Lane M Daniel, Cha Seung Hun
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 512 Wood Basic Science Building, 725 N. Wolfe Street, Baltimore, MD 21205, United States.
Biochem Biophys Res Commun. 2009 Apr 24;382(1):1-5. doi: 10.1016/j.bbrc.2009.02.145. Epub 2009 Mar 3.
In the brain malonyl-CoA serves the important function of monitoring and modulating energy balance. Because of its central role in the metabolism of higher animals, glucose acts as the principal indicator of global energy status. Specialized neuronal nuclei within the hypothalamus sense blood glucose and signal higher brain centers to adjust feeding behavior and energy expenditure accordingly. As the level of glucose entering the brain rises, food intake is suppressed. Energy status information triggered by glucose is transmitted via hypothalamic signaling intermediaries, i.e. AMPK and malonyl-CoA, to the orexigenic/anorexigenic neuropeptide system that determines hunger and energy expenditure. The central metabolism of glucose by the glycolytic pathway generates ATP which produces a compensatory decrease in AMP level and AMPK activity. Since acetyl-CoA carboxylase (ACC) is a substrate of AMPK, lowering AMP increases the catalytic activity of ACC and thereby, the level of its reaction product, malonyl-CoA. Malonyl-CoA signals the anorexigenic-orexigenic neuropeptide system to suppress food intake. Unlike glucose, however, centrally metabolized fructose increases food intake. This paradox results because fructose bypasses the rate-limiting step of glycolysis and uses a rapid ATP-requiring reaction that abruptly depletes ATP and provokes a compensatory rise in AMP. Thus, fructose has the opposite effect of glucose on the AMPK/malonyl-CoA signaling system and thereby, feeding behavior. The fact that fructose metabolism by the brain increases food intake and obesity risk raises health concerns in view of the large and increasing per capita consumption of high fructose sweeteners, especially by youth.
在大脑中，丙二酰辅酶A发挥着监测和调节能量平衡的重要作用。由于葡萄糖在高等动物新陈代谢中起着核心作用，它是整体能量状态的主要指标。下丘脑内的专门神经核感知血糖，并向大脑高级中枢发出信号，以相应地调整进食行为和能量消耗。随着进入大脑的葡萄糖水平升高，食物摄入量会受到抑制。由葡萄糖触发的能量状态信息通过下丘脑信号中介物，即AMPK和丙二酰辅酶A，传递到决定饥饿和能量消耗的促食欲/抑食欲神经肽系统。糖酵解途径对葡萄糖的中枢代谢产生ATP，这会导致AMP水平和AMPK活性出现代偿性降低。由于乙酰辅酶A羧化酶（ACC）是AMPK的底物，降低AMP会增加ACC的催化活性，从而提高其反应产物丙二酰辅酶A的水平。丙二酰辅酶A向抑食欲-促食欲神经肽系统发出信号，以抑制食物摄入。然而，与葡萄糖不同的是，中枢代谢的果糖会增加食物摄入量。这种矛盾的结果是因为果糖绕过了糖酵解的限速步骤，并利用了一个快速消耗ATP的反应，该反应会突然耗尽ATP并引发AMP的代偿性升高。因此，果糖对AMPK/丙二酰辅酶A信号系统以及进食行为的影响与葡萄糖相反。鉴于高果糖甜味剂的人均消费量巨大且不断增加，尤其是年轻人的消费量，大脑对果糖的代谢会增加食物摄入量和肥胖风险这一事实引发了人们对健康的担忧。
