PT  - JOURNAL ARTICLE
AU  - Yamagishi, Jumpei F.
AU  - Hatakeyama, Tetsuhiro S.
TI  - Microeconomics of metabolism: Overflow metabolism as Giffen behavior
AID  - 10.1101/613166
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 613166
4099  - http://biorxiv.org/content/early/2019/04/18/613166.short
4100  - http://biorxiv.org/content/early/2019/04/18/613166.full
AB  - Living organisms optimize their survivability through evolutionary processes. In particular, intracellular metabolic systems are rationally regulated to maximize the cellular growth rate. Correspondingly, the field of microeconomics investigates the behavior of individuals assumed to act rationally to maximize their utility. Therefore, microeconomics can be applied to analyze the metabolic strategies of cells. Toward this end, we developed a microeconomics-based theory of cellular metabolism by precisely mapping the regulation of metabolic systems onto the theory of consumer choice in microeconomics. As a representative example, we focus on overflow metabolism, a seemingly wasteful strategy in which cells utilize fermentation instead of the more energetically efficient respiration (so-called Warburg effect in cancer). To resolve this apparent contradiction, we formulate overflow metabolism as an optimization problem of the allocation of carbon fluxes under the guidance of microeconomic theory. Accordingly, we demonstrate that over-flow metabolism corresponds to Giffen behavior in economics, the strange consumer behavior by which greater amounts of goods are consumed as their price increases. We reveal the general conditions required for both overflow metabolism and Giffen goods: trade-off and complementarity, i.e., the impossibility of substitution for different goods, among multiple objectives. Based on the correspondence with Giffen behavior, a counterintuitive response of metabolism against the leakage and degradation of intermediate metabolites, which corresponds to the change in the price of a consumer good, is predicted. Over-all, this demonstration highlights that application of microeconomics to metabolic systems will offer new predictions and potentially new paradigms for both biology and economics.