Bahnsen M, Burrin J M, Johnston D G, Pernet A, Walker M, Alberti K G
Am J Physiol. 1984 Aug;247(2 Pt 1):E173-80. doi: 10.1152/ajpendo.1984.247.2.E173.
Ketogenesis may be controlled at several sites. Lipolysis with release of plasma nonesterified fatty acid (NEFA) substrate is the first step. Plasma NEFA are taken up by the liver in a concentration-dependent fashion and, after conversion to the acyl-CoA derivative, may either be reesterified or enter the mitochondria via the carnitine shuttle. After beta-oxidation the resultant acetyl-CoA may either be converted to ketone bodies that are then released into the circulation or be condensed with oxaloacetate and enter the tricarboxylic acid cycle, the third potential control point. In humans, infusion of epinephrine causes a transient two- to threefold increase in fatty acids, glycerol, and ketone bodies. Insulin levels show a small absolute increase. Norepinephrine has similar effects, although insulin levels tend to be suppressed and glucagon levels rise somewhat. If somatostatin is added simultaneously, the lipolytic and ketogenic effects are accentuated and prolonged. Dopamine, in a high dose, has no effect on ketone bodies alone but shows small increases in NEFA and ketone bodies in the presence of somatostatin and may play a modulatory role in ketogenesis. The ketogenic effect of catecholamines could thus be in the adipocyte or in the liver. Studies with perfused liver or hepatocytes showed only trivial effects on ketogenesis even with supraphysiological doses of catecholamines. Furthermore infusion studies in rats showed decreased rather than increased ketogenesis with no change in NEFA levels. The data suggest that a) there are species differences, and b) in humans epinephrine- and norepinephrine-induced increases in ketogenesis are secondary to increases in NEFA substrate supply.
生酮作用可在多个位点受到调控。脂肪分解并释放血浆非酯化脂肪酸（NEFA）底物是第一步。血浆NEFA以浓度依赖的方式被肝脏摄取，在转化为酰基辅酶A衍生物后，既可以重新酯化，也可以通过肉碱穿梭进入线粒体。经过β氧化后，生成的乙酰辅酶A既可以转化为酮体然后释放到循环中，也可以与草酰乙酸缩合并进入三羧酸循环，这是第三个潜在的控制点。在人类中，输注肾上腺素会导致脂肪酸、甘油和酮体短暂增加两到三倍。胰岛素水平有小幅的绝对升高。去甲肾上腺素也有类似作用，尽管胰岛素水平往往受到抑制，胰高血糖素水平略有升高。如果同时添加生长抑素，脂解和生酮作用会增强并延长。高剂量多巴胺单独对酮体没有影响，但在生长抑素存在的情况下，NEFA和酮体有小幅增加，可能在生酮作用中起调节作用。因此，儿茶酚胺的生酮作用可能在脂肪细胞或肝脏中。对灌注肝脏或肝细胞的研究表明，即使使用超生理剂量的儿茶酚胺，对生酮作用的影响也很小。此外，对大鼠的输注研究表明，生酮作用降低而非增加，NEFA水平没有变化。数据表明：a）存在物种差异；b）在人类中，肾上腺素和去甲肾上腺素诱导的生酮作用增加是NEFA底物供应增加的继发结果。
