Abstract
Enormous information has been obtained by the exceptional achievements of molecular and cellular biology in last a half century. Accumulation of data at the higher-level biological structures, such as tissues, organs, and individual creatures, gets behind and broadens the context for that obtained the molecular and cellular levels. Under such auspices, a trial to elucidate mesoscopic-macroscopic subjects based on plentiful nanoscopic-microscopic data is of great potential value. We have constructed a mathematical model of ammonia metabolism in hepatic lobule based on a single-hepatocyte model that consists of the biochemical kinetics of enzymes and transporters. The porto-central axis, which is an elemental structure of the lobule, is defined as the systems biological unit of the liver, and is accordingly modeled. A model including both histological structure and position-specific gene expression of major enzymes largely represents the physiological dynamics of the hepatic lobule in nature. In addition, heterogeneous gene expression is suggested to have evolved to optimize the energy efficiency of ammonia detoxification at the macroscopic level, implying that approaches like this may elucidate how properties at the molecular and cellular levels, such as regulated gene expression, modify higher-level phenomena of multicellular tissue, organs, and individuals. [J Physiol Sci. 2007;57 Suppl:S181]
