Increase in cyclic-AMP production following FH deletion. (A) Cyclic-AMP level in UOK262 versus UOK262pFH following treatment with the adenylate cyclase activator forskolin alone or in combination with PDEs inhibitor IBMX. (B-C) Gene set enrichment analysis (GSEA) of changes in expression between UOK262 versus UOK262pFH. Specifically, the x-axis represents an ordering of genes based on their drop in expression following FH deletion. The y-axis in the upper graph represents the enrichment of increasing sets of differentially expressed genes with adenylate cyclases (B) or PDEs (C). As shown, the expression of adenylate cyclases does not change significantly following FH deletion (B), while the expression of PDEs significantly drops following FH deletion (C).