Henrik Kacser
Encyclopedia
Henrik Kacser was an influential biochemist
and geneticist
. Henrik's achievements have 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.
in 1918 of Austro-Hungarian parents who later moved to Berlin
where Henrik went to school. Before the World War II
, he move to Belfast
, Northern Ireland, where he did his undergraduate and postgraduate work at the Queen's University of Belfast
. There he studied chemistry
, specializing in physical chemistry
as a postgraduate student. He went to Edinburgh in 1952 as a Nuttfield Fellow under a scheme to introduce physical scientists into biology
. This was to become the start of his work as a geneticist/biochemist. He got the Diploma of Animal Genetics, and in 1955 he became appointed lecturer in the department of Genetics at the University of Edinburgh
.
and very little on genetics
. His work falls into four distinct categories: 1. building a foundation in physical chemistry; 2. development of metabolic control analysis; 3. consolidation and 4. expansion. Only in the third phase of his career his expertise in genetics came to light when he set out to find experimental models to demonstrate the correctness of his paper on metabolic control analysis
.
s (See Metabolic Control Analysis
). 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.
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.
, 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:
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.
, had two large grants supporting his work and continued to produce original scientific ideas. He was elected to the Fellowship of The Royal Society of Edinburgh
in 1990 and in 1993 he received an honorary doctorate from the University of Bordeaux
.
Biochemist
Biochemists are scientists who are trained in biochemistry. Typical biochemists study chemical processes and chemical transformations in living organisms. The prefix of "bio" in "biochemist" can be understood as a fusion of "biological chemist."-Role:...
and geneticist
Geneticist
A geneticist is a biologist who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a researcher or lecturer. Some geneticists perform experiments and analyze data to interpret the inheritance of skills. A geneticist is also a Consultant or...
. Henrik's achievements have been recognized by his election to the Royal Society of Edinburgh
Royal Society of Edinburgh
The Royal Society of Edinburgh is Scotland's national academy of science and letters. It is a registered charity, operating on a wholly independent and non-party-political basis and providing public benefit throughout Scotland...
in 1990, by an Honorary Doctorate of the University of Bordeaux II
Victor Segalen Bordeaux 2 University
Université Victor Segalen Bordeaux 2 is the medicine and life sciences center in the University of Bordeaux system, under the Academy of Bordeaux....
in 1993.
Early life
Henrik (or Henrick) Kacser was born in RomaniaRomania
Romania is a country located at the crossroads of Central and Southeastern Europe, on the Lower Danube, within and outside the Carpathian arch, bordering on the Black Sea...
in 1918 of Austro-Hungarian parents who later moved to Berlin
Berlin
Berlin is the capital city of Germany and is one of the 16 states of Germany. With a population of 3.45 million people, Berlin is Germany's largest city. It is the second most populous city proper and the seventh most populous urban area in the European Union...
where Henrik went to school. Before the World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
, he move to Belfast
Belfast
Belfast is the capital of and largest city in Northern Ireland. By population, it is the 14th biggest city in the United Kingdom and second biggest on the island of Ireland . It is the seat of the devolved government and legislative Northern Ireland Assembly...
, Northern Ireland, where he did his undergraduate and postgraduate work at the Queen's University of Belfast
Queen's University of Belfast
Queen's University Belfast is a public research university in Belfast, Northern Ireland. The university's official title, per its charter, is the Queen's University of Belfast. It is often referred to simply as Queen's, or by the abbreviation QUB...
. There he studied chemistry
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....
, specializing in physical chemistry
Physical chemistry
Physical chemistry is the study of macroscopic, atomic, subatomic, and particulate phenomena in chemical systems in terms of physical laws and concepts...
as a postgraduate student. He went to Edinburgh in 1952 as a Nuttfield Fellow under a scheme to introduce physical scientists into biology
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...
. This was to become the start of his work as a geneticist/biochemist. He got the Diploma of Animal Genetics, and in 1955 he became appointed lecturer in the department of Genetics at the University of Edinburgh
University of Edinburgh
The University of Edinburgh, founded in 1583, is a public research university located in Edinburgh, the capital of Scotland, and a UNESCO World Heritage Site. The university is deeply embedded in the fabric of the city, with many of the buildings in the historic Old Town belonging to the university...
.
