The 6th Biothermokinetics conference was held in Schrocken, Austria on 20-24=
=20
September 1994.
The organiser of the conference, Dr Erich Gnaiger, produced the proceedings=
=20
of the meeting in time for distribution to the participants (Well done=20
Erich!). There are additional copies available from him, if you contact him=
=20
directly at: Department of Transplant Surgery, Clinical & Interdisciplinary=
=20
Bioenergetics, University Hospital of Innsbruck, Anichstrasse 35, A-6020=20
INNSBRUCK, Austria. FAX: +43 512 504 2605. (No email, unfortunately, as he=
=20
works in a hospital.)
The subjects discussed can be found in the following contents list. In the=
=20
near future, we will atempt to make the text of the proceedings available=20
over the Internet, but it is likely that this will be without diagrams (and=
=20
possibly equations), and pagination will probably be inconsistent with the=
=20
Contents and Index, so the hardcopy will be beter for serious study.
Posted by David Fell, daf at bms.brookes.ac.uk
.......................................................................
CONTENTS
Preface
R. Margreiter. Innsbruck . . . . . . . . . . . . . . . . . 13
Trends in Bioenergetics. An Introduction
E. Gnaiger, F.N. Gellerich. Innsbruck . . . . . . . . . . 14
"German Ideology" as seen by Erwin Schr=94dinger in Letters=20
to Hans Thirring. From Their Correspondence (1946 - 1949)
G. Oberkofler, P. Goller. Innsbruck . . . . . . . . . . . 19
Part 1
What is Negative Entropy?
From World Views to Bioenergetics
Erwin Schr=94dinger's World View. The Role of Physics and=20
Biology in his Philosophical System
J. G=94tschl. Graz . . . . . . . . . . . . . . . . . . . . . 23
Science, Art and Revelation
J. Wagensberg. Barcelona . . . . . . . . . . . . . . . . . 32
Negentropy and Historical Arrow of Time - Thermodynamical and=20
Informational Aspects of the Darwinian Revolution
G.F. Azzone. Padova . . . . . . . . . . . . . . . . . . . 38
Negative Entropy: Another Approach
C.P. Lantos. Buenos Aires . . . . . . . . . . . . . . . . 45
Schr=94dinger's What is Life?: The Biophysical Legacy 50 Years Later
G.R. Welch. New Orleans . . . . . . . . . . . . . . . . . 48
What is (Schr=94dinger's) Negentropy?
M.-W. Ho. London . . . . . . . . . . . . . . . . . . . . . 50
Negative Entropy for Living Systems. Controversy between=20
Nobel Laureates Schr=94dinger, Pauling and Perutz
E. Gnaiger. Innsbruck . . . . . . . . . . . . . . . . . . 62
A Paradigm for Energy Balance in Muscle Function
M.J. Kushmerick. Seattle . . . . . . . . . . . . . . . . . 71
A Controlled Chaotic Attractor Controls Life
D. Lloyd. Cardiff . . . . . . . . . . . . . . . . . . . . 77
Disease as Instability, Error and Entropy
G.F. Azzone. Padova . . . . . . . . . . . . . . . . . . . 81
Part 2
Control and Regulation: Theory, Models, and Experiment
The Macro- and Microworld of Control Theory
B.N. Kholodenko, H.V. Westerhoff, M. Cascante.=20
Moscow, Amsterdam, Barcelona . . . . . . . . . . . . . . . 88
How Should we Quantify Metabolic Regulation?=20
J.-H.S. Hofmeyr, A. Cornish-Bowden. Stellenbosch, Marseille91
Control and Regulation: The Best of Both Worlds
H.V. Westerhoff, P.R. Jensen, J.M. Rohwer, B.N. Kholodenko.=20
Amsterdam, Lyngby, Moscow . . . . . . . . . . . . . . . . 95
Evolutionary Optimization of Enzymes on the Basis of=20
Kinetic and Thermodynamic Principles
R. Heinrich, E. Klipp, A. Stephani, T. Wilhelm, Berlin . . 99
Detecting Elementary Modes of Functioning in Metabolic Networks
S. Schuster, C. Hilgetag, D.A. Fell. Berlin, Oxford . . .103
Modular Control and Regulation. A.A. van der Gugten, H.V. Westerhoff.=20
Amsterdam106
Regulation of hierarchically organized metabolic systems.=20
J.-H.S. Hofmeyr, H.V. Westerhoff. Stellenbosch, Amsterdam 106
Determining Elasticities from Measured Fluxes and Metabolite Concentrations:=
