Hans Westerhoff

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Hans Westerhoff
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Hans Westerhoff in 2014
Born
Hans Victor Westerhoff

(1953-01-14) 14 January 1953 (age 70) [1]
Amsterdam, The Netherlands
Alma mater University of Amsterdam (PhD)
Scientific career
FieldsBiological thermodynamics, Systems biology [2]
Institutions
Thesis Mosaic non-equilibrium thermodynamics and (the control of) biological free-energy transduction  (1983)
Doctoral advisor Karel van Dam [1] [3]
Website www.manchester.ac.uk/research/hans.westerhoff

Hans Victor Westerhoff (born 14 January 1953 in Amsterdam, Netherlands) [1] is a Dutch biologist and biochemist who is professor of synthetic systems biology at the University of Amsterdam [4] and AstraZeneca professor of systems biology at the University of Manchester. [2] Currently he is a Chair of AstraZeneca and a director of the Manchester Centre for Integrative Systems Biology. [5] [6]

Contents

Career

Westerhoff was educated at the University of Amsterdam where he was awarded a PhD in 1983 for investigations of non-equilibrium thermodynamics and the control of biological thermodynamics supervised by Karel van Dam. [1] In 1996 he succeeded Ad Stouthamer as professor of microbiology at the Vrije Universiteit Amsterdam. [7]

Research

At the beginning of his career Westerhoff worked in the area of non-equilibrium thermodynamics in relation to biological energy transduction. [8] [9] His work on this topic led to a book written with Karel Van Dam. [10]

After being a coauthor of one of the first experimental papers to stimulate interest in metabolic control analysis [11] and participating in the group that proposed a harmonized terminology, [12] Westerhoff moved progressively towards working on multi-enzyme systems as his major activity, starting with an analysis of the effect of enzyme activity on metabolite concentrations. [13] He published many papers in this area, of which one may note an analysis of the control of regulatory cascades, [14] analysqis of glycolytic oscilations in yeast, [15] and showing that the in vivo behaviour of Trypanosoma brucei agreed with the kinetic properties of the glycolytic enzymes. [16]

Westerhoff and colleagues discovered magainin in the African clawed frog which helps it fight against bacteria. [17] In December 1996 he and his group discovered a nitric-oxide reductase of Paracoccus denitrificans . [18]

In conjunction with many other workers Westerhoff used a community approach to construct a consensus yeast metabolic network [19] and subsequently applied the same approach to human metabolism. [20]

Related Research Articles

<span class="mw-page-title-main">Glycolysis</span> Catabolic pathway

Glycolysis is the metabolic pathway that converts glucose into pyruvate, and in most organisms, occurs in the liquid part of cells, the cytosol. The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes.

<span class="mw-page-title-main">Metabolism</span> Set of chemical reactions in organisms

Metabolism is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the conversion of food to building blocks for proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of metabolic wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments. The word metabolism can also refer to the sum of all chemical reactions that occur in living organisms, including digestion and the transportation of substances into and between different cells, in which case the above described set of reactions within the cells is called intermediary metabolism.

<span class="mw-page-title-main">Mannose</span> Chemical compound

Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation are associated with mutations in enzymes involved in mannose metabolism.

<span class="mw-page-title-main">Fructose 1,6-bisphosphatase</span> Class of enzymes

The enzyme fructose bisphosphatase (EC 3.1.3.11; systematic name D-fructose-1,6-bisphosphate 1-phosphohydrolase) catalyses the conversion of fructose-1,6-bisphosphate to fructose 6-phosphate in gluconeogenesis and the Calvin cycle, which are both anabolic pathways:

<span class="mw-page-title-main">Phosphofructokinase 1</span> Class of enzymes

Phosphofructokinase-1 (PFK-1) is one of the most important regulatory enzymes of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors. PFK-1 catalyzes the important "committed" step of glycolysis, the conversion of fructose 6-phosphate and ATP to fructose 1,6-bisphosphate and ADP. Glycolysis is the foundation for respiration, both anaerobic and aerobic. Because phosphofructokinase (PFK) catalyzes the ATP-dependent phosphorylation to convert fructose-6-phosphate into fructose 1,6-bisphosphate and ADP, it is one of the key regulatory steps of glycolysis. PFK is able to regulate glycolysis through allosteric inhibition, and in this way, the cell can increase or decrease the rate of glycolysis in response to the cell's energy requirements. For example, a high ratio of ATP to ADP will inhibit PFK and glycolysis. The key difference between the regulation of PFK in eukaryotes and prokaryotes is that in eukaryotes PFK is activated by fructose 2,6-bisphosphate. The purpose of fructose 2,6-bisphosphate is to supersede ATP inhibition, thus allowing eukaryotes to have greater sensitivity to regulation by hormones like glucagon and insulin.

