Some unanswered questions about the pyrimidine catabolic pathway: The human macrophage perspective

Pyrimidine catabolism has attracted attention in relation to pyrimidine analogs used as anticancer drugs but the absence of a severe phenotype associated with pyrimidine catabolism byproducts did not favor to pursue these efforts. Recently, the discovery that dihydropyrimidine dehydrogenase (DPD) has an oxygen-dependent expression in human macrophages brings the aforementioned pathway to the forefront. Moreover, the finding that thymidine phosphorylase, the direct upstream enzyme to DPD in the pathway, also has a huge expression level in macrophages puts a new perspective on this pathway suggesting to look again at the physiology of intracellular pyrimidine bases catabolism revealing some unanswered questions. In this review, we propose to reassess the known and unknown of the catabolism of pyrimidine base in the light of these new results obtained in human macrophages.