=20
An Inverse Problem. C. Giersch. Darmstadt . . . . . . . .107
Measuring Elasticities by Means of the Multiple Modulation Method.=20
C. Giersch, L. Bartosch, S. Lenz. Darmstadt . . . . . . .108
Co-Response Analysis: A New Strategy for Experimental Metabolic Control=20
analysis. J.-H.S. Hofmeyr, A. Cornish-Bowden. Stellenbosch, Marseille109
An Invariance Property of Co-response Coefficients in Modular Metabolic=20
Control Analysis. J.M. Rohwer, S. Schuster, H.V. Westerhoff. Amsterdam,=20
Berlin109
Error and Bias in Control Coefficient Values as a Consequence of the=20
Non-Linearity of Matrix Method Equations. S. Thomas, D.A. Fell. Oxford110
Bistability and Irreversible Transitions in the PFK/F-1,6-P2ase Cycle in=20
Cell-Free=20
Extracts from Rat Liver. W. Schellenberger, J. Frenzel, K. Eschrich.=
Leipzig111
Irreversible Transitions between Stationary States in the F-6-P/F-1,6-P2=20
cycle in Yeast Extracts. W. Schellenberger, J.-F. Hervagault. Leipzig,=20
Compi=8Agne111
Control over Electron Transfer between Ubiquinol and Cytochrome c During=
Light=20
Driven Electron Transfer. B.J. van Rotterdam et al. Amsterdam,=
Stellenbosch112
Computer Simulation of State 4 State 3 Transitions in Isolated=20
Mitochondria. B. Korzeniewski. Krakow . . . . . . . . . .112
Control Analysis of Stimulation of Oxidative Phosphorylation in Heart=20
Mitochondria by Calcium Ions. V. Mildaziene et al. Kaunas, Moscow, London113
Top-Down Control Analysis of Palmitoyl-CoA Oxidation in Isolated=20
Coupled Rat Liver Mitochondria. R.A. Makins, P.A. Quant. Cambridge114
Object-Oriented Biochemical Simulation Applied to Systems of Dioxygen=20
Free Radical Reactions. J.P.C. Moniz Barreto, J.H. Woods, D.A. Fell.=
Oxford115
Control of the PII Protein in the Glutamine Synthetase Adenylylation=20
Cascade. W.C. van Heeswijk et al. Amsterdam, Castanet-Tolosan116
Protein Burden in Zymomonas mobilis: Negative Flux and Growth Control due to=
=20
Overexpression of Recombinant Protein. J.L. Snoep et al. Gainesville,=20
Amsterdam117
The Determination of Intracellular Fluxes and Intermediate Concentrations=20
In Vivo by Magnetic Resonance Spectroscopy. R. Schuster et al. Berlin,=20
Bordeaux118
Is Light a Substrate? On Microscopic Reversibility of Light Reactions.
G. Mesz=82na, H.V. Westerhoff. Budapest, Amsterdam . . . . .119
Part 3
Coupling and Mechanisms in the Regulation
of Electron, ATP and Ion Fluxes
Leaks and Slips during Mitochondrial Electron Transfer
S. Luvisetto, M. Canton, I. Schmehl, G.F. Azzone. Padova .122
Experimental Discrimination between Proton Leak=20
and Redox Slip during Mitochondrial Electron Transport
M.D. Brand, L.-F. Chien, P.H. Diolez. Cambridge, Bordeaux 125
Permeability of the Inner Mitochondrial Membrane and Respiration
M. Canton, S. Luvisetto, I. Schmehl, G.F. Azzone. Padova .129
The Uncoupling Mechanism of the Anesthetic Bupivacaine
I. Schmehl, M. Canton, S. Luvisetto, G.F. Azzone. Padova .133
Influence of the Mechanism of Change in ATP Synthase-ATPase=20
Stoichiometry on the Control of Oxidative Phosphorylation in situ
X. Leverve, E. Fontaine, P. Espi=82, C. Keriel, B. Gu=82rin, M. Rigoulet.=20
Grenoble, Bordeaux . . . . . . . . . . . . . . . . . . .137
ATP Synthesis in Permeabilized Cells: Assessment of the=20
ATP/O Ratios In Situ
R. Ouhabi, M. Boue-Grabot, J.-P. Mazat. Bordeaux . . . . .141
Permeabilized Spheroplasts as a Tool for Studying the Mecha-=20
nistic Stoichiometry of Yeast Oxidative Phosphorylation
V. Fitton, R. Ouhabi, B. Gu=82rin, M. Rigoulet. Bordeaux . .145
Investigations upon the Effect of Monovalent Cations on=20
Oxidative Phosphorylation in Yeast Mitochondria
S. Manon, X. Roucou, M. Gu=82rin. Bordeaux . . . . . . . . .150
Can Mitochondria Sequester Calcium from Physiological=20
Calcium Pulses?
