Citric acid cycle as a "one-step" reaction.

One of the most familiar metabolic pathways is the citric acid cycle. This reaction sequence is characterized by intermediates which can be detected in aqueous solution. The recent success in isolating an enzyme cluster with five cycle activities suggests that the cyclic sequence should find a counterpart in a highly organized enzyme system for effective catalysis. In the present article, a new way of looking at this complex reaction sequence is proposed utilizing the hydrophobicity of active sites to define the entrance or exit of substrates as a first or last reaction step. With this view, highly reactive intermediates can be formulated which are able to react in a quasi "one step" mechanism to stable end-products. It is possible to derive the known intermediates of the citric acid cycle by a transition from a proposed hydrophobic catalytic site into the aqueous phase. A variety of biochemical concepts in use ("energy-rich"-bonds, group transfer, substrate-channelling, transporters, etc.) can be understood to be derived from methodology commonly in use. The proposed reaction mechanism demands a specific organization of the proteins forming the enzymatic activity(ies). Isolated and purified enzymes should, in consequence, be seen as isolation products, differing from their functionally organized form in a living cell. In this paper, a new concept is proposed by which a variety of observations and concepts can be unified.