CLASSIFICATION OF ELEMENTARY FLUX MODES IN MITOCHONDRIAL ENERGETIC METABOLISM
(« Physiopathologie Mitochondriale », (« Physiopathologie Mitochondriale », INSERM U688 & Université de BORDEAUX 2)INSERM U688 & Université de BORDEAUX 2)
Marie BEURTON-AIMAR Marie BEURTON-AIMAR
Charles LALÈS (Dcrt)Charles LALÈS (Dcrt)
Jean-Pierre MAZAT Jean-Pierre MAZAT [email protected]
Nicolas PARISEY (Dcrt)Nicolas PARISEY (Dcrt) Sabine PÉRÈS (Dcrte)Sabine PÉRÈS (Dcrte)
- Bernard KORZENIEWSKI - Bernard KORZENIEWSKI (Université de Krakow)(Université de Krakow)
- Christine NAZARET- Christine NAZARET(ESTBB et MAB- Bordeaux 1)(ESTBB et MAB- Bordeaux 1)
- Christine REDER - Christine REDER (MAB- Bordeaux 1)(MAB- Bordeaux 1)
- Pascal BALLET & Abdallah ZEMIRLINE - Pascal BALLET & Abdallah ZEMIRLINE (Université de Brest)(Université de Brest)
- Frank MOLINA & Pierre MAZIÈRE- Frank MOLINA & Pierre MAZIÈRE (CNRS Montpellier)(CNRS Montpellier)
MITOSCOPEMITOSCOPE
MITOCHONDRIA
J.-P. Mazat Jena March 2005
SYMBIOTIC ORIGIN OF MITOCHONDRIASYMBIOTIC ORIGIN OF MITOCHONDRIA
Mitochondria are ancient bacteria. They host
their own genome, their own ribosomes and
a metabolism of procaryotic origin.
AAncncient cellient cell
Bacteria ancestryBacteria ancestryof mitochondriaof mitochondria
DNDNAA
NucleusNucleus
mtDNmtDNAA
mitochondrimitochondriaa
J.-P. Mazat Jena March 2005
Different types of mitochondria
Epithélium Spermatozoo
Butterfly’sAdiposetissue
Rat heart
Mouse Heart
Cortico-surrénales
J.-P. Mazat Jena March 2005
Mitochondrial networkFragmentation
J.-P. Mazat Jena March 2005
Oxidative Phosphorylation and mitochondrial genetics
Complexe I
Succinate
Respiratory chain and ATP synthase Functions of mitochondria
ATP synthesis.
NADH reoxidation
Metabolism
Ca2+ accumulation
Heat production
Free radicals production
Apoptosis
ADN mt ADN nucl.
Complexe I 7 >30
Complexe II 0 4
Complexe III 1 10
Complexe IV 3 10
Complexe V (ATPase) 2 9
Double genetic origin
Sous-unités codées par
J.-P. Mazat Jena March 2005
DECOMPOSITION OF THE MITOCHONDRIAL ENERGETIC
METABOLISM IN ELEMENTARY MODES
J.-P. Mazat Jena March 2005
Succinate
Fumarate
H
H
H
+
+
+
+
H
n
n‘
n
n‘
S
(André CASSAIGNE, Rachid OUHABI & Stéphane LUDINARD)
FAMN FeS
UQb565, b566 FeS ; C1
Cu1 ; Cu2 a ; a3
F0 F1
C I
C II
C III
C IV
DHODH
FAD
Q
G3-PDH
NADH
NAD
Dihydrorotate
Orotate
FADH2
3GP
DHAP
2e2e
2e
2e
2e
Cyt c
2e
O + 2H1/2 2+
H O2
H
H
H
H
H H
n
n
n‘
n‘
S
++
+
+
+
+
ATPATP
ADP ADP 3-3-
4- 4-
Pi Pi
HH+ +
28
2930
31
32
33
34
35
TP
Mitochondrial Metabolism
Citrate
Isocitrate
α-CÉtoglutarate
Succinyl-CoASuccinate
Fumarate
Malate
OxaloacÉtate
Pyruvate
Pyruvate
AcÉtyl-CoA
ADP + Pi
2
NAD
NADH + CO2
H O2
NAD
NADH + CO2
NAD
NADH + CO
GDP + Pi
GTPH O
2
FAD
FADH2
NAD
NADH2
H O2
CitrateMalate
GDP + Pi
GTP
Acyl-CoA (Cn)
Trans enoyl CoA
β-OH-acyl-CoA
β-cÉtoacyl-CoA
Acyl-CoA (n-2C)
AcÉtyl-CoAPropionyl-CoA
MÉthylmalonyl-CoA
En fin d’hÉlice,si nC est impair
ATP + CO2