G. Sparagna, K.K. Gunter, S.-S. Sheu, T.E. Gunter. Rochester154
Mitochondrial Calcium Spiking: The Physiological Face of=20
Permeability Transition?
F. Ichas, L.S. Jouaville, S.S. Sidash, J.-P. Mazat,=20
E.L. Holmuhamedov. Bordeaux, Pushchino, Kalamazoo . . . .159
Developmental regulation of Na+,K+- and Ca2+-ATPases=20
in muscle
M.J. Dauncey, T. Clausen, A.P. Harrison. Cambridge, =8Frhus 163
What is controlling the cell membrane potential?=20
J. Siegenbeek van Heukelom et al. Amsterdam, Moscow . . .169
Effects of Propofol on the Ca2+-Induced Permeability Transition of Rat Heart=
=20
Mitochondria. F. Sztark et al. Bordeaux . . . . . . . . .174
The High Affinity Site of Beef Heart Cytochrome c Oxidase is not=20
Electron Transfer Efficient. F. Nicoletti et al. Rome, Cagliari174
Part 4
The Microenvironment of Mitochondria and Cells:
Diffusion Gradients, Shuttles and Signals
ADP Diffusion Gradients and Metabolic Oscillatory Signals=20
to Mitochondria in Heart and Liver Cells
V.A. Saks, E.V. Vasilyeva, Z.A. Khuchua, Y.O. Belikova, M.K. Aliev,=20
T. Kesvatera, T. Tiivel, K. Anflous, R. Ventura-Clapier, Ch. Keriel,=20
E. Fontaine, X. Leverve. Tallinn, Moscow, Paris, Grenoble 178
Effect of Macromolecules on ADP-Transport into Mitochondria
F.N. Gellerich, F.D. Laterveer, E. Gnaiger, K. Nicolay.=20
Utrecht, Innsbruck . . . . . . . . . . . . . . . . . . . .181
Macromolecules Increase the Channeling of ADP from Mito-=20
chondrially Associated Hexokinase to the Mitochondrial Matrix
F.D. Laterveer, F.N. Gellerich, E. Gnaiger, K. Nicolay.=20
Utrecht, Innsbruck . . . . . . . . . . . . . . . . . . . .186
How does Oxygen Pressure Control Oxygen Flux in Isolated=20
Mitochondria? A Methodological Approach by High-Resolution=20
Respirometry and Digital Data Analysis
G. M=82ndez, E. Gnaiger. Innsbruck, Buenos Aires . . . . . .191
Determination of Creatine Kinase Fluxes with Purified Creatine Kinase=20
and Isolated Mitochondria using 31P Nuclear Magnetic Resonance
S. Soboll, A. Conrad, M. Gruwel. D=81sseldorf . . . . . . .195
Oscillations of Intracellular pH or High Energy Phosphate=20
Content Cannot be Detected by Gated NMR during the Cardiac=20
Cycle of an Isovolumic Perfused Rat Heart
J.A. Hoerter, B. Gillet, P. Mateo, P. Lechene, J.-C. Beloeil.=20
Chatenay Malabry, Gif s/Yvette . . . . . . . . . . . . . .199
The Appearance of the ATP Concentration Gradient in the Intermembrane=20
Space of Mitochondria. T.Yu. Lipskaya, S.P. Bessman. Moscow, Los Angeles201
Energy Flow Around the Outer Mitochondrial Membrane.=20
O. Demin et al. Moscow, Kaunas, Utrecht, Innsbruck, Amsterdam201
How to Vary the Proportion of Dynamic Channelling Flux at Constant Total=
Flux.=20
P. Mendes, D.B. Kell, H.V. Westerhoff. Aberystwyth, Amsterdam202
A New Approach to Knowledge-Based Potentials of Mean-Force in=20
Polypeptides and Proteins. J. Quedenau, H.-G. Holzh=81tter. Berlin203
Part 5
The Impact of Bioenergetics
on Cellular, Physiological and Biotechnological Processes
Chemical Forces in the Cell: Calculations for the ATP System
E. Gnaiger, M. Wyss. Innsbruck . . . . . . . . . . . . . .207
The Flow-Force Relation of Oxidative Phosphorylation=20
in Human Forearm Muscle is Sigmoidal
J.A.L. Jeneson, S.A. Jubrias, M.J. Kushmerick. Utrecht, Seattle213
Muscular Contraction, Dissipation and Schr=94dinger's Negative Entropy
J. Mejsnar, F. Mars=A1k. Praha . . . . . . . . . . . . . . .215
Modelling of Oxidative Phosphorylation in E. coli
P.R. Jensen, J.M. Rohwer, O. Michelsen,=20
H.V. Westerhoff. Lyngby, Amsterdam . . . . . . . . . . . .218
Do Oscillations Control the Bacterial Cell Cycle?
I. Fishov. Beer-Sheva . . . . . . . . . . . . . . . . . .221
A Thermochemical Study of the Production of Lactate by=20
Glutaminolysis and Glycolysis in Mouse Macrophage=20
Hybridoma Cells
R.B. Kemp, S. Hoare, M. Schmalfeldt, C.M.C. Bridge,=20
P.M. Evans, E. Gnaiger. Aberystwyth, Innsbruck . . . . . .226
Catabolic Capacity of Carbon- or Nitrogen-Starved Cultures=20
of Saccharomyces cerevisiae
C. Larsson, A. Nilsson, L Gustafsson. G=94teborg . . . . . .232
Energy Allocation and Material Flux in Fish Hepatocytes=20
under Stress
G. Krumschnabel, W. Wieser. Innsbruck . . . . . . . . . .238
Carbon Flux in Lysine Producing Strain Corynebacterium=20
glutamicum MH20-22B: Analysis by 13C-NMR of Amino Acids=20
and Metabolite Balancing
A. Marx, A.A. de Graaf, W. Wiechert, L. Eggeling, H. Sahm. J=81lich240
Remarks on Biocalorimetry and Biothermodynamics Aimed at=20
Characterization of the Physiological State
B. Zentgraf. Furtwangen . . . . . . . . . . . . . . . . .244
The molecular origin of energy dissipation in mammals. G.C. Brown. London248
Comparison of Thermogenesis in Perfused Skeletal Muscle and=20
Brown Adipose Tissue. A. Matthias et al. Tasmania . . . .249
Mathematical Model of the Human Erythrocyte Describing its Physio-
logical Function. R. Krause, R. Schuster, H.-G. Holzh=81tter. Berlin250
Control of Mitochondrial Oxidative Phosphorylation in Saponin-Skinned Rat=20
M. soleus Fibers. W.S. Kunz, E. Wisniewski, F.N. Gellerich. Magdeburg,=20
Innsbruck250
Downregulation of Protein Synthesis and Turnover in Mitochondria during=20
Cellular Quiescence. S.C. Hand, K. E. Kwast, T.J. Anchordoguy. Boulder251
Life, Death, Dormancy and Social Resuscitation in Non-Sporulating=20
Bacteria. D.B. Kell et al. Aberystwyth, Moscow . . . . .252
Energy Metabolism and Growth Kinetics of Kluyveromyces marxianus=20
in Oxygen-dependent pH-auxostat Culture. Ph. Groeneveld et al. Amsterdam254
Control of Glycolytic Oscillations in Saccharomyces cerevisiae.=20
B. Teusink, K. van Dam, H.V. Westerhoff. Amsterdam . . . .255
Information about Previous Phosphate Fluctuations in the Properties of the=
=20
Phosphate Uptake System of a Blue-Green Alga. G. Falkner, F. Wagner.=
Salzburg256
Part 6
The Impact of Bioenergetics
on Clinical and Pathological Problems
The Permeability Transition Pore. Pathophysiology of a=20
Cyclosporin A-sensitive Mitochondrial Channel
V. Petronilli, A. Nicolli, P. Costantini, R. Colonna, P. Bernardi. Padova259
Mitochondrial Function in the Atrial Appendage of the=20
Human Heart. Characterization by High-Resolution Respirometry
F.N. Gellerich, R. Steinlechner, M. Wyss, T. Eberl, L.C. M=81ller,=20
D. Skladal, W. Sperl, O. Dapunt, R. Margreiter, E. Gnaiger. Innsbruck263
Preservation of Mitochondrial Functions in Human Skeletal=20
Muscle during Storage in High Energy Preservation Solution (HEPS)
D. Skladal, W. Sperl, R. Schranzhofer, M. Krismer,=20
E. Gnaiger, R. Margreiter, F.N. Gellerich. Innsbruck . . .268
Application of Control Analysis to the Study of Metabolic Diseases=20
in Mitochondria. Metabolic Expression of Mitochondrial DNA Mutations
J.-P. Mazat, T. Letellier, M. Malgat, S. Jouaville, R. Morkuniene.=20
Bordeaux, Kaunas . . . . . . . . . . . . . . . . . . . . .272
Change in Flux Control Coefficient of Cytochrome c=20
Oxidase in Copper Deficient Mottled Brindled Mice
A.V. Kuznetsov, J.F. Clark, K. Winkler, W.S. Kunz. Magdeburg, Oxford275
Insulin-Dependent Diabetes Mellitus in MELAS-Mitochondriopathy:=20
Discussion of Possible Causal Relations
K. Oexle, J. Oberle, C. H=81bner . . . . . . . . . . . . . .278
Simulation of the Flow-Force Relation of Oxidative=20
Phosphorylation in Complex I Deficiency
J.A.L. Jeneson, H.V. Westerhoff. Utrecht, Amsterdam . . .280
Oxygen Dependence of Cellular Respiration in Endothelial Cells:=20
A Sensitive Toxicological Test
R. Steinlechner, T. Eberl, R. Margreiter, E. Gnaiger. Innsbruck283
Endothelial Cell Cultures as a Model for Organ Preservation Studies
T. Eberl, R. Steinlechner, W. Salvenmoser, B.=20
Abendstein, M. Rhomberg, H. Schr=94cksnadel, T. Schmid,=20
E. Gnaiger, R. Margreiter. Innsbruck . . . . . . . . . . .288
The Effect of 2-Chlorodeoxyadenosine on Endogenous Respiration=20
of a Human Lymphoma Cell line (U-937)
A. Knoblechner, R. Steinlechner, M. Schirmer, F.N. Gellerich,=20
R. Margreiter, G. Konwalinka, E. Gnaiger. Innsbruck . . .294
Elasticity Analysis in Ischemia-Damaged Heart Mitochondria and Oxidative=20
Phosphorylation System. V. Borutait=82 et al. Kaunas, London, Cambridge297
Kinetics of Tumor Necrosis Factor may Explain High Levels in Tumor Promotion=
=20
and Chronic Inflammation. H. Daams, D. Molenaar, H.V. Westerhoff.=
Amsterdam297
Control Analysis of Trypanosomal Glycolysis for Strategic Drug Design.=20
B.M. Bakker et al. Amsterdam, Brussels . . . . . . . . . .299
Daunorubicin Transport in DNA-containing Plasma Membrane Vesicles from=20
Multidrug-resistant Cells. M. Guiral, J. Lankelma, Hans V. Westerhoff.=20
Amsterdam300
Part 7
Computer Software for Bioenergetics
and Metabolic Control Analysis
Simultaneous Estimates of Single-Enzyme Kinetic=20
Parameters for Multi-Enzymatic Systems Using Artificial=20
Neural Networks
P. Mendes, D.B. Kell. Aberystwyth . . . . . . . . . . . .302
Design of a Software Framework for Flux Determination=20
by 13C NMR Isotope Labelling Experiments
W. Wiechert. J=81lich . . . . . . . . . . . . . . . . . . .305
Calorimetric Investigations with the AT-DSC Method (Alternating=20
Temperature DSC). J.E.K. Schawe, G.W.H. H=94hne. Ulm . . . .311
BioThermoKinetics and the Internet. J.H. Woods, D.A. Fell. Oxford311
