A kinetic model of metabolism essential to differentiation in Dictyostelium discoideum.

those of more complex organisms; (2) the lack of growth and of extensive qualitative changes at the enzyme level; and (3) the availability of the various kinds of information required to fully analyze the "fine-level" control of metabolism: cellular levels of substrates, products, coenzymes, and effectors; enzyme specific activities, affinity constants, etc.; and most importantly, the rates in vivo of critical reactions necessary to differentiation. The data that have now accumulated relevant to the intermediary metabolism of the cellular slime mold have reached a stage of complexity requiring a quantitative dynamic model for further analysis. The range of possible control mechanisms and their interdependence have become so complicated that it is difficult to distinguish cause from effect and random variation from significant change.' The kinetic model to be presented is preliminary and must become more complex and sophisticated as other factors known to be involved are included and as new data become available. However, even in its present simplified form, the model has provided a valuable conceptual framework for thinking in kinetic terms and for understanding some of the complexities of the differentiating cell; it has revealed new relationships and objectives not previously apparent and has made possible specific predictions, which are now being tested in the laboratory. Data Relevant to the Model.-Differentiation in the cellular slime mold can be described as a "closed system" in the sense that the cells are starving and independent of exogenous nutrients; dry weight decreases to about half the original value. Total carbohydrate content, based on the original dry weight, remains fairly constant throughout development.2-4 By the end of the differentiation process, it is possible to account very roughly for the total carbohydrate (anthrone-positive) material (about 14% of the final dry weight) in terms of identifiable compounds. Expressed in glucose equivalents/ml of packed cells (--100 mg dry weight) and as per cent of the original dry weight, these materials