Intracellular 1-carbon metabolism (simplified), emphasizing pathways relevant to the text. Multiple significant alterations in gene expression in this metabolic pathway were observed. Enzyme gene names are shown in capital letters, upregulated genes are shown in green and downregulated genes red, genes whose expression did not change are shown in black. Major end-products relevant to the discussion are in bold italics. Methionine adenosyltransferase 2b (MAT2b) is upregulated but all other genes whose expression were altered were downregulated. Notably thymidylate synthase (TYMS),dihydrofolate reductase (DHFR) and 2 de novo DNA methyltransferases 3A and 3B (DNMT3A and DNMT3B) are downregulated. CTH (cystathionine lyase) is reduced as well. The function of the gene product of AHCYL1 (S-adenosylhomocysteine hydrolase-like 1) is not known with certainty but a highly homologous protein catalyzes the reversible hydrolysis of S-adenosylhomocysteine (S-Adohcy) to adenosine and L-homocysteine. Additional genes that were downregulated include folate receptor 1 (FOLR1); gamma glutamyl hydrolase (‘conjugase’,GGH), an enzyme that cleaves the polyglutamyl tail of folates; methylenetetrahydrofolate dehydrogenease (MTHFD1), which is involved in the interconversion of 1-carbon derivatives of tetrahydrofolate; 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), which regenerates an active form of methionine synthase (MTR) via reductive methylation with vitamin B12 as cofactor; and phosphoribosylglycinamide formyltransferase (GART), which is pivotal in purine biosynthesis. THF = tetrahydrofolate; S-AdoMet = S-adenosylmethionine; S-AdoHcy = S-adenosylhomocysteine.