Areas of research
In most of his research his original training physical chemistry is quite evident as he focused mainly on the physical/chemical aspects of biology. Much of his early work includes work on practical chemistry, kinetics of enzyme reactionsEnzyme kinetics
Enzyme kinetics is the study of the chemical reactions that are catalysed by enzymes. In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction investigated...
and very little on genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
. His work falls into four distinct categories: 1. building a foundation in physical chemistry; 2. development of metabolic control analysis; 3. consolidation and 4. expansion. Only in the third phase of his career his expertise in genetics came to light when he set out to find experimental models to demonstrate the correctness of his paper on metabolic control analysis
Metabolic control analysis
Metabolic control analysis is a mathematical framework for describingmetabolic, signaling and genetic pathways. MCA quantifies how variables,such as fluxes and species concentrations, depend on network parameters....
.
The control of flux
The control of flux (Kacser & Burns, 1973) 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 enzymeEnzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s (See Metabolic Control Analysis
Metabolic control analysis
Metabolic control analysis is a mathematical framework for describingmetabolic, signaling and genetic pathways. MCA quantifies how variables,such as fluxes and species concentrations, depend on network parameters....
). 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) 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 mutantMutant
In biology and especially genetics, a mutant is an individual, organism, or new genetic character, arising or resulting from an instance of mutation, which is a base-pair sequence change within the DNA of a gene or chromosome of an organism resulting in the creation of a new character or trait not...
will have half the enzyme activity but will not exhibit a noticeably reduced flux
Flux
In the various subfields of physics, there exist two common usages of the term flux, both with rigorous mathematical frameworks.* In the study of transport phenomena , flux is defined as flow per unit area, where flow is the movement of some quantity per time...
. Therefore the wild type appears dominant and the mutant recessive because of the system characteristics of a metabolic pathway.
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 evolutionMolecular evolution
Molecular evolution is in part a process of evolution at the scale of DNA, RNA, and proteins. Molecular evolution emerged as a scientific field in the 1960s as researchers from molecular biology, evolutionary biology and population genetics sought to understand recent discoveries on the structure...
, and to show how metabolic control analysis could be applied to problems in medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
and biotechnology
Biotechnology
Biotechnology is a field of applied biology that involves the use of living organisms and bioprocesses in engineering, technology, medicine and other fields requiring bioproducts. Biotechnology also utilizes these products for manufacturing purpose...
. Another paper published in 1984 showed how the idea of evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
by natural selection
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....
could be applied in a constructive way to provide models for the evolution of enzyme catalysis
Enzyme catalysis
Enzyme catalysis is the catalysis of chemical reactions by specialized proteins known as enzymes. Catalysis of biochemical reactions in the cell is vital due to the very low reaction rates of the uncatalysed reactions....
.
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
Amsterdam
Amsterdam is the largest city and the capital of the Netherlands. The current position of Amsterdam as capital city of the Kingdom of the Netherlands is governed by the constitution of August 24, 1815 and its successors. Amsterdam has a population of 783,364 within city limits, an urban population...
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
Tom Rapoport
Tom Abraham Rapoport is a German-American cell biologist who studies protein transport in cells.He has been a professor at the Harvard Medical School since 1995, and an HHMI investigator since 1997...
in Berlin
Berlin
Berlin is the capital city of Germany and is one of the 16 states of Germany. With a population of 3.45 million people, Berlin is Germany's largest city. It is the second most populous city proper and the seventh most populous urban area in the European Union...
were compatible, a common terminology and set of symbols was agreed for the new field of Metabolic Control Analysis.
Later life
Upon retirement from lecturing in 1988 he became a Fellow of the University of Edinburgh. Kacser was an active geneticist/biochemist right up until his death. At the time of his death, Henrik still ran an active laboratoryLaboratory
A laboratory is a facility that provides controlled conditions in which scientific research, experiments, and measurement may be performed. The title of laboratory is also used for certain other facilities where the processes or equipment used are similar to those in scientific laboratories...
, had two large grants supporting his work and continued to produce original scientific ideas. He was elected to the Fellowship of The Royal Society of Edinburgh
Royal Society of Edinburgh
The Royal Society of Edinburgh is Scotland's national academy of science and letters. It is a registered charity, operating on a wholly independent and non-party-political basis and providing public benefit throughout Scotland...
in 1990 and in 1993 he received an honorary doctorate from the University of Bordeaux
University of Bordeaux
University of Bordeaux is an association of higher education institutions in and around Bordeaux, France. Its current incarnation was established 21 March 2007. The group is the largest system of higher education schools in southwestern France. It is part of the Academy of Bordeaux.There are seven...
.
External links
- Obituary, Royal Society of Edinburgh
- In memory of Henrik Kacser: Special issue of the Journal of Theoretical Biology.
- Annotated Bibliography of Henrik Kacser