糖酵解Glycolysis

投资阶段：己糖激酶和磷酸果糖激酶-1 消耗 2 个 ATP，把葡萄糖转化为果糖-1,6-二磷酸，醛缩酶将其裂解为两个三碳糖（磷酸二羟丙酮与甘油醛-3-磷酸，二者可互变）。回报阶段：每个甘油醛-3-磷酸被氧化并磷酸化，经两次底物水平磷酸化生成 2 个 ATP，并生成 1 个 NADH。总计每分子葡萄糖净得 2 ATP。磷酸果糖激酶-1 是最重要的调控点，受 ATP 抑制、AMP 激活。

Investment phase: hexokinase and phosphofructokinase-1 spend two ATP to turn glucose into fructose-1,6-bisphosphate, which aldolase splits into two three-carbon sugars (dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, which interconvert). Payoff phase: each glyceraldehyde-3-phosphate is oxidised and phosphorylated, giving one NADH and, by two substrate-level phosphorylations, two ATP. The net yield is 2 ATP per glucose. Phosphofructokinase-1 is the main control point, inhibited by ATP and activated by AMP.

1897 年布赫纳兄弟发现无细胞的酵母汁也能使糖发酵，打破了发酵必须依赖活细胞的观点，获 1907 年诺贝尔化学奖。1900–1930 年代哈登、扬、恩布登、迈耶霍夫、帕尔纳斯、瓦尔堡等陆续鉴定出各中间产物和酶，到 1940 年整个途径被阐明，因此又称 EMP 途径。迈耶霍夫因肌肉中乳酸生成研究获 1922 年诺贝尔生理学或医学奖。

In 1897 the Buchner brothers found that cell-free yeast juice ferments sugar, overturning the belief that fermentation needs living cells, and Eduard Buchner received the 1907 Nobel Prize in Chemistry. From 1900 to the 1930s Harden, Young, Embden, Meyerhof, Parnas, Warburg and others identified the intermediates and enzymes, and by 1940 the whole pathway was known, hence the name EMP pathway. Meyerhof shared the 1922 Nobel Prize in Physiology or Medicine for work on lactic acid in muscle.

有氧时丙酮酸进入线粒体转化为乙酰辅酶 A，进入三羧酸循环；缺氧时，肌肉中丙酮酸被还原为乳酸，酵母中生成乙醇和 CO₂，以再生 NAD⁺ 使糖酵解持续。癌细胞即使在有氧时也大量进行糖酵解（瓦尔堡效应），这是 ¹⁸F-FDG PET 显像的生物学基础。

With oxygen, pyruvate enters mitochondria, becomes acetyl-CoA and feeds the citric acid cycle; without it, muscle reduces pyruvate to lactate and yeast makes ethanol and CO₂, regenerating NAD⁺ so glycolysis can continue. Cancer cells run glycolysis heavily even with oxygen present (the Warburg effect), the biological basis of ¹⁸F-FDG PET imaging.