Journal: PLOS Computational Biology

Article Title: Mathematical reconstruction of the metabolic network in an in-vitro multiple myeloma model

doi: 10.1371/journal.pcbi.1011374

Figure Lengend Snippet: A . & B . Mass isotopomer distributions from [U- 13 C]Glucose and [U- 13 C]Glutamine tracing. The Mass Isotopomer Distributions represent the relative abundance of each isotope, normalised to the total sum of all possible isotopologues. Glucose-derived metabolite abundances. Data suggests high glycolytic activity in both cells. In JJN-3 cells, pyruvate-derived alanine is much higher than in HS-5 cells. The abundance of pyruvate in JJN-3 cells is also more significant than that of HS-5. It is possible to see that although pyruvate-derived citrate follows the expected TCA cycle, it does not continue downstream as a-ketoglutarate is low in JJN-3 cells. This indicates an interruption of the TCA cycle. C . & D . Mass isotopomer distributions from [U- 13 C]Glucose and [U- 13 C]Glutamine tracing. Glutamine-derived metabolite abundances. Data suggests that the TCA cycle in both cells is supported via anaplerosis, where exogenous glutamine is interconverted to a-ketoglutarate and then incorporated into the TCA cycle.

Article Snippet: 13C-MFA simulations and Monte Carlo parameter estimation were performed using the MATLAB-based graphical user interface isotopomer network compartmental analysis (INCA) suite software under an academic licence issued by Vanderbilt University.

Techniques: Derivative Assay, Activity Assay

Journal: PLOS Computational Biology

Article Title: Mathematical reconstruction of the metabolic network in an in-vitro multiple myeloma model

doi: 10.1371/journal.pcbi.1011374

Figure Lengend Snippet: A . Incorporation of glucose carbons into pyruvate is also altered by co-culture; while HS-5 cells show lower pyruvate incorporation in mono-culture compared to co-culture conditions, there is little change in JJN-3 incorporation. B . When incubated with 13 C 6 Glucose, label enrichment into the TCA cycle metabolite malate in both the myeloma cell line (JJN-3) or BMMSCs (HS-5) indicates a significant increase in oxidative glucose metabolism (m+2 isotopomer) as well as anaplerotic use (m+3 isotopomer). C . Co-culture of BMMSCs and MM cell lines, HS-5 and JJN-3, respectively, results in reduced glucose use compared to either cell type in mono-culture (corrected to cell number), suggesting a more efficient use of glucose carbons when both cells are cultured together. (In-figure referencing: ***; p<0.001, ****;p<0.0001. From Anova and Dunn’s multiple comparison).

Article Snippet: 13C-MFA simulations and Monte Carlo parameter estimation were performed using the MATLAB-based graphical user interface isotopomer network compartmental analysis (INCA) suite software under an academic licence issued by Vanderbilt University.

Techniques: Co-Culture Assay, Incubation, Cell Culture, Comparison