AMP + PPi
Hs-CoA
Acyl-CoA (>12C) Acyl-CoA (<12C)
Carnitine
Carnitine
Hs-CoA
AcÉtyl-CoA
Carnitine
AcÉtyl-CoA
AcÉtoacÉtyl-CoA
HO mÉthylGlutaryl CoA
AcÉtoacÉtate
HO Butyrate
Hs-CoA
AcÉtyl-CoA
α-CÉtoglutarate Glutamate
NAD NADH
NH3
Carbamyl-P
Citrulline
Citrulline Ornithine
Ornithine
2 ATP + CO2
2 ADP + Pi
Argininosuccinate Arginine UrÉe
Aspartate + ATP
AMP + PPi
Malate
H O2
Pi
18
19
20
21
22
23
Fumarate
SuccinatePi
2-
α-CÉtoglutarateH +
+H
α-CÉtoglutarate
Malate
MalatePi
2-
SuccinateMalate
GlutamateAspartate
Ca
Ca2+
2+
+
Cplx TIM22
CplxOXA1
ATP
8
8
8
1313
13
9
1010
1010
109
9
9
9
9
12
22
54
17
17
2323
44
44
70
70
E
40567
J.-P. Mazat Montpellier Fev 2005
WHY A DECOMPOSITION OF THIS NETWORK
IN ELEMENTARY FLUX MODES ?
-To compare mitochondrial metabolism in different tissues or organisms. How is it possible to obtain different types of mitochondria with the same metabolism ?
J.-P. Mazat Jena March 2005
-To point out specific prevailing pathways, which could be strongly represented in particular tissues and give them their specificity.
- To unveil those mutations, which can be tolerated,those, which cannot and to understand why.
R6i : Pyr + CO2 + ATP = OAA + Pi + ADP .R7i : Pyr + NAD + CoA = ACoA + NADH2 + CO2 .R8i : OAA + ACoA + H2O = Cit + CoA .R9 : Cit = Isocit .R10i : Isocit + NAD = Akg + NADH2 + CO2 .R11i : Akg + NAD + CoA = SucCoA + NADH2 + CO2 . R12 : SucCoA + Pi + ADP = Succ + CoA + ATP .R13 : Succ + FAD = Fum + FADH2 .R14 : Fum + H2O = Mal .R15 : Mal + NAD = OAA + NADH2 . R16 : Akg + NADH2 = Glu + NAD .R17 : Ala + NAD + H2O = Pyr + NH3 + NADH2 .R18 : OAA + Glu = Asp + Akg .R20i : 2 ATP + NH3 + CO2 + H2O = 2 ADP + Pi + CarbamoylP .R21 : CarbamoylP + Ornit = Pi + Citrulline .R25i : 2 ACoA = CoA + AcetoACoA .R26 : ACoA + H2O + AcetoACoA = HmethylGlutCoA + CoA .R27 : HmethylGlutCoA = ACoA + Acetoacetate .R28 : Acetoacetate + NADH2 = Hbutanoate + NAD .R1i : NADH2 + 10 H = NAD + 10 H_ext .R2i : FADH2 + 6 H = FAD + 6 H .R3 : ADP + Pi + 3 H_ext = ATP + 3 H .R4i : H_ext = H .R30 : Acylcarnitine + CoA = Carnitine + AcylCoA .R31i : AcylCoA + 7 FAD + 7 NAD + 7 CoA + 7 H2O = 7 NADH2 + 7 FADH2 + 8 ACoA .T1 : Cit + H + Mal_ext = Mal + Cit_ext + H_ext .T2 : AKG_ext + Mal = Mal_ext + Akg .T3 : AcylC_ext + Carnitine = Carnitine_ext + Acylcarnitine .T4 : ADP_ext + ATP + H_ext = ADP + ATP_ext + H .T5 : Pi_ext + H_ext = Pi + H .T6 : Pyr_ext + H_ext = Pyr + H .T7 : Mal + Pi_ext = Pi + Mal_ext .T8 : Citrulline + Ornit_ext = Citru_ext + Ornit .T9 : Mal + Asp_ext = Mal_ext + Asp .T10 : Hbutanoate = HB_ext .T11 : AA_ext = Acetoacetate .T12 : Asp + Glu_ext + H_ext = Asp_ext + Glu + H .T13 : Mal + Succ_ext = Mal_ext + Succ .T14 : Asp + Succ_ext = Asp_ext + Succ .T15 : Asp + AKG_ext = Asp_ext + Akg .T16 : Asp + Pi_ext = Asp_ext + Pi .T17 : Succ + AKG_ext = Succ_ext + Akg .T18 : Succ + Pi_ext = Succ_ext + Pi .T19 : Akg + Pi_ext = AKG_ext + Pi .T20 : Glu_ext + H_ext = Glu + H .
