Henrick Kacser

Dr. Henrik Kacser (1918-1995) was a physical chemist.

Additional recommended knowledge

What is the Sensitivity of my Balance?

How to quickly check pipettes?

Recognize and detect the effects of electrostatic charges on your balance

Early life and education

Henrik was born in Romania of Austro-Hungarian parents who later moved to Berlin where Henrik went to school. Before the World War II, he went to Queen's University, Belfast to study chemistry, and specialized in physical chemistry as a postgraduate student. In 1952 he moved to the University of Edinburgh as a Nuffield Fellow under a scheme to introduce physical scientists into biology. He took the Diploma of Animal Genetics course and was invited to stay on in the Department of Genetics, becoming a lecturer in 1955. Henrik's achievement has been recognized by his election to the Royal Society of Edinburgh in 1990, by an Honorary Doctorate of the University of Bordeaux II in 1993.

Research

The control of flux

The control of flux (Kacser & Burns, 1973) ^[1] was a landmark paper for both Kacser and Jim Burns describing how the rates of metabolic pathways were affected by changes in the amounts or activities of pathway enzymes. In it they show that the expectation that a metabolic pathway will be controlled by a single pacemaker reaction is a fallacy, and most of the experimental criteria used in the supposed identification of such steps are misleading. Instead, varying amounts of control can be distributed over the enzymes of the pathway, but this is a property of the metabolic system as a whole and cannot be predicted from the characteristics of the enzymes in isolation.

The molecular basis of dominance

The molecular basis of dominance (Kacser & Burns, 1981) ^[2] is the companion paper to "The control of flux" and reveals the full meaning of its footnote "the implication of this for the problem of dominance and its evolution will be dealt with in a separate publication". The connection was that if the flux–enzyme relationship is quasi-hyperbolic, and if, for most enzymes, the wild-type diploid level of enzyme activity occurs where the curve is levelling out, then a heterozygote of the wild-type with a null mutant will have half the enzyme activity but will not exhibit a noticeably reduced flux. Therefore the wild type appears dominant and the mutant recessive because of the system characteristics of a metabolic pathway.

Recent papers

Recent papers include:

• Responses of metabolic systems to large changes in enzyme activities and effectors: 1. The linear treatment of unbranched chains (Small & Kacser, 1993a) ^[3]

• Responses of metabolic systems to large changes in enzyme activities and effectors: 2. The linear treatment of branched chains (Small & Kacser, 1993b) ^[4]

• A universal method for achieving increases in metabolite production (Kacser & Acerenza, 1993) ^[5]

These recent 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.

Henrik continued his research after his official retirement in 1988 right up until his death in 1995. At the time of his death, Henrik still ran an active laboratory, had two large grants supporting his work and continued to produce original scientific ideas.

References