Nav: Home

Yeast makes ethanol to prevent metabolic overload

January 07, 2019

Why do some yeast cells produce ethanol? Scientists have wondered about this apparent waste of resources for decades. Now, University of Groningen scientists think they have 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, which was published in Nature Metabolism on 7 January, could be far-reaching, as it also explains why cancer cells waste energy by producing lactate, known as the Warburg effect.

Cells use nutrients like glucose to make new cells. But sometimes, some of these nutrients are wasted. For example, the yeast Saccharomyces cerevisiae, which is used to produce beer, breaks glucose down into ethanol rather than carbon dioxide. '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. It makes no sense', says Matthias Heinemann, Professor of Molecular Systems Biology at the University of Groningen.

Metabolism

Evolution should have put an end to such a waste of resources, so biologists have tried to find a reason for its existence. 'And similar wastefulness can be seen in other cells', says Heinemann. A widely known example is cancer cells. These fast-growing cells excrete lactate, which is a similar waste of energy. And many bacteria waste energy as well. 'This similarity between different organisms made us wonder whether there was a common denominator.'

Heinemann's field of research is metabolism, the chemical reaction network that generates the building blocks for new cells. He hypothesized that there is an upper rate limit at which cells can operate their metabolism. With his PhD students Bastian Niebel and Simeon Leupold, he modelled the Gibbs energy dissipation in cells. This is the energy released by all chemical reactions taking place in a cell.

Something universal

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. 'This is the point where the cells switch from respiration to fermentation', explains Heinemann.

Heinemann and his team obtained similar results for the gut bacterium E. coli, with a plateau at a comparable level of Gibbs energy dissipation. Heinemann: 'Yeast and E. coli live in completely different environments, yet have about the same dissipation limit that is even at about the same value. 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.' 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.

Damage

So what is causing this limit? 'Part of the energy is dissipated as heat, but this is too little to bother the cells. Our idea is that when enzymes catalyze a chemical reaction, they get a tiny push during the reaction, which makes them move. If they work very fast, this could mean that there is too much movement inside the cells, which could damage certain cellular structures.' Studies on the movement of enzymes inside the cell at different metabolic rates could confirm this.

In the meantime, Heinemann believes that he has now solved the mystery of not just ethanol production in yeast, but also the Warburg effect in cancer cells. Almost a century ago, the late Nobel Laureate Otto Warburg observed that cancer cells have a high rate of glycolysis with lactate excretion. This waste of energy and matter is, Heinemann believes, the 'safety valve': 'There are some experiments going on with drugs that block lactate production as a way to treat cancer. The mechanism of these drugs could be to close the cells' safety valve.'

Entropy

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. And indeed, these yeast species don't produce ethanol', says Heinemann.

The discovery brings to mind a quote from Erwin Schrödinger's seminal work 'What is Life': 'The essential thing in metabolism is that the organism succeeds in freeing itself from all the entropy it cannot help producing while alive.' This statement should be extended, Heinemann says, with the following: 'However, there is an upper rate limit at which cells can free themselves from this entropy, and this limit governs how cells operate their metabolism.'
-end-
Reference: Niebel B, Leupold KES, Heinemann, M: An upper limit in Gibbs energy dissipation governs cellular metabolism, Nature Metabolism, 7 January 2019.

University of Groningen

Related Cancer Cells Articles:

Scientists have identified the presence of cancer-suppressing cells in pancreatic cancer
Researchers have identified cells containing a protein called Meflin that has a role in restraining the progression of pancreatic cancer.
Changes in the metabolism of normal cells promotes the metastasis of ovarian cancer cells
A systematic examination of the tumor and the tissue surrounding it -- particularly normal cells in that tissue, called fibroblasts -- has revealed a new treatment target that could potentially prevent the rapid dissemination and poor prognosis associated with high-grade serous carcinoma (HGSC), a tumor type that primarily originates in the fallopian tubes or ovaries and spreads throughout the abdominal cavity.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
White blood cells related to allergies may also be harnessed to destroy cancer cells
A new Tel Aviv University study finds that white blood cells which are responsible for chronic asthma and modern allergies may be used to eliminate malignant colon cancer cells.
Conversion of breast cancer cells into fat cells impedes the formation of metastases
An innovative combination therapy can force malignant breast cancer cells to turn into fat cells.
Breast cancer cells in mice tricked into turning into fat cells
As cancer cells respond to cues in their microenvironment, they can enter a highly plastic state in which they are susceptible to transdifferentiation into a different type of cell.
Brain cancer: Typical mutation in cancer cells stifles immune response
The exchange of a single amino acid building block in a metabolic enzyme can lead to cancer.
Researchers find prostate cancer drug byproduct can fuel cancer cells
A genetic anomaly in certain men with prostate cancer may impact their response to common drugs used to treat the disease, according to new research at Cleveland Clinic.
Dying cancer cells make remaining glioblastoma cells more aggressive and therapy-resistant
A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy.
An index measures similarity between cancer cells and pluripotent stem cells
The new methodology measures tumor aggressiveness and the risk of relapse, helping doctors plan treatment, according to Brazilian scientists authors of a paper published in a special issue of the journal Cell.
More Cancer Cells News and Cancer Cells Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#540 Specialize? Or Generalize?
Ever been called a "jack of all trades, master of none"? The world loves to elevate specialists, people who drill deep into a single topic. Those people are great. But there's a place for generalists too, argues David Epstein. Jacks of all trades are often more successful than specialists. And he's got science to back it up. We talk with Epstein about his latest book, "Range: Why Generalists Triumph in a Specialized World".
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.