UTP is required for vitamin B1 utilization
Was going through some recent papers and came across this fascinating finding about vitamin B1 metabolism. While we’ve always focused on ATP in cellular energy pathways, these researchers found that UTP (another nucleotide) plays a crucial role in vitamin B1 activation.
What caught my attention was how they demonstrated that UTP, not ATP, is the preferred substrate for TPK1 - the enzyme that activates B1. This honestly changes how we think about vitamin B1 metabolism. The data shows that without adequate UTP, cells can’t properly activate B1, even if there’s plenty of it around.
This could explain some weird cases where patients require B1 supplementation daily. Their cells might have enough B1, but without sufficient UTP, it just sits there inactive. The researchers showed this impacts everything from energy production to fat cell development.
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.