BIOCHEMICAL REACTIONS INBIOCHEMICAL REACTIONS INENERGETIC ENERGETIC MITOCHONDRIAL MITOCHONDRIAL
MMEETABOLISMTABOLISM
J.-P. Mazat Jena March 2005
45 reactions including 20 transporters
31 metabolites
ENERGETIC MITOCHONDRIAL METABOLIC NETWORK
J.-P. Mazat Jena March 2005
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STOICHIOMETRY MATRIX OF THE ENERGETIC MITOCHONDRIAL METABOLIC
NETWORK
matrix dimension r31 x c45
The following line indicates reversible (0) and irreversible reactions (1)
1 1 1 1 1 1 1 1 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
rows and columns are sorted as declared in the inputfile
N =
J.-P. Mazat Jena March 2005
ELEMENTARY FLUX MODES
435 324 elementary flux modes ! *
How to make things clear ?
Interest ?
* With the help of Stefan KlamtJ.-P. Mazat Jena March 2005
Why such a huge number ?
- many exchangers
- several non-equivalent way to maintain the steady-state of « currency metabolites ».
EXAMPLE OF ELEMENTARY FLUX MODE (1)
T17 – T18 – T19
J.-P. Mazat Jena March 2005
EXEMPLE OF ELEMENTARY FLUX MODE (2)8R8-8R10-8R11-4R20-16R25-5R31-8R9-8R12-(-35)R13-(-35)R14-8R15-(-43)R17-4R21-16-R26-16-R27-16R28-5R30-5T3-(-43)T5-4T8-(-43)T9-16T10-(-43)T12-43T18-43T20
4343
16
16
16
16
16
43
43
43
43
H+
5
5
543
43
8
88
8
88
35
35
43
4343
43
444
J.-P. Mazat Jena March 2005 H
+
TOP 10 OF REACTIONS
R6
T20
R8
T3
R31
R30
T6
R14
R13
T4
Pyruvate carboxylase
Glutamate carrier
Citrate synthase
Acylcarnitine translocase
-oxydation of fatty acids
Acylcarnitine transferase II
Pyruvate carrier
Fumarase
Succinate deshydrogenase
ATP/ADP Translocator
333 737
300 052
290 389
278 232
278 232
278 232
274 024
246 041
246 041
245 698
STEP NAME NUMBER of Elem. Modes
J.-P. Mazat Jena March 2005
CLUSTERING ACCORDING TO « CURRENCY METABOLITE » (1)
FAD/FADH2 : R13 – R2 + 7 R31 = 0
NAD/NADH2 : R7 + R10 + R11 + R15 – R16 + R17 – R28 – R1 + 7 R31 = 0
ADP/ATP : -R6 + R12 – 2 R20 + R3 – T4 = 0
CoA : R7 – R8 + R11 – R12 – R25 – R26 + R30 + 7 R31 = 0
Pi : -R6 + R12 6 R20 – R21 + R3 – T5 – T7 – T16 – T18 – T19 = 0
H+ : 10 R1 + 6 R2 – 3 R3 – R4 + T1 – T5 – T6 – T12 – T20 = 0
J.-P. Mazat Jena March 2005
CLUSTERING ACCORDING TO « CURRENCY METABOLITE » (2)
FAD/FADH2 :
NAD/NADH2 :
ATP/ADP :
CoA :
Pi :
H :
542
7 052
4 165
927
51 281
9 236
Motifs« Currency metabolite »
J.-P. Mazat Jena March 2005
CONCLUSIONCONCLUSION
Analysis of a network in terms of elementary flux modes modes :- Combinatory explosion of the number of elementary modes.- Usefulness ?-Thermodynamic considerations could decrease the number of elementary
modes (metabolite concentrations outside mitochondria will give gradients)
- Kinetic considerations could considerably decrease the number
of elementary modes actually used in a given type of mitochondria.
