Scientists have discovered that new enzyme complexes can reprogram metabolism and overcome “cell aging”

Senior author Gerardo Ferbeyre said : “HTC protects cells from hypoxia, and hypoxia usually leads to cell death. Importantly, HTC can be hijacked by certain cancer cells to improve their metabolism and resist hypoxic environment and proliferation.” He is the UdeM professor of biochemistry and the chief scientist of CRCHUM, the research center of the university’s teaching hospital. He made this discovery together with Sebastian Igelmann, a doctoral student in his laboratory and the first author of the study.

HTC is composed of three enzymes: pyruvate carboxylase, apple Acid dehydrogenase 1 (malate dehydrogenase 1) and malic enzyme 1 (malic enzyme 1). They are all highly expressed in samples from mouse models of prostate cancer and tissue samples from prostate cancer patients generated by the University of Veterinary Medicine in Vienna, Austria.

Ferbeyre said: “The most interesting thing is that the inhibition of these enzymes prevents the growth of prostate cancer cells, which suggests that HTC may be the development of various cancers including prostate cancer. A key goal of new therapies.”

Most key metabolic cycles were discovered more than 50 years ago, but HTC is still hidden from researchers. Co-author, McGill University researcher and medical professor Ivan Topisirovic said: “We discovered it through the most advanced metabolomics analysis, which is the study of the chemical processes of cell metabolism.”

Scientists can assemble enzyme complexes from purified proteins and obtain biophysical data about their composition. Their next step will be to generate a detailed high-resolution structure of the enzyme complex in order to design drugs that can modulate its function.