A circulatory model for human metabolism

Abstract

We describe a new circulatory model for the analysis of human metabolic data compatible with the limited information obtainable in clinical studies when only a few metabolites are observed. The model makes no assumptions about intermediary metabolites, which may not be known, the existence of compartments or the size of these compartments. Only observed data are employed. While for a single substance the model provides no new format, the description of the quantitative relationship between two or more substances is unambiguous and precise, and allows considerably more insight than by previous methods. Via the model, direct entry rates into plasma metabolites, the direct departure rates and the conversion rate between two substances, both for first conversion and repetitive conversions, can be established. Specification of the data needed to determine these kinetic relationships is given. For the glucose-alanine system peculiarities present which may require extra steps in data analysis are described. The randomness generated by turbulent mixing in the heart gives the underlying theory a probabilistic character, and much of the methodology has its origins there. The randomness is nullified by the law of large numbers, but the mathematical structure remains.