Hochachka P W
Science. 1986 Jan 17;231(4735):234-41. doi: 10.1126/science.2417316.
Because aerobic metabolic rates decrease in hypoxia-sensitive cells under oxygen-limiting conditions, the demand for glucose or glycogen for anaerobic glycolysis may rise drastically as a means of making up for the energetic shortfall. However, ion and electrical potentials typically cannot be sustained because of energy insufficiency and high membrane permeabilities; therefore metabolic and membrane functions in effect become decoupled. In hypoxia-tolerant animals, these problems are resolved through a number of biochemical and physiological mechanisms; of these metabolic arrest and stabilized membrane functions are the most effective strategies for extending tolerance to hypoxia. Metabolic arrest is achieved by means of a reversed or negative Pasteur effect (reduced or unchanging glycolytic flux at reduced O2 availability); and coupling of metabolic and membrane function is achievable, in spite of the lower energy turnover rates, by maintaining membranes of low permeability (probably via reduced densities of ion-specific channels). The possibility of combining metabolic arrest with channel arrest has been recognized as an intervention strategy. To date, the success of this strategy has been minimal, mainly because depression of metabolism through cold is the usual arrest mechanism used, and hypothermia in itself perturbs controlled cell function in most endotherms.
在氧气限制条件下，由于缺氧敏感细胞的有氧代谢率降低，作为弥补能量不足的一种方式，无氧糖酵解对葡萄糖或糖原的需求可能会急剧上升。然而，由于能量不足和高膜通透性，离子和电位通常无法维持；因此，代谢和膜功能实际上会脱耦。在耐缺氧动物中，这些问题通过多种生化和生理机制得以解决；其中，代谢停滞和稳定的膜功能是延长对缺氧耐受性的最有效策略。代谢停滞是通过反向或负巴斯德效应（在氧气供应减少时糖酵解通量降低或不变）实现的；尽管能量周转率较低，但通过维持低通透性的膜（可能是通过降低离子特异性通道的密度），代谢和膜功能的耦合是可以实现的。将代谢停滞与通道停滞相结合的可能性已被视为一种干预策略。迄今为止，该策略的成功率极低，主要是因为通过低温降低代谢是常用的停滞机制，而低温本身会扰乱大多数恒温动物中受控的细胞功能。
