Why do some yeast cells produce ethanol? Scientists have wondered about this apparent waste of resources for decades. In a study published today in Nature Metabolism, University of Groningen scientists present a solution: Yeast cells produce ethanol as a “safety valve” to prevent overload when their metabolic operation reaches a critical level. The implications of this new theory could also explain why cancer cells “waste” energy producing lactate.
“Metabolizing a six-carbon molecule to a two-carbon molecule, rather than to carbon dioxide, means part of the energy and matter stored in glucose is lost,” says senior author Matthias Heinemann.
Evolution should have put an end to such a waste of resources, so biologists have tried to find a reason for its existence. Heinemann and team hypothesized that there is an upper rate limit at which cells can operate their metabolism.
By adding thermodynamics to a model with around 1,000 chemical reactions and combining the model with experimental data, Heinemann was able to determine the Gibbs energy dissipation rate as a function of glucose uptake. At first, the Gibbs energy dissipation increases with increasing rates of glucose consumption, but then a plateau is reached, and at that point, ethanol production starts. The team obtained similar results for the gut bacterium E. coli.
“Yeast and E. coli live in completely different environments, yet have about the same dissipation limit that is even at about the same value,” says Heinemann. “This suggests that this limit is something universal.”
The exact reason for this limit is still unknown, but the scientists have come up with a working hypothesis: “Cellular metabolism has a maximum rate at which it can still operate,” Heinemann says. When this is reached, the cells open a “safety valve” and glucose is broken down to ethanol, acetate, or lactate, leaving part of the energy unused.
Heinemann believes that his theory also applies to cancer. “There are some experiments going on with drugs that block lactate production as a way to treat cancer,” he says. “The mechanism of these drugs could be to close the cells’ safety valve.”
Not all cells need a safety valve, though. “Some yeast strains have a slow glucose uptake, so they will never be in danger of metabolic overload,” Heinemann says. “And indeed, these yeast species don't produce ethanol.”