Metabolism organisation :-are in vivo only some elementary used depending on the cell type ?- or would the metabolism a functioning actually be this mess,
whose the huge number of elementary flux modes give an idea ? J.-P. Mazat Jena March 2005
Important occurrence of some enzymes or exchangers :
pyruvate carboxylase; glu and pyr carriers,…
Implication for mitochondrial diseases
There are less molecule in the cellThere are less molecule in the cell
than elementary modes …..than elementary modes …..
Is it possible that one metabolite participate to all elementary modes in a mito ?
- 500 000 elementary modes = 500 000 true molecules
A mitochondrion is a cube of 1 µm, which gives a volume of 1µm3 = 1 dm3 . (10-5)3 = 10-15 l.
500 000 true molecules = 500 000/6. 10-23 moles 100 000.10-23 = 10-18 moles.
Thus the concentration of this metabolite should have to be :
10-18 moles / 10-15 l = 1 mM
- Kacser, H., Burns, J.A., The control of flux, Symp. Soc. Exp. Biol. 32 (1973) 65-104.
- Heinrich, R., Rapoport, T.A., A linear steady-state treatment of enzymatic chains. General properties, control and effector strength, Eur. J. Biochem. 42 (1974), 89-95.
Kacser, H. and Burns, J.A. 1980. The molecular basis of dominance. Genetics 97: 639-666. A seminal paper answering the long-standing riddle concerning the equivalence of heterozygote with the normal homozygote.
- Reder, C., Metabolic control theory: a structural approach, J. Theor. Biol. 135 (1988) 175-201.
- Groen AK, Wanders RJA, Westerhoff HV, Van der Meer R and Tager JM, Quantification of the contribution of various steps to the control of mitochondrial respiration, J. Biol. Chem. 257 : 2754-2757.
-Tager JM, Wanders RJA, Groen AK, Kunz W, Bohnensack R, Kuster U, Letko , Bohme G, Duszynski J, Wojtczak L : Control of mitochondrial respiration FEBS Lett 151 1-9, 1983.
- David Fell : Understanding the control of metabolism Protland Press 1997, London and Miami.
-Reinhart Heinrich and Stefan Schuster (1996) : The regulation of cellular systems Chapman & Hall.
-Schuster S, Hilgetag C, Woods JH, Fell DA. Reaction routes in biochemical reaction systems: algebraic properties, validated calculation procedure and example from nucleotide metabolism. J Math Biol. 2002;45:153-81
-Papin JA, Stelling J, Price ND, Klamt S, Schuster S, Palsson BO. Comparison of network-based pathway analysis methods. Trends Biotechnol. 2004;22:400-5.
