Fig. 2: Hexokinase isoenzyme switch in Huh7 cells induces extended modifications of metabolic connections.

a Western-blot analysis of HK1, HK2, HK3 and GCK expression in Huh7 and Huh7-GCK⁺/HK2⁻. b Hexokinase activity in homogenates of Huh7 and Huh7-GCK⁺/HK2⁻ cells. Means ± SEM are presented (n = 3). c Number of genes changing their expression pattern in Huh7 and Huh7-GCK⁺/HK2⁻ cells (see Supplementary Data 2 for details). d Heatmap showing clustering enrichment scores of the networks obtained when mapping differentially expressed genes to the human metabolic model Recon2. Clustering enrichment scores from the highest in red to the lowest in blue were calculated for different gene expression thresholds (Log₂ | FC | ) and percentages of retained currency metabolites. e Gene network corresponding to the maximal clustering enrichment score (Log₂ | FC | > 3; removed currency metabolites = 2%). The transcription of nodes in green was upregulated and those in red downregulated in Huh7-GCK⁺/HK2⁻ compared to Huh7 cells. Plain edges mark co-regulation between nodes and broken edges inverse regulation at the transcriptional level.