<span class="mw-page-title-main">Pyruvate kinase</span> Class of enzymes

Pyruvate kinase is the enzyme involved in the last step of glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), yielding one molecule of pyruvate and one molecule of ATP. Pyruvate kinase was inappropriately named before it was recognized that it did not directly catalyze phosphorylation of pyruvate, which does not occur under physiological conditions. Pyruvate kinase is present in four distinct, tissue-specific isozymes in animals, each consisting of particular kinetic properties necessary to accommodate the variations in metabolic requirements of diverse tissues.

<span class="mw-page-title-main">Adenylate kinase</span> Class of enzymes

Adenylate kinase is a phosphotransferase enzyme that catalyzes the interconversion of the various adenosine phosphates. By constantly monitoring phosphate nucleotide levels inside the cell, ADK plays an important role in cellular energy homeostasis.

Henrik Kacser FRSE was a Romanian-born biochemist and geneticist who worked in Britain in the 20th century. Kacser's achievements have been recognised by his election to the Royal Society of Edinburgh in 1990, by an honorary doctorate of the University of Bordeaux II in 1993.

<span class="mw-page-title-main">Phosphofructokinase 2</span> Class of enzymes

Phosphofructokinase-2 (6-phosphofructo-2-kinase, PFK-2) or fructose bisphosphatase-2 (FBPase-2), is an enzyme indirectly responsible for regulating the rates of glycolysis and gluconeogenesis in cells. It catalyzes formation and degradation of a significant allosteric regulator, fructose-2,6-bisphosphate (Fru-2,6-P2) from substrate fructose-6-phosphate. Fru-2,6-P2 contributes to the rate-determining step of glycolysis as it activates enzyme phosphofructokinase 1 in the glycolysis pathway, and inhibits fructose-1,6-bisphosphatase 1 in gluconeogenesis. Since Fru-2,6-P2 differentially regulates glycolysis and gluconeogenesis, it can act as a key signal to switch between the opposing pathways. Because PFK-2 produces Fru-2,6-P2 in response to hormonal signaling, metabolism can be more sensitively and efficiently controlled to align with the organism's glycolytic needs. This enzyme participates in fructose and mannose metabolism. The enzyme is important in the regulation of hepatic carbohydrate metabolism and is found in greatest quantities in the liver, kidney and heart. In mammals, several genes often encode different isoforms, each of which differs in its tissue distribution and enzymatic activity. The family described here bears a resemblance to the ATP-driven phospho-fructokinases, however, they share little sequence similarity, although a few residues seem key to their interaction with fructose 6-phosphate.

<span class="mw-page-title-main">Glyceraldehyde 3-phosphate dehydrogenase</span> Enzyme of the glycolysis metabolic pathway

Glyceraldehyde 3-phosphate dehydrogenase is an enzyme of about 37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. In addition to this long established metabolic function, GAPDH has recently been implicated in several non-metabolic processes, including transcription activation, initiation of apoptosis, ER to Golgi vesicle shuttling, and fast axonal, or axoplasmic transport. In sperm, a testis-specific isoenzyme GAPDHS is expressed.

<span class="mw-page-title-main">UTP—glucose-1-phosphate uridylyltransferase</span> Class of enzymes

UTP—glucose-1-phosphate uridylyltransferase also known as glucose-1-phosphate uridylyltransferase is an enzyme involved in carbohydrate metabolism. It synthesizes UDP-glucose from glucose-1-phosphate and UTP; i.e.,

<span class="mw-page-title-main">Phosphofructokinase</span> Enzyme in glycolysis

Phosphofructokinase (PFK) is a kinase enzyme that phosphorylates fructose 6-phosphate in glycolysis.

<span class="mw-page-title-main">MAP3K1</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is a signal transduction enzyme that in humans is encoded by the autosomal MAP3K1 gene.

<span class="mw-page-title-main">PKM2</span> Protein-coding gene in the species Homo sapiens

Pyruvate kinase isozymes M1/M2 (PKM1/M2), also known as pyruvate kinase muscle isozyme (PKM), pyruvate kinase type K, cytosolic thyroid hormone-binding protein (CTHBP), thyroid hormone-binding protein 1 (THBP1), or opa-interacting protein 3 (OIP3), is an enzyme that in humans is encoded by the PKM2 gene.

