A study published recently in Molecular Biology of the Cell elucidates how a small metabolite and amino acid, methionine, acts as a growth signal for cells by setting into motion a metabolic program for cell proliferation.
It was earlier thought that as long as enough nutrients are present, cells would continue to grow under the control of different internal signaling programs. However, recent studies show that many small intermediates and products of biological metabolism, commonly called metabolites, can themselves act as signaling molecules and control cell growth programs.
Several studies, especially cancer studies, have hinted that the essential amino acid methionine might be a signaling metabolite. Many cancers seem to depend on it for growth. However, how methionine controls growth is still a mystery. Using budding yeast cells as a simple model system, the research team analyzed gene expression profiles and measured the new synthesis of necessary building blocks.
When methionine is limited, cells do not grow. On the other hand, when methionine is abundant, it acts as a growth signal and triggers a cascade of biochemical events, ultimately leading to cell growth. Methionine activates three key nodes in metabolism: (1) the pentose phosphate pathway, (2) the production of glutamine, and (3) the formation of pyridoxal phosphate (the PPP-GDH-PLP node). These nodes produce a set of critical substrates and co-factors that fuel the production of all other amino acids, as well as nucleotides, which are all critical for growth.
Along with helping to explain the role of methionine in sustaining cell growth, this study might just help clarify why cancer cells are addicted to methionine for their growth. The results also present a new direction for the development of strategies to control the growth of many types of cancer.
Image: A recent study from the Laxman lab elucidates how a small metabolite and amino acid, methionine, acts as a growth signal for cells, by setting into motion a metabolic program for cell proliferation. Image courtesy of Adhish Walvekar and Sunil Laxman, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, India.