The truncated metabolic pathway model

In the “Coherent metabolic pathway”, all of the enzymes are co-expressed to successively generate series of reaction that leads to the end-products synthesis. In this pathway all of the intermediate molecules are short lived as they are catabolized by the downstream enzyme. In the “Truncated metabolic pathway” (lower panel), only the initial members of a given metabolic pathway are expressed giving a rise to the over-production of specific “immature” metabolites, designated “intermetabolites”. We proposed that these intermetabolites function as regulatory molecules.

DHP accumulation during the EMT program

In the liver, the pyrimidine degradation pathway is composed of three enzymes: DPYD, DPYS, and UPB1 (upper panel). The initial substrates of this pathway are the pyrimidines, uracil and thymine, and the final products are -alanine or 2-methyl--alanine. In the liver, DPYD products (DHU and DHT (DHPs)) are then further catabolized by DPYS, which is the only known enzyme to consume these metabolites. During EMT, DPYD is the only enzyme expressed from this pathway resulting in DHP accumulation in cells (lower panel). We previously demonstrated that the accumulation of DHP is essential for the EMT program.