Henrik Kacser - Influential Publications

Influential Publications

Kacser's most important work was published in 1973. Written with J.A. Burns it was called the “Control of Flux” paper. By the mid-1980s the central ideas of metabolic control analysis laid out in this paper were becoming far more widely accepted. Further experimental methods based on the theories laid out in the paper were used to help in the understanding of metabolic regulation and molecular evolution, and to show how metabolic control analysis could be applied to problems in medicine and biotechnology. Another paper published in 1984 showed how the idea of evolution by natural selection could be applied in a constructive way to provide models for the evolution of enzyme catalysis.

Other papers include:

• Responses of metabolic systems to large changes in enzyme activities and effectors: 1. The linear treatment of unbranched chains (Small & Kacser, 1993a)
• Responses of metabolic systems to large changes in enzyme activities and effectors: 2. The linear treatment of branched chains (Small & Kacser, 1993b)
• A universal method for achieving increases in metabolite production (Kacser & Acerenza, 1993)

These papers, in collaboration with Rankin Small and Luis Acerenza, have shown that the prospects for achieving large increases in flux by changing the activity of a single enzyme are poor but a coordinated set of changes, designed by their "Universal Method" could make large changes without catastrophic perturbations of the rest of metabolism.

Biochemical interest in the ideas expressed in "The control of flux" started to grow in the 1980s, particularly with its experimental applications in Amsterdam to oxidative phosphorylation, urea synthesis and gluconeogenesis. At this time, because the theory of Kacser and Burns and the simultaneous but independent work carried out by Reinhart Heinrich and Tom Rapoport in Berlin were compatible, a common terminology and set of symbols was agreed for the new field of Metabolic Control Analysis.