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糖和癌的致命关系

Clifton Leaf 2017年10月19日

一项重要的新研究为神秘的瓦伯格效应找到了关键线索。

癌细胞非常讨厌,从来没法管,肆意游荡到不该去的地方颠覆秩序,拉拢老实守规矩的健康细胞一起搞破坏,打破“无数”生物规则。

癌细胞还很怪异。最诡异的例子之一就是糖分新陈代谢的方式。在氧气充足的条件下,比如在人体内,正常细胞通过氧化作用来分解葡萄糖并吸取能量。借助生物化学转化机制,细胞从一个葡萄糖分子中可提取36个三磷酸腺苷分子,就好像在人体内“提现”(有点类似比特币——细胞解开一些复杂的等式,回报是一些可用来支付的报酬)。

然而,(大部分)癌细胞都做很多生物化学工作,得到的“报酬”却较少。它们通过一种古老的糖酵解“程序”分解葡萄糖,包括10个步骤,却只能从一个葡萄糖分子中得到两个三磷酸腺苷分子。

糖酵解过程中,细胞跟黏糊糊的原始祖先一样,在无氧环境下也可以获得能量。厌氧菌和酵母的原理类似,通过发酵从糖中提取能量。但在氧气充足的环境中,通过糖酵解摄取能量仿佛用熨斗熨袜子——付出的努力很多,收益却非常少。

与此同时,癌细胞的疯狂“作乱”又需要大量能量——毕竟,细胞快速分裂需要充足的生物化学燃料。因此癌细胞会疯狂地“吞噬”糖分(正因如此,我们经常能通过PET扫描观察肿瘤,明显能看到哪些组织在迅速吸收注入体内的脱氧葡萄糖)。

20世纪20年代,德国生物化学家奥托•瓦伯格首先观察到了癌细胞古怪而且有悖直觉的行为,他将之归咎于线粒体,也就是细胞的“能源工厂”(和我最最喜欢的细胞器)存在的缺陷。实际上,瓦伯格相信这种反常的有氧糖酵解是癌症的真正起因,只是他不知道具体如何进行以及原因。后来人们把这种现象称为“瓦伯格效应”。

不过,数十年来研究人员早已遗忘这个概念,一直忙着研究其他癌症理论框架,想分辨出基因变异的细胞从而治愈癌症。但近年来,瓦伯格效应以及癌症新陈代谢理论再次“活跃”起来。(财富中文网)

译者:Charlie

审校: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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