{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sahu U"],"funding":["NIA NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["1484-1492"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11325697"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["383(6690)"],"pubmed_abstract":["Cellular purines, particularly adenosine 5'-triphosphate (ATP), fuel many metabolic reactions, but less is known about the direct effects of pyrimidines on cellular metabolism. We found that pyrimidines, but not purines, maintain pyruvate oxidation and the tricarboxylic citric acid (TCA) cycle by regulating pyruvate dehydrogenase (PDH) activity. PDH activity requires sufficient substrates and cofactors, including thiamine pyrophosphate (TPP). Depletion of cellular pyrimidines decreased TPP synthesis, a reaction carried out by TPP kinase 1 (TPK1), which reportedly uses ATP to phosphorylate thiamine (vitamin B1). We found that uridine 5'-triphosphate (UTP) acts as the preferred substrate for TPK1, enabling cellular TPP synthesis, PDH activity, TCA-cycle activity, lipogenesis, and adipocyte differentiation. Thus, UTP is required for vitamin B1 utilization to maintain pyruvate oxidation and lipogenesis."],"journal":["Science (New York, N.Y.)"],"pubmed_title":["Pyrimidines maintain mitochondrial pyruvate oxidation to support de novo lipogenesis."],"pmcid":["PMC11325697"],"funding_grant_id":["R35 CA197569","T32 CA281953","R35 CA197532","R01 GM135587","P01 AG049665","R01 GM143334"],"pubmed_authors":["Torno MD","Shannon WD","Shilatifard A","Reczek CR","Mishra R","Chandel NS","O'Hara BP","Zhao Z","Gao P","Ben-Sahra I","Asara JM","Sahu U","Villa E"],"additional_accession":[]},"is_claimable":false,"name":"Pyrimidines maintain mitochondrial pyruvate oxidation to support de novo lipogenesis.","description":"Cellular purines, particularly adenosine 5'-triphosphate (ATP), fuel many metabolic reactions, but less is known about the direct effects of pyrimidines on cellular metabolism. We found that pyrimidines, but not purines, maintain pyruvate oxidation and the tricarboxylic citric acid (TCA) cycle by regulating pyruvate dehydrogenase (PDH) activity. PDH activity requires sufficient substrates and cofactors, including thiamine pyrophosphate (TPP). Depletion of cellular pyrimidines decreased TPP synthesis, a reaction carried out by TPP kinase 1 (TPK1), which reportedly uses ATP to phosphorylate thiamine (vitamin B1). We found that uridine 5'-triphosphate (UTP) acts as the preferred substrate for TPK1, enabling cellular TPP synthesis, PDH activity, TCA-cycle activity, lipogenesis, and adipocyte differentiation. Thus, UTP is required for vitamin B1 utilization to maintain pyruvate oxidation and lipogenesis.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-05-29T09:37:33.598Z","creation":"2025-07-13T03:04:39.487Z"},"accession":"S-EPMC11325697","cross_references":{"pubmed":["38547260"],"doi":["10.1126/science.adh2771"]}}