Cancer cell metabolism has been perceived as somewhat of a conundrum for more than a century. Recent findings from Washington University in St. Louis academics suggest that it might not be an abnormality at all. The work was released in Molecular Cell on August 15.
One of the most crucial nutrients in the body is glucose, a common sugar found in diet. It tends to be devoured by cancer cells at an astonishing rate. That appears reasonable at first because cancer cells need to synthesise a lot of things. Because cancers spread quickly, every cell must duplicate every component within it.
But there's a problem. The glucose isn't utilised well by cancer cells. Instead of extracting every ounce of energy they can from glucose, they release the majority of it as waste.
Gary Patti, the Michael and Tana Powell Professor of Chemistry in Arts & Sciences, as well as of genetics and medicine at the School of Medicine, explained that in order for cells to get the most energy possible from glucose, they must move its transformation products into mitochondria. The senior author of the current study is Patti, who works at the Siteman Cancer Center at Barnes-Jewish Hospital and the School of Medicine.
The metabolism is expected to adhere to specific biochemical laws. Thinking about the potential reasons cancers could be permitted to destroy them has been intriguing, Patti said. But the results we provide here show that cancer cells do adhere to established rules.
The tiniest compartments inside cells known as mitochondria are frequently referred to as the cell's power plants or powerhouses. They have strict controls over what enters and leaves them.
To provide some context, in the 1920s a renowned biochemist by name of Otto Warburg made the initial discovery of the wastefulness of tumours. He proposed that damaged mitochondria occur in cancer cells as a solution to the puzzle of why more energy isn't derived from glucose.
We now understand that this is untrue. In fact, most tumours have functional and active mitochondria, according to Patti. But that doesn't explain why cancer cells metabolise so little of the glucose they eat in mitochondria, which is a bothersome and enduring conundrum.
What has perplexed researchers, according to Patti, is the idea that cancer cells choose not to metabolise glucose in their mitochondria. The idea has frequently been that cancer cells desire to use glucose wastefully, whether as a result of Warburg's original thought or perhaps because it occurs so frequently.
There are a variety of justifications for why cancer cells could desire to waste their glucose. Patti and his group assert that these justifications might not be essential. In the end, scientists may be wrong about how odd cancer metabolism is.
Cancer cells actively metabolise glucose in their mitochondria because they genuinely desire to. as long as they can.
Nearly all of the glucose that is restricted from being absorbed by cancer cells ends up in mitochondria, according to Patti. However, as glucose consumption rises, the rate at which molecules produced from glucose are transported into mitochondria can't keep up.
In other words, glucose is only wasted away by cancer cells because mitochondrial transport is too sluggish.
Imagine a bathtub faucet that is shooting out water at a rate that exceeds the capacity of the drain. The water eventually overflows onto the floor.
This metabolic paradigm is not entirely new. Most cells do favour oxidising glucose in their mitochondria over excreting it as waste, according to Patti. "Our findings imply that cancer cells are a common occurrence. They resemble other cells in that they seem to follow similar biochemical pathways.
The breakthrough revealed by the Patti team was made possible by the potent technique known as metabolomics.
Patti stated that the last ten years have seen "amazing breakthroughs in the field of metabolomics and mass spectrometry." "We are currently at a stage where it is even possible to measure chemicals in single cells."
In this work, metabolomics and stable isotope tracers were integrated. This made it possible for researchers to tag various components of glucose and monitor it inside of cells while observing the rate at which substances entered mitochondria or were ejected from cells. Scientists made this discovery when they noticed that cancer cells were outpacing or becoming saturated with the regular fuel transport channels.