How Yeast Chooses to Breathe or Ferment Based on Fat Molecules

Greg Howard
8th May, 2024

How Yeast Chooses to Breathe or Ferment Based on Fat Molecules

Image Source: Natural Science News, 2024

Key Findings

  • Princeton study finds yeast cells' lipid makeup changes with metabolism type, hinting at health markers
  • Faster growth in yeast leads to less heavy hydrogen in lipids, especially when respiring glycerol
  • Similar patterns in mouse liver cells suggest lipid composition could reveal cell health, aiding cancer research
Understanding the inner workings of cells, particularly how they produce energy and build essential components like lipids, is a cornerstone of both biological research and medical science. A recent study from Princeton University[1] has shed new light on this process by examining the hydrogen isotopic composition of lipids—essentially the ratio of heavy hydrogen (deuterium) to regular hydrogen—in yeast cells. This research not only advances our knowledge of cellular metabolism but also offers a promising method to monitor the health of cells, with potential implications for cancer research. The study's focus is on a cellular compound called NADPH, a key player in the biosynthesis of fatty acids, the building blocks of lipids. NADPH provides the necessary electrons for these biosynthetic reactions, and its hydrogen isotopic composition is influenced by the metabolic pathway that produces it. By studying the yeast Saccharomyces cerevisiae, researchers were able to track changes in the hydrogen isotopic composition of lipids as a reflection of the underlying metabolic processes. Previous research has shown that the D/H ratio of lipids compared to water, known as lipid/water 2H-fractionation, varies significantly with the type of metabolism a cell employs[2][3][4][5]. For instance, heterotrophic growth on sugars typically results in less deuterium in lipids relative to the growth water, while chemoautotrophic and photoautotrophic growth yield lipids more depleted in deuterium[2][4]. These variations have been linked to the fluxes through different enzymes involved in NADPH production[3]. Building on these findings, the Princeton study discovered that in yeast, the 2H-fractionation of fatty acids was over 550‰ higher in cells respiring glycerol compared to those fermenting sugars. This large difference is attributed to the activity of specific enzymes that contribute to NADPH production. For example, the enzyme cytosolic isocitrate dehydrogenase (cIDH) is active during respiration but not fermentation, leading to a significant increase in the 2H-enrichment of lipids when cIDH contributes to NADPH production. Interestingly, the study also found that growth rate impacts the D/H ratio of lipids. Faster-growing yeast cells had lower 2H/1H ratios, especially noticeable in glycerol-respiring cells, where the difference could be as much as 200‰. These variations are thought to be due to shifts in the demand for NADPH, which is used not only for fatty acid synthesis but also for other cellular processes. The relevance of this research extends beyond yeast cells. The same principles were applied to liver cells from mice, where lipids from slower-growing, healthy respiring cells were more 2H-enriched compared to those from fast-growing, fermenting cells typical of hepatocellular carcinoma, a type of liver cancer. This finding suggests that the hydrogen isotopic composition of lipids could serve as a natural marker to differentiate between healthy and diseased states in eukaryotic cells, including human cells. The implications of this study are profound. It provides a non-invasive way to track cellular metabolism and potentially monitor health and disease progression. Cancer cells, for example, are known for their altered metabolism, often showing a preference for fermentation even in the presence of oxygen, a phenomenon known as the Warburg effect. The ability to detect such metabolic shifts through the hydrogen isotopic composition of lipids could open new avenues for diagnosis and treatment monitoring. In conclusion, the research from Princeton University represents a significant step forward in our understanding of cellular metabolism and its connection to health and disease. By showing how the isotopic composition of lipids can reflect different metabolic states, this study not only corroborates earlier findings[2][3][4][5] but also expands the potential applications of this knowledge, offering a promising tool for medical science.

GeneticsBiochemPlant Science

References

Main Study

1) Large enrichments in fatty acid 2H/1H ratios distinguish respiration from aerobic fermentation in yeast Saccharomyces cerevisiae.

Published 14th May, 2024 (future Journal edition)

https://doi.org/10.1073/pnas.2310771121

Related Studies

2) Large D/H variations in bacterial lipids reflect central metabolic pathways.

https://doi.org/10.1073/pnas.0903030106

3) 2H/1H variation in microbial lipids is controlled by NADPH metabolism.

https://doi.org/10.1073/pnas.1818372116

4) Impact of metabolism and growth phase on the hydrogen isotopic composition of microbial fatty acids.

https://doi.org/10.3389/fmicb.2015.00408

5) Fractionation of Hydrogen Isotopes by Sulfate- and Nitrate-Reducing Bacteria.

https://doi.org/10.3389/fmicb.2016.01166


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