Tyson J J
J Theor Biol. 1983 Jul 21;103(2):313-28. doi: 10.1016/0022-5193(83)90031-0.
During exponential growth of a cell culture, some enzymes are synthesized periodically. In a synchronous culture, in which all cells undergo DNA synthesis and division more-or-less synchronously, the burst of enzyme synthesis also occurs synchronously in each cell once per division cycle. However, there are a number of interesting cases in which periodic enzyme synthesis continues in the absence of synchronous DNA replication or cell division. In all cases of periodic enzyme synthesis in asynchronous cultures, the time between bursts of enzyme synthesis, though no longer identical to the cell cycle time, is still close to the interdivision time of the growing, replicating cells. The theory of oscillatory repression looks for an explanation of this phenomenon in the periodic repression of gene transcription caused by periodic fluctuations in the concentration of the endproduct of the metabolic pathway of which the enzyme is a part. A major difficulty with this theory is that there is no obvious relationship between the periodicity of the negative feedback loop, which is determined by the kinetics of synthesis and degradation of the individual components of the feedback loop, and the periodicity of the cell cycle, which is determined by overall net synthetic rates of cellular macromolecules. Why should the period of oscillation of a repressible gene transcription system be close to the interdivision time of a population of growing cells? In this paper, I show that the relationship may be coincidental: the two fundamental periods are close to each other because they are both close to the mass-doubling time of the cell culture. That the mean interdivision time must be close to the mass-doubling time is a consequence of "balanced" growth: there is a stable size distribution of cells in a growing culture. That the period of oscillation of the negative feedback loop is also close to the mass-doubling time is shown to be a consequence of the large, nearly constant demand for endproduct and the assumed stability of the enzyme. The period of oscillation is largely attributable to the slow dilution of the stable enzyme by cell growth. For reasonable values of the parameters describing the gene-control system, I show that the enzyme must be diluted by a factor of two (approximately), that is, by the growth accomplished by one mass-doubling (nearly).
在细胞培养的指数增长阶段，一些酶会周期性地合成。在同步培养中，所有细胞或多或少同步进行DNA合成和分裂，酶合成的爆发在每个细胞的每个分裂周期中也同步发生。然而，存在许多有趣的情况，即周期性酶合成在没有同步DNA复制或细胞分裂的情况下仍会持续。在异步培养中周期性酶合成的所有情况中，酶合成爆发之间的时间间隔，虽然不再与细胞周期时间相同，但仍然接近正在生长、进行复制的细胞的分裂间隔时间。振荡抑制理论试图通过该酶所属代谢途径终产物浓度的周期性波动导致的基因转录周期性抑制来解释这一现象。该理论的一个主要困难在于，由反馈环各组分合成和降解动力学决定的负反馈环的周期性，与由细胞大分子总体净合成速率决定的细胞周期的周期性之间没有明显的关系。为什么可抑制基因转录系统的振荡周期会接近一群生长细胞的分裂间隔时间呢？在本文中,我指出这种关系可能是巧合：这两个基本周期彼此接近是因为它们都接近细胞培养物的质量加倍时间。平均分裂间隔时间必须接近质量加倍时间是“平衡”生长的结果：在生长的培养物中细胞存在稳定的大小分布。负反馈环的振荡周期也接近质量加倍时间被证明是终产物大量且近乎恒定的需求以及假定的酶稳定性的结果。振荡周期很大程度上归因于细胞生长对稳定酶的缓慢稀释。对于描述基因控制系统的参数的合理值，我表明酶必须被稀释两倍（大约），也就是说，通过一次质量加倍（近乎）所完成的生长来实现。
