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糖和癌的致命關(guān)系

糖和癌的致命關(guān)系

Clifton Leaf 2017-10-19
一項(xiàng)重要的新研究為神秘的瓦伯格效應(yīng)找到了關(guān)鍵線索。

癌細(xì)胞非常討厭,從來(lái)沒(méi)法管,肆意游蕩到不該去的地方顛覆秩序,拉攏老實(shí)守規(guī)矩的健康細(xì)胞一起搞破壞,打破“無(wú)數(shù)”生物規(guī)則。

癌細(xì)胞還很怪異。最詭異的例子之一就是糖分新陳代謝的方式。在氧氣充足的條件下,比如在人體內(nèi),正常細(xì)胞通過(guò)氧化作用來(lái)分解葡萄糖并吸取能量。借助生物化學(xué)轉(zhuǎn)化機(jī)制,細(xì)胞從一個(gè)葡萄糖分子中可提取36個(gè)三磷酸腺苷分子,就好像在人體內(nèi)“提現(xiàn)”(有點(diǎn)類似比特幣——細(xì)胞解開(kāi)一些復(fù)雜的等式,回報(bào)是一些可用來(lái)支付的報(bào)酬)。

然而,(大部分)癌細(xì)胞都做很多生物化學(xué)工作,得到的“報(bào)酬”卻較少。它們通過(guò)一種古老的糖酵解“程序”分解葡萄糖,包括10個(gè)步驟,卻只能從一個(gè)葡萄糖分子中得到兩個(gè)三磷酸腺苷分子。

糖酵解過(guò)程中,細(xì)胞跟黏糊糊的原始祖先一樣,在無(wú)氧環(huán)境下也可以獲得能量。厭氧菌和酵母的原理類似,通過(guò)發(fā)酵從糖中提取能量。但在氧氣充足的環(huán)境中,通過(guò)糖酵解攝取能量仿佛用熨斗熨襪子——付出的努力很多,收益卻非常少。

與此同時(shí),癌細(xì)胞的瘋狂“作亂”又需要大量能量——畢竟,細(xì)胞快速分裂需要充足的生物化學(xué)燃料。因此癌細(xì)胞會(huì)瘋狂地“吞噬”糖分(正因如此,我們經(jīng)常能通過(guò)PET掃描觀察腫瘤,明顯能看到哪些組織在迅速吸收注入體內(nèi)的脫氧葡萄糖)。

20世紀(jì)20年代,德國(guó)生物化學(xué)家?jiàn)W托?瓦伯格首先觀察到了癌細(xì)胞古怪而且有悖直覺(jué)的行為,他將之歸咎于線粒體,也就是細(xì)胞的“能源工廠”(和我最最喜歡的細(xì)胞器)存在的缺陷。實(shí)際上,瓦伯格相信這種反常的有氧糖酵解是癌癥的真正起因,只是他不知道具體如何進(jìn)行以及原因。后來(lái)人們把這種現(xiàn)象稱為“瓦伯格效應(yīng)”。

不過(guò),數(shù)十年來(lái)研究人員早已遺忘這個(gè)概念,一直忙著研究其他癌癥理論框架,想分辨出基因變異的細(xì)胞從而治愈癌癥。但近年來(lái),瓦伯格效應(yīng)以及癌癥新陳代謝理論再次“活躍”起來(lái)。(財(cái)富中文網(wǎng))

譯者:Charlie

審校:夏林

?

Cancer cells are nasty little anarchists. They go where they shouldn’t, subvert authority, co-opt law-abiding cells around them, and break a ton of biological rules in their mindless quest for destruction.

They’re also weird. And one of the most bizarre examples of their rule breaking is how they metabolize sugar. When oxygen is readily available, as it is in the human body, normal cells break down and extract energy from glucose through a process called oxidation. By way of this biochemical machination, cells can extract 36 molecules of ATP, which is like cash money in the body. (Think of it like Bitcoin: Cells do some complex equation-solving and, as a reward, they get something they can spend.)

But cancer cells (mostly) do lots of biochemical work to get less coin. They break down glucose through an ancient 10-step process called glycolysis—which yields them a mere two molecules of ATP for every one of glucose.

With glycolysis, cells can produce energy even in the absence of oxygen, which is what our primordial slime ancestors had to do. It’s also what anaerobic bacteria and yeasts do. They derive energy from sugar by way of fermentation. But in the presence of oxygen, extracting energy from sugar by glycolysis is the equivalent of ironing your socks: It would seem to involve expending a lot of effort for little benefit.

What’s more, cancer cells need gobs of energy to fuel their mad rebellion; rapid cell division, after all, requires plenty of biochemical fuel. And cancer cells gobble up sugar like nobody’s business. (That’s why we’re often able to see tumors on a PET scan, which highlights tissues that rapidly take up an injected sugar called FDG.)

A German biochemist named Otto Warburg, back in the 1920s, was the first to observe these oddball, counterintuitive facts about cancer cells, which he blamed on a defect in their mitochondria, the cell’s energy factories (and my all-time favorite organelles). Indeed, the biochemist believed this aberrant aerobic glycolysis—which later became known as the “Warburg effect”—actually caused cancer, though it wasn’t clear how or why.

The notion was somewhat forgotten for decades, as researchers focused on other theoretical frameworks for cancer and tried to tease out the genetic mutations that transformed cells and drove the disease. But in recent years, the Warburg effect—and the broader metabolic theory of cancer—has had a reawakening. (For those wanting to learn more about it, my friend Travis Christofferson has written an excellent book on the subject.)

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