BIBLIOGRAPHIEBIBLIOGRAPHIE
mtDNAtRNA
mRNA
} Subunits of Respiratory Chain
complexesVO2 VATP
MODEL OF mtDNA EXPRESSIONMODEL OF mtDNA EXPRESSION
Respiratory Complex
VO2
WTmtDNA (WTmRNA)
WTmRNA (Complex)
WTmtDNA
VO2
Seuil tARN mt
+ +
100806040200
0
20
40
60
80
100
WTmtDNA (WTmRNA)
WTmRNA (Complex)
MODEL OF mtDNA and of mt-mRNA MODEL OF mtDNA and of mt-mRNA EXPRESSIONEXPRESSION
WTmRNA = 2 * WTmtDNA
KmtDNA + WTmtDNA
(KmtDNA = 100)
Complex = 2 * WTmRNA
KmRNA + WTmRNA
(KmRNA = 100)
THRESHOLD in tRNATHRESHOLD in tRNA
WT-tRNA = 2 * WTmtDNA
KmtDNA + WTmtDNA (KmtDNA = 100)
Complex = 2 * WTmRNA
KmRNA + WTmRNA
(KmRNA = 100)
If tRNA >= tRNA0
Complex = 2 * WTmRNA
KmRNA + WTmRNA
(KmRNA = 100)
If tRNA < tRNA0
2 * WT-tRNA
Km-tRNA + WT-tRNA
(Km-tRNA = 100)
10080604 02000
20
40
60
80
100
Respiratory Complex
Cplxth
VO2th
VO2
Slope = Control Coefficient
MODEL OF COMPLEX EXPRESSION IN FLUXMODEL OF COMPLEX EXPRESSION IN FLUX
1008060402000
20
40
60
80
100
WTmtDNA
VO2
MODEL OF COMPLEX EXPRESSION IN FLUXMODEL OF COMPLEX EXPRESSION IN FLUX
2ème Solution2ème Solution
Traiter la synthèse des protéines et les régulations par des systèmes discrets multivalués :
MetaReg par Ron Shamir & Gat-Viks (Tel-Aviv) :
-Considèrent différents niveaux successifs en remontant de la voiemétabolique (voie de biosynthèse de la lysine chez S. cerevisiae) :
Ac. Am. Ext. / Ac. Am. Perméases / Ac. Am. Int. / Trpt. Comp. N / Trad. Prot. / Cont. Transcription / Enz. / Voie Métabolique
-Les espèces à ces différents niveaux constituent les nœuds du réseau qui sont reliés par des interactions qui sont exprimées selondes tableaux comme ci-dessous :
1
2
3
12
3
00
0
10
1
11
2Etc.
3 - MULTI-AGENTS MODELS (FERBER)
- Agents are entities, objects for which distinctive properties are described :Ex: enzymes, metabolites,…...
- Roles : function representation. Ex : interactions between enzymes andmetabolites, probability of reaction, etc…..
- A group is defined by a set of roles between agents, a graph of interactions and a language or a protocol of interactions.
Collaboration Pascal Ballet et Abdalla Zermiline Université de Brest.
Example : Michaelis - Henri equation:
S + E ES E + P
- E, ES, S and P are agents.
Roles : agent movingcollision and reaction probabilities
System free to evolve.S + E ES E + P
3ème Solution : Réseaux de Petri hybrides3ème Solution : Réseaux de Petri hybridesHFPN (Hybrid Functional Petri Net)HFPN (Hybrid Functional Petri Net)
H. Matsuno et al. : Biopathways Representation and Simulation on Hybrid Functional Petri Net. (http://www.GenomiObjet.Net)
m1
3
Deux sortes de réseaux :
Discontinus : Continus :
m2
m3
21
T
t =1.0If m1 2 and m2 3
P1
P2
P3
m1
m2
m3
T
v = m1 - m2 / 10
P1
P2
P3
Permet une modélisation mixte continu-discontinu avec le même type de représentationPermet la modélisation en même temps (de manière intégrée)des voies métaboliques (glycolyse) et des réseaux génétiques (opéron lactose).
PROJET : MITOCHONDRIE VIRTUELLEMarie Beurton-Aimar, Jean-Pierre Mazat, Christine Nazaret, Nicolas Parisey
et Sabine Pérès
1 - Analyse des modèles existant des ox-phos : .Article et mise sur le web juin 2002 avec aide à l’utilisation des différents modèles. . Application aux courbes de seuil expériemntales (coll. TL)
2 - Modélisation du métabolisme mitochondrial global :Ox-phos, cycle de Krebs, oxydation des acides gras, cycle de l ’urée,….
3 – Construction d’une base de donnée mitochondrieà l’aide du langage d’annotation des processus biologiques Bio. (Collaboration Frank Molina et Pierre Mazières, Montpellier)
4 – Exploration de différentes méthodes de modélisation . Modes élémentaires. . Réseaux hybrides ?
