Figure 4. Yap reprograms nitrogen metabolism by enhancing GLUL-dependent anabolic assimilation of ammonia for de novo nucleotide biosynthesis.

(a) Clustergram analysis of polar metabolite abundance from dissected WT and lf:Yap livers as determined by LC-MS/MS via selected reaction monitoring (SRM) analysis. n=5 WT and lf:Yap adult livers; see Supplementary Table 4. p<0.05, two-sided Student's t-test, values represent the mean±SEM.

(b) Metabolite Set Enrichment of polar metabolites from WT and lf:Yap livers as determined by SRM analysis.

(c) Steady state abundance of glutamine in WT and lf:Yap livers as determined by SRM analysis. n=10 WT and lf:Yap adult livers; see Supplementary Table 4. *p<0.01, two-sided Student's t-test, values represent the mean±SEM.

(d) Enzymatic assay of glutamine synthetase activity in dissected WT and lf:Yap transgenic livers. n=8 and 13 WT and lf:Yap adult liver lysates respectively; see Supplementary Table 4. *p<0.01, two-sided Student's t-test, values represent the mean±SEM.

(e) Scheme to monitor the relative isotopic enrichment of ¹⁵NH₄Cl in the presence or absence of MSO in liver lysates from WT and lf:Yap transgenics.

(f) Percentage of ¹⁵N-labelled Guanosine isotopologues in WT and lf:Yap transgenic liver lysates following ammonia assimilation in the presence or absence or MSO. n=5 biologically independent WT and lf:Yap adult liver lysates; see Supplementary Table 4. *p<0.05, two-sided Student's t-test, values represent the mean±SEM.

(g) Percentage of ¹⁵N-labelled Cytosine isotopologues in WT and lf:Yap transgenic liver lysates following ammonia assimilation in the presence or absence or MSO. n= 5 biologically independent WT and lf:Yap adult liver lysates; see Supplementary Table 4. Values represent the mean±SEM.