CONTRIBUTIONS OF THE WOOD-WERKMAN REACTION TO THE TRICARBOXYLIC ACID CYCLE

Abstract

The TCA cycle in vico can be regarded as a kind of reaction system of open catalytic cycle in view of the fact that the members of cycle are interconvertible with some amino acids. In a previous paper, the author have developed a general theory of a metabolizing system with cyclic process, and now it is applied to a reaction system of open catalytic cycle with special reference to the TCA cycle. It is shown that the interconversion between the members of TCA cycle and some amino acids is compensated by the reversible Wood-Werkman reaction, by means of which the metabolic flow of TCA cycle can be maintained in the stationary state.
We have thus two kinds of the stationary states of the TCA cycle either accompanied or not by the stationary anabolic flow of pyruvic acid to some amino acids through the Wood-Werkman reaction. In contrast with the latter flow, the flow of TCA cycle can be called the catabolic floss of pyruvic acid to carbon dioxide and water.
When pyruvic acid is constantly supplied into the system the two flows interfere complementarily with each other. The equations are derived which represent the mutual interference of the two stationary flows. The inter-ference depends on the resistance to the supply of pyruvic acid into the system. When this resistance is much larger than all other ones, the most intensive interference appears and consequently amino acids instead of pyruvic acid are completely oxidized through the operation of the TCA cycle accompanied by the Wood-Werkman reaction.
When the metabolic flow of TCA cycle shifts from a stationary state without the flow of Wood-Werkman reaction to another one accom-panied by the latter flow, the former flow and hence the energy captured in the cycle decrease in proportion to the latter flow, while they increase provided that the latter flow goes in the opposite direction.
The present theory thus leads to the following conclusions: 1) The TCA cycle may be able to operate effectively as a “metabolic buffer” in cooperation with the Wood-Werkman reaction. 2) The TCA cycle may be regarded as an “energy capturing system” controlled by the Wood-Werkman reaction.
The author expresses his sincere appreciation to Prof. K. Oomori and Ass. Prof. G. T omit a of this laboratory for their advice and encouragement, and to Prof. S. Akabori of Osaka University for his interest and encouragement in the work. Grateful acknowledgement is made to Prof. M. Sugita of Hitotsubashi University for his repeated inspection of the manuscript and many valuable advices. The author has been greatly encouraged by his constant interest and helpful discussions.