<span class="mw-page-title-main">ADP/ATP translocase 4</span> Protein-coding gene in the species Homo sapiens

ADP/ATP translocase 4 (ANT4) is an enzyme that in humans is encoded by the SLC25A31 gene on chromosome 4. This enzyme inhibits apoptosis by catalyzing ADP/ATP exchange across the mitochondrial membranes and regulating membrane potential. In particular, ANT4 is essential to spermatogenesis, as it imports ATP into sperm mitochondria to support their development and survival. Outside this role, the SLC25AC31 gene has not been implicated in any human disease.

Metabolite channeling is the passing of the intermediary metabolic product of one enzyme directly to another enzyme or active site without its release into solution. When several consecutive enzymes of a metabolic pathway channel substrates between themselves, this is called a metabolon. Channeling can make a metabolic pathway more rapid and efficient than it would be if the enzymes were randomly distributed in the cytosol, or prevent the release of unstable intermediates. It can also protect an intermediate from being consumed by competing reactions catalyzed by other enzymes.

<span class="mw-page-title-main">Douglas Kell</span> British biochemist

Chief Sci

Stephen George Oliver is an Emeritus Professor in the Department of Biochemistry at the University of Cambridge, and a Fellow of Wolfson College, Cambridge.

<span class="mw-page-title-main">Steve Pettifer</span>

Stephen Robert Pettifer is a Professor in the Department of Computer Science at the University of Manchester in England.

Jan-Hendrik HofmeyrFRSSAf is one of the leaders in the field of metabolic control analysis and the quantitative analysis of metabolic regulation.

