Shestopaloff Yuri K
Segmentsoft Inc., Toronto, Ontario, Canada.
PLoS One. 2014 Jun 18;9(6):e99836. doi: 10.1371/journal.pone.0099836. eCollection 2014.
We propose a method for finding metabolic parameters of cells, organs and whole organisms, which is based on the earlier discovered general growth law. Based on the obtained results and analysis of available biological models, we propose a general framework for modeling biological phenomena and discuss how it can be used in Virtual Liver Network project. The foundational idea of the study is that growth of cells, organs, systems and whole organisms, besides biomolecular machinery, is influenced by biophysical mechanisms acting at different scale levels. In particular, the general growth law uniquely defines distribution of nutritional resources between maintenance needs and biomass synthesis at each phase of growth and at each scale level. We exemplify the approach considering metabolic properties of growing human and dog livers and liver transplants. A procedure for verification of obtained results has been introduced too. We found that two examined dogs have high metabolic rates consuming about 0.62 and 1 gram of nutrients per cubic centimeter of liver per day, and verified this using the proposed verification procedure. We also evaluated consumption rate of nutrients in human livers, determining it to be about 0.088 gram of nutrients per cubic centimeter of liver per day for males, and about 0.098 for females. This noticeable difference can be explained by evolutionary development, which required females to have greater liver processing capacity to support pregnancy. We also found how much nutrients go to biomass synthesis and maintenance at each phase of liver and liver transplant growth. Obtained results demonstrate that the proposed approach can be used for finding metabolic characteristics of cells, organs, and whole organisms, which can further serve as important inputs and constraints for many applications in biology (such as protein expression), biotechnology (synthesis of substances), and medicine.
我们提出了一种基于早期发现的一般生长规律来寻找细胞、器官和整个生物体代谢参数的方法。基于所获得的结果以及对现有生物学模型的分析，我们提出了一个用于对生物现象进行建模的通用框架，并讨论了它如何应用于虚拟肝脏网络项目。该研究的基本思想是，细胞、器官、系统和整个生物体的生长，除了生物分子机制外，还受到在不同尺度水平上起作用的生物物理机制的影响。特别是，一般生长规律唯一地定义了在生长的每个阶段和每个尺度水平上，营养资源在维持需求和生物量合成之间的分配。我们以生长中的人类和狗的肝脏以及肝脏移植的代谢特性为例说明了该方法。还引入了一种验证所得结果的程序。我们发现，两只受试狗的代谢率很高，每天每立方厘米肝脏消耗约0.62克和1克营养物质，并使用所提出的验证程序对其进行了验证。我们还评估了人类肝脏中营养物质的消耗率，确定男性为每天每立方厘米肝脏约0.088克营养物质，女性约为0.098克。这种显著差异可以通过进化发展来解释，进化发展要求女性具有更大的肝脏处理能力以支持怀孕。我们还发现了在肝脏和肝脏移植生长的每个阶段，有多少营养物质用于生物量合成和维持。所得结果表明，所提出的方法可用于寻找细胞、器官和整个生物体的代谢特征，这可为生物学（如蛋白质表达）、生物技术（物质合成）和医学中的许多应用提供重要的输入和约束。
