CANCER CACHEXIA AND GLUCONEOGENESIS
CANCER CACHEXIA AND GLUCONEOGENESIS
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DOI：
10.1111/j.1749-6632.1974.tb14440.x
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发表时间：
1974-01-01
影响因子：
5.2
通讯作者：
GOLD, J
中科院分区：
文献类型：
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作者：
GOLD, J
要澄清上述问题，需要了解植物的异生作用。这是葡萄糖和其他己糖衍生物在肝脏和肾脏皮质中从含有少于6个碳原子的非碳水化合物来源合成的过程。这些非碳水化合物前体包括乳酸、氨基酸（通常作为蛋白质的分解产物）、柠檬酸盐、琥珀酸盐、丙酸盐、乙酸盐等。葡萄糖异生通常不是一个重要的定量途径，但在各种病理生理条件下可能变得如此，例如：I.低碳水化合物饮食，或禁食，这明显刺激新生儿; 2.繁重的工作或运动，导致肌肉中的乳酸增加，其中大部分被重新转化为葡萄糖; 3.肾上腺皮质类糖皮质激素（氢化可的松和皮质酮）分泌增加，导致蛋白质快速动员，用于肾上腺皮质增生; 4.糖尿病，伴随着蛋白质向碳水化合物的异常高转化率;可能存在其他机制。因此，在异常或不寻常的身体条件下，葡萄糖异生可以代表一个主要的生物合成途径，能够在成人中每天合成高达200 g或更多的葡萄糖，这一数字超过了总的最低每日身体需要量。即使身体处于静息基础状态，乳酸也构成了这些前体的重要部分，这些前体作为再生的底物。例如，在正常休息的成年人中，15%的葡萄糖是由脑和外周肌肉组织代谢产生的乳酸形成的。12 Ja在乳酸的这种“循环”中，由乳酸形成的葡萄糖并不是真正的“新葡萄糖”，因为乳酸最初来源于葡萄糖。因此，乳酸被再循环为葡萄糖，如Meyerhof和科里和科里在1928年最初描述的，并且这种特定的再循环被称为“科里循环”。[14]科里循环在癌症中的重要性增加，因为肿瘤糖酵解形成的大量乳酸进入血液;还有证据表明，乳酸可能对肿瘤发生起促进作用，因为当乳酸是底物时，不会抑制肿瘤发生途径中沿着中间产物的浓度。因此，Reichard及其同事15证明，在晚期癌症患者中，科里循环（乳酸循环）的价值是患有其他疾病的患者的2 - 4倍。在一个宫颈转移癌病例中，乳酸盐再循环为葡萄糖的绝对值为68 mg葡萄糖/kg体重/hr（或约114/天，基于70 kg的人）;
A clarification of the above questions requires an understanding of gluconeogenesis. This is the process by which glucose and other hexose derivatives are synthesized in the liver and kidney cortex from noncarbohydrate sources that contain less than six carbon atoms. These noncarbohydrate precursors include lactic acid, amino acids (usually as breakdown products of protein), citrate, succinate, propionate, oxalacetate, and others. Gluconeogenesis is not normally a quantitatively important pathway but can become so under various physiopathological Conditions, such as: I. a low carbohydrate diet, or fasting, which markedly stimulates gluconeogenesis; 2. heavy work or exercise, which results in increased lactic acid’in the muscles, most of which is reconverted to glucose; 3. increased secretion of glucocortiooids (hydrocortisone and corticosterone) from the adrenal cortex, which causes a rapid mobilization of protein for gluconeogenesis; 4. diabetes mellitus, which is accompanied by an abnormally high rate of conversion of protein to carbohydrates; other mechanisms may exist. Thus, under abnormal or unusual body conditions, gluconeogenesis can represent a major biosynthetic pathway capable of synthesizing up to 200 g or more of glucose per day in the adult, ll a figure in excess of the total minimum daily body requirements.Lactic acid occupies a fundamental position in gluconeogenesis. Even with the body in the resting basal state, lactate constitutes an important fraction of those precursors that act as substrates for gluconeogenesis. For instance, in the normal resting adult, 15% of glucose formed via gluconeogenesis originates from lactic acid, which is derived from the metabolism of brain and peripheral musculature. 12Ja In this “recycling” of lactic acid, the glucose formed from lactic acid is not really “new glucose,” because the lactate originally derived from glucose. Thus, lactic acid is recycled to glucose, as described originally by Meyerhof and by Cori and Cori in 1928, and this specific recycling is referred to as the “Cori cycle.” 14 The Cori cycle assumes increased significance in cancer, because substantial amounts of lactate formed as a result of tumor glycolysis find their way into the blood; there is also evidence that lactate may exert a facilitory action on gluconeogenesis, as inhibiting concentrations of intermediates along the gluconeogenitic pathway do not occur when lactate is a substrate. Thus, Reichard and colleagues15 demonstrated that the value of the Cori cycle (recycled lactate) in less advanced cancer patients was two to four times greater than in patients who suffer from other diseases. In one case of metastatic carcinoma of the cervix, the absolute value of this recycling of lactate to glucose was 68 mg glucose/kg body weight/hr (or approximately 114/day, based on a 70-kg person); in a