References

  1. 1 2 3 4 Prof. dr. H.V. Westerhoff, 1953- at the University of Amsterdam Album Academicum website
  2. 1 2 "Hans Westerhoff". Google Scholar. Archived from the original on December 18, 2013. Retrieved December 9, 2013.
  3. ↑ Academic Tree: Karel van Dam, Amsterdam
  4. ↑ "Prof. Dr. H.V. (Hans) Westerhoff". University of Amsterdam. Archived from the original on December 12, 2013. Retrieved December 9, 2013.
  5. ↑ "Professor Hans Westerhoff". University of Manchester. Archived from the original on December 15, 2013. Retrieved December 9, 2013.
  6. ↑ Hans Westerhoff's publications indexed by the Scopus bibliographic database. (subscription required)
  7. ↑ Martine Zuidweg (11 June 1997). "De confrontatie" (in Dutch). Trouw. Retrieved 19 July 2020.
  8. ↑ Van der Meer, R; Westerhoff, H V; Van Dam, K (1980). "Linear relation between rate and thermodynamic force in enzyme-catalyzed reactions". Biochim. Biophys. Acta. 591 (2): 488–493. doi:10.1016/0005-2728(80)90179-6. PMID   7397133.
  9. ↑ Westerhoff, H V; Hellingwerf, K J; Arents, J C; Scholte, B J; Van Dam, K (1981). "Mosaic non-equilibrium thermodynamics describes biological energy transduction". Proc. Natl. Acad. Sci. USA. 78 (1): 3554–3558. Bibcode:1981PNAS...78.3554W. doi: 10.1073/pnas.78.6.3554 . PMC   319608 . PMID   6267598.
  10. ↑ Westerhoff, H V; Van Dam, K (1987). Thermodynamics and Control of Biological Free-Energy Transduction. Elsevier. ISBN   978-0-444-80783-0.
  11. ↑ Groen, AK; Wanders, RJA; Westerhoff, HV; van de Meer, R; Tager, JM (1982). "Quantification of the contribution of various steps to the control of mitochondrial respiration". Journal of Biological Chemistry. 257 (6): 2754–2757. doi: 10.1016/S0021-9258(19)81026-8 . PMID   7061448.
  12. ↑ Burns, J.A.; Cornish-Bowden, A.; Groen, A.K.; Heinrich, R.; Kacser, H.; Porteous, J.W.; Rapoport, S.M.; Rapoport, T.A.; Stucki, J.W.; Tager, J.M.; Wanders, R.J.A.; Westerhoff, H.V. (1985). "Control analysis of metabolic systems". Trends Biochem. Sci. 10: 16. doi:10.1016/0968-0004(85)90008-8.
  13. ↑ Westerhoff, Hans V.; Chen, Yi-Der (1984). "How do enzyme activities control metabolite concentrations? An additional theorem in the theory of metabolic control". Eur. J. Biochem. 142 (2): 425–430. doi: 10.1111/j.1432-1033.1984.tb08304.x . PMID   6745283.
  14. ↑ Kahn, D; Westerhoff, H.V. (1991). "Control theory of regulatory cascades". J. Theor. Biol. 153 (2): 255–285. Bibcode:1991JThBi.153..255K. doi:10.1016/S0022-5193(05)80426-6. PMID   1686290.
  15. ↑ Bier, M; Bakker, B. M.; Westerhoff, H. V. (2000). "How yeast cells synchronize their glycolytic oscillations: A perturbation analytic treatment". Biophys. J. 78 (3): 1087–93. Bibcode:2000BpJ....78.1087B. doi:10.1016/S0006-3495(00)76667-7. PMC   1300712 . PMID   10692299.
  16. ↑ Bakker, B M; Michels, P A M; Opperdoes, F R; Westerhoff, H V (1997). "Glycolysis in bloodstream form Trypanosoma brucei can be understood in terms of the kinetics of the glycolytic enzymes". J. Biol. Chem. 272 (6): 3207–3215. doi: 10.1074/jbc.272.6.3207 . PMID   9013556.
  17. ↑ Westerhoff, H. V.; Zasloff, M.; Rosner, J. L.; Hendler, R. W.; Waal, A.; Gomes, A. V.; Jongsma, A. P. M.; Riethorst, A.; Juretic, D. (1995). "Functional Synergism of the Magainins PGLa and Magainin-2 in Escherichia coli, Tumor Cells and Liposomes" (PDF). European Journal of Biochemistry. 228 (2): 257–64. doi:10.1111/j.1432-1033.1995.0257n.x. PMID   7705337.
  18. ↑ Boer, A. P. N.; Oost, J.; Reijnders, W. N. M.; Westerhoff, H. V.; Stouthamer, A. H.; Spanning, R. J. M. (1996). "Mutational Analysis of the nor Gene Cluster which Encodes Nitric-Oxide Reductase from Paracoccus denitrificans". European Journal of Biochemistry. 242 (3): 592–600. doi: 10.1111/j.1432-1033.1996.0592r.x . PMID   9022686.
  19. ↑ Herrgård, M. J.; Swainston, N.; Dobson, P.; Dunn, W. B.; Arga, K. Y. I.; Arvas, M.; Blüthgen, N.; Borger, S.; Costenoble, R.; Heinemann, M.; Hucka, M.; Le Novère, N.; Li, P.; Liebermeister, W.; Mo, M. L.; Oliveira, A. P.; Petranovic, D.; Pettifer, S.; Simeonidis, E; Smallbone, K; Spasic, I; Weichart, D.; Brent, R.; Broomhead, D. S.; Westerhoff, H. V.; Kirdar, B. L.; Penttilä, M.; Klipp, E.; Palsson, B. Ø.; Sauer, U.; Oliver, S. G.; Mendes, P.; Nielsen, J.; Kell, D.B. (2008). "A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology". Nature Biotechnology. 26 (10): 1155–1160. doi:10.1038/nbt1492. PMC   4018421 . PMID   18846089.
  20. ↑ Thiele, I; Swainston, N; Fleming, R M T; Hoppe, A; Sahoo, S; Aurich, M K; Haraldsdottir, H; Mo, M L; Rolfsson, O; Stobbe, M D; Thorleifsson, S G; Agren, R; Bolling, C; Bordel, S; Chavali, A K; Dobson, P; Dunn, W B; Endler, L; Hala, D; Hucka, M; Hull, D; Jameson, D; Jonsson, J J; Juty, N; Keating, S; Nookaew, I; Le Novère, N; Malys, N; Mazein, A; Papin, J A; Price, N D; Selkov, E; Sigurdsson, M I; Simeonidis, E; Sonnenschein, N; Smallbone, K; Sorokin, A; van Beek, J H G M; Weichart, D; Goryanin, I; Nielsen, J; Westerhoff, H V; Kell, D B; Mendes, P; Palsson, B O (2013). "A community-driven global reconstruction of human metabolism". Nature Biotechnology. 31 (5): 419–425. doi:10.1038/nbt.2488. PMC   3856361 . PMID   23455439.
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