2019-07-03 作者:亦菲小妹   |   浏览(502)

   “These experiments revealimportant details that reinforce our fundamental understanding ofthe metabolic underpinnings of molecular biosynthesis and cellularproliferation,” says Jared Rutter, a professor of biochemistry atthe University of Utah who was not involved in the research. “TheMIT team has performed a rigorous and quantitative assessment ofthe contributions of glucose, glutamine, and other molecules to themass of proliferating mammalian cells in culture.”

The findings offer a new way tolook at cancer cell metabolism, a field of research that scientistshope will yield new drugs that cut off cancer cells’ ability togrow and divide.


Vander Heiden’s lab is nowpursuing a more comprehensive understanding of how the Warburgeffect may help cells reproduce. “It refocuses the question,” hesays. “It isn’t necessarily about how the Warburg effect helpscells put glucose into cell mass, but more about why doesglucose-to-lactate conversion help cells use amino acids to buildmore cells.”




Although initially surprising,the findings make sense, Vander Heiden says, because cells are mademostly of protein.

Since the 1920s, scientistshave known that cancer cells generate energy differently thannormal cells, a phenomenon dubbed the “Warburg effect” after itsdiscoverer, German biochemist Otto Warburg. Human cells normallyuse glucose as an energy source, breaking it down through a seriesof complex chemical reactions that requires oxygen. Warburgdiscovered that tumor cells switch to a less efficient metabolicstrategy known as fermentation, which does not require oxygen andproduces much less energy.

“There’s some economy inutilizing the simpler, more direct route to build what you’re madeout of,” he says. “If you want to build a house out of bricks, it’seasier if you have a pile of bricks around and use those bricksthan to start with mud and make new bricks.”





To determine where cells,including those in tumors, were getting the building blocks theyneeded, the researchers grew several different types of cancercells and normal cells in culture dishes. They fed the cellsdifferent nutrients labeled with variant forms of carbon andnitrogen, allowing them to track where the original molecules endedup. They also weighed the cells before and after they divided,enabling them to calculate the percentage of cell mass contributedby each of the available nutrients.


科技新闻---氨基酸能为肿瘤细胞提供最多的“积木科技的新闻 ”



Scientists Reveal Amino Acids Supply Most Building Blocks for TumorCells科学家们发现氨基酸能为肿瘤细胞提供最多的“积木”

Burning up

Refocusing thequestion

“This led us to conclude thatthe importance of high glucose consumption is not necessarily themanipulation of carbon that allows you to make cell mass, but morefor the other products that it provides, such as energy,” Hosiossays.



New research shows that aminoacids, not glucose, account for the majority of cell mass inproliferating mammalian cells.



“Because mammals eat such adiversity of foods, it seemed like an unanswered question aboutwhich foods contribute to what parts of mass,” Vander Heidensays.


Although cells consume glucoseand the amino acid glutamine at very high rates, the researchersfound that those two molecules contribute little to the mass of newcells — glucose accounts for 10 to 15 percent of the carbon foundin the cells, while glutamine contributes about 10 percent of thecarbon. Instead, the largest contributors to cell mass were aminoacids, which make up proteins. As a group, amino acids (excludingglutamine) contribute the majority of the carbon atoms found in newcells and 20 to 40 percent of the total mass.


More recently, scientists havetheorized that cancer cells use this alternative pathway to createbuilding blocks for new cells. However, one strike against thishypothesis is that much of the glucose is converted into lactate, awaste product that is not useful to cells. Furthermore, there hasbeen very little research on exactly what goes into the compositionof new cancer cells or any kind of rapidly dividing mammaliancells.

“If you want to successfullytarget cancer metabolism, you need to understand something abouthow different pathways are being used to actually make mass,” saysMatthew Vander Heiden, the Eisen and Chang Career DevelopmentAssociate Professor of Biology and a member of MIT’s Koch Institutefor Integrative Cancer Research.

Scientists had believed thatmost of the cell mass that makes up new cells, including cancercells, comes from that glucose. However, MIT biologists have nowfound, to their surprise, that the largest source for new cellmaterial is amino acids, which cells consume in much smallerquantities.

It remains something of amystery why proliferating human cells consume so much glucose.Consistent with previous studies, the researchers found that mostof the glucose burned by these cells is excreted aslactate.

目前,作为细胞团的氨基酸(不包括谷氨酰胺)所占比例很高,而谷氨酰胺约占10%。相反,葡萄糖占10-15%,在细胞的碳中,但研究人员发现这两种分子在新细胞质中所占比例极小, 尽管细胞消耗葡萄糖和氨基酸谷氨酰胺的速度很快, Cancer cells are notorious fortheir ability to divide uncontrollably and generate hordes of newtumor cells. Most of the fuel consumed by these rapidlyproliferating cells is glucose, a type of sugar.