Journal: Drug metabolism and disposition: the biological fate of chemicals

Article Title: Elucidation of Metabolic and Disposition Pathways for Maribavir in Nonhuman Primates through Mass Balance and Semi-Physiologically Based Modeling Approaches.

doi: 10.1124/dmd.121.000493

Figure Lengend Snippet: Fig. 2. Simplified diagram for the semi-PBPK model of maribavir disposition in cynomolgus monkeys. Numbers in the graph denote physiologic and biologic pro- cesses: (1) transit of substance from stomach to duodenum; (2) transit within the small intestine; (3) transit within the colon and to feces; (4) absorption from the small intestine; (5) conversion of glucuronides to parent, which occurs in the last two compartments of the ileal lumen and throughout the colon; (6) absorption from the colon; (7) biliary excretion of parent; (8) glucuronidation of parent and secretion to duodenal lumen; (9) excretion of glucuronides in urine; (10) transport between the liver and central compartment; (11) transport between the central and peripheral compartments; (12) renal excretion of parent; and (13) all other pathways for parent. The two segments of the jejunum, four segments of the ileum, and five of the colon were not separately depicted in this diagram; the detailed diagram in MATLAB SimBiology is shown in Supplemental Fig. 1. MBV, maribavir (parent); MBV-Gluc, maribavir glucuronides; Met, other metabolites of maribavir.

Article Snippet: The model construction, parameter estimation, simulations, and sensitivity analyses were conducted with SimBiology version 5.7 hosted in MATLAB R2017b with Optimization Toolbox version 8.0 (The Mathworks Inc., Natick, MA).

Techniques:

Journal: Drug metabolism and disposition: the biological fate of chemicals

Article Title: Elucidation of Metabolic and Disposition Pathways for Maribavir in Nonhuman Primates through Mass Balance and Semi-Physiologically Based Modeling Approaches.

doi: 10.1124/dmd.121.000493

Figure Lengend Snippet: Fig. 6. Observed plasma concentration vs. time profiles of maribavir in cynomolgus monkey overlaid with fitted curves [BDC only (A)] or simulations [intact animals (B, C, D, and E)] in MATLAB SimBiology. (A) Observed data in individual BDC animals overlaid with fitted curve; (B) simulated data with a single intravenous administration in intact animals, using fm(Gluc) at 0.728 or 0.853 at both 5-mg/kg and 13-mg/kg doses, overlaid with individually observed data; (C) simulated data with a single p.o. administration in intact animals, using fm(Gluc) at 0.728 at 10-mg/kg dose, overlaid with individually observed data; (D) simulated data with repeated b.i.d. p.o. administration at 10, 30, or 100 mg/kg in intact male animals within the first 8 hours on day 2, using fm(Gluc) at 0.728, overlaid with individually observed data (Koszalka et al., 2002); (E) simulated data with repeated b.i.d. p.o. administrations at 10, 30, or 100 mg/kg in intact male animals within the first 8 hours on day 27, using fm(Gluc) at 0.728, overlaid with individually observed data (Koszalka et al., 2002).

Article Snippet: The model construction, parameter estimation, simulations, and sensitivity analyses were conducted with SimBiology version 5.7 hosted in MATLAB R2017b with Optimization Toolbox version 8.0 (The Mathworks Inc., Natick, MA).

Techniques: Clinical Proteomics, Concentration Assay

Journal: Scientific Reports

Article Title: A new insight into role of phosphoketolase pathway in Synechocystis sp. PCC 6803

doi: 10.1038/s41598-020-78475-z

Figure Lengend Snippet: Schematic representation of the central carbon metabolism network, which was implemented in the multi-level kinetic model of Synechocystis . Blue indicates the reactions catalyzed by phosphoketolase. The model includes the Calvin-Benson cycle, glycogen synthesis (sink from glucose-6-phosphate), photorespiratory pathways, phosphoketolase pathway, glycolysis, the oxidative pentose pathway, Entner–Doudoroff pathway and sink reactions (representing the adjacent pathway and the calculation of biomass production). The reversibility of a particular reaction is indicated by two small arrows. Purple indicates the involved enzymes: RuBisCO ribulose-1,5-bisphosphate carboxylase oxygenase, PGK phosphoglycerate kinase, GAP glyceraldehyde-3-phosphate dehydrogenase, TPI triose-phosphate isomerase, ALDO aldolase, FBPase fructose-1,6 bisphosphatase, PFK phosphofructokinase, TKT transketolase, SBPase sedoheptulose-1,7 bisphosphatase, RPI phosphopentose isomerase, PPE phosphopentose epimerase, PRK phosphoribulokinase, GPI glucose-6-phosphate isomerase, G6PD glucose-6-phosphate dehydrogenase, PGD phosphogluconate dehydrogenase, PGPase phosphoglycolate phosphatase, PKET phosphoketolase, GOX glycolate oxidase, SGAT serineglyoxylate transaminase, HPR hydroxypyruvate reductase, GLYK glycerate kinase, AGT alanineglyoxylate transaminase, TSS tartronatesemialdehyde synthase, TSR tartronatesemialdehyde reductase, SHMT serine hydroxymethyltransferase, GLOX glyoxylate oxidase, PSAT * phosphoserine transaminase, PGM phosphoglycerate mutase, ENO enolase, EDD 6P-gluconate dehydratase, EDA 2-keto-3-deoxygluconate-6-phosphate aldolase (EDD and EDA are currently simplified into a single reaction in the model). Open book symbol indicates an involvement of metabolite in other reaction(s). The scheme was created in SimBiology toolbox of MATLAB 2010b (The MathWorks, Inc., Natick, Massachusetts, United States of America), http://www.mathworks.com .

Article Snippet: The multi-level kinetic model for Synechocystis was developed and simulations were executed using the SimBiology toolbox, Optimization toolbox, Global optimization toolbox and Parallel toolbox of MATLAB (The MathWorks, Inc., Natick, Massachusetts, United States of America).

Techniques: