzyme(s) dephosphorylating AICAR monophosphate to its riboside form is not identified yet, but it is clear that adenosine kinase can reverse Phosphatidylinositol diacylglycerol-lyase the reaction and phosphorylate AICAR riboside to the monophosphate form [5]. Synthesis of ZTP (triphosphate form of AICAR) was found to occur directly from AICAR through the catalytic action of PRPP-synthetase [6]. Consequently, ZDP (diphosphate form of AICAR) detected in erythrocytes is likely to result from ZTP degradation and to appear upon intracellular degradation or during metabolite extraction, rather than be a ZTP synthesis intermediate. In the early eighties, ZTP was 10058 F4 proposed to be an “alarmone” signaling folate deficiency in Salmonella typhimurium [1] but a later study did not confirm such a role for ZTP in Escherichia coli [7]. 3.