From biochemical textbooks, one can get the impression that cellular metabolism where interconversions of metabolites occur along clearly defined pathways. In these pathways, reactions are catalyzed by exquisitely specific enzymes.
Yet, the reality is different, Many enzymes do not only act on their physiological substrate but also on substrates that are structurally related. This leads to the production of side-products that can be toxic to cells. To prevent this toxicity, dedicated enzymes exist that eliminate these side-products or convert them into useful metabolites. Depending on the context, these enzymes have been termed metabolite repair, clean-up or sanitizing enzymes.
In the last couple of years, our lab has identified several metabolite repair enzymes that play an important role in cellular metabolism. We are convinced that disturbances in metabolite repair enzymes might play a key role in several diseases. Thus our work might reveal novel facets of the pathogenesis of several rare and common diseases.
Published examples from our labs include:
- PGP : a clean-up enzyme required for the parallel action of glycolysis and the pentose phosphate pathway.
- NIT1: elimination of deaminated glutathione
- L2HGDH and D2HGDH: elimination of L- or D-hydroxyglutarate
- ECHDC1: elimination of ethylmalonyl-CoA
- NAXE and NAXD: collaboration of an ancient set of enzymes to eliminate NAD(P)HX