MATRICE DE STOECHIOMÉTRIE - - EXEMPLE 2
X1
V1
V3
V2
N = [ 1 -1 -1 ]V1
V2
V3
= V1 – V2 – V3
dX1
dt
etdX
dt= N . V avec :
dX
dt=
dX1
dtV = =
II
LE CONTRÔLE DES OXYDATIONS PHOSPHORYLANTES
Complexe IComplexe I
CoQCoQ
FAD + 2 FeS centersFAD + 2 FeS centers
Cyt bCyt b FeSFeS Cyt cCyt c 11(Rieske(Rieske))
Complexe IIIComplexe III
Complex IIComplex II
Cyt cCyt c Cyt aCyt a Cyt aCyt a33
Complexe IVComplexe IV( Cytochrome c Oxidase)( Cytochrome c Oxidase)
RotenoneRotenone
AntimycineAntimycineKCNKCN
CHAÎNE RESPIRATOIRECHAÎNE RESPIRATOIRE
NADHNADH
FMN + 5 FeS centersFMN + 5 FeS centers
PyruvatePyruvateGlutamateGlutamate
Succinate, Fatty AcidsSuccinate, Fatty Acids
OO22 HH22OO
NADNAD
J.-P. Mazat Montpellier Fev 2005
KCN µMKCN µM4030201000
Inhibition par le KCN de la Cytochrome-Inhibition par le KCN de la Cytochrome-c-Oxidase et de la vitesse de respirationc-Oxidase et de la vitesse de respiration
0
20
40
60
80
100 A
Letellier et al. (1994) The kinetic basis of threshold effects observed in mitochondrial diseasesLetellier et al. (1994) The kinetic basis of threshold effects observed in mitochondrial diseasesBiochem. J. Biochem. J. 302302 171-174. 171-174.
% C
OX
Act
ivit
y o
r V
O%
CO
X A
ctiv
ity
or
VO
22
% inhibition de la cytochrome c oxidase
0
20
40
60
80
100 B
1008060402000
% R
esp
irat
ory
rat
e (V
O ) 2
J.-P. Mazat Montpellier Fev 2005
COEFFICIENTS DE CONTRÔLE DES OXYDATIVE PHOSPHORYLTION
DANS LES MITOCHONDRIES DE MUSCLE
Pyruvate transport 0.1 0.09
Complex I 0.1 0.15
Complex III 0.26 0.19
Complex IV 0.08 0.10
ATP Synthase 0.11 0.08
Translocase 0.16 0.14
Phosphate Carrier 0.10 0.12
Somme : 0.91 0.87
VATP VO2
COEFFICIENTS DE CONTRÔLE
J.-P. Mazat Montpellier Fev 2005
EFFET DE SEUIL MÉTABOLIQUEdans le cadre de la théorie du contrôle du métabolisme
Le contrôle est partagéLe contrôle est partagé
CCii = 1 = 1
La plupart des coefficients La plupart des coefficients de contrôle sont faiblesde contrôle sont faibles..
Effet de seuilEffet de seuil..
FluxFlux
Étape Étape
InhibiteurInhibiteur
Faible coefficient de contrôleFaible coefficient de contrôle
CCii = = F/F/vvii i
J.-P. Mazat Montpellier Fev 2005
GÉNÉTIQUE MITOCHONDRIALE
hérédité maternelle.
Hétéroplasmie de l’ADN mitochondrial
La proportion (heteroplasmie) de l’ADNmt mutépeut varier de 0 à 100 %
J.-P. Mazat Montpellier Fev 2005
Activité COX
(50 biopsies)
0
2
4
6
0 5 10 15 20 25 30
Vite
sse
de
re
spira
tion
MISE EN ÉVIDENCE D’UN SEUILDANS LES PATHOLOGIES MITOCHONDRIALES
J.-P. Mazat Montpellier Fev 2005
COURBES D’EFFET DE SEUIL MÉTABOLIQUECOURBES D’EFFET DE SEUIL MÉTABOLIQUEComplexe I and IIIComplexe I and III
ROSSIGNOL, R., MALGAT, M., MAZAT, J.-P and .LETELLIER, T., : . (1999) J. Biol. Chem. , 274: 33426-33432.
J.-P. Mazat Montpellier Fev 2005
COURBES D’EFFET DE SEUIL MÉTABOLIQUECOURBES D’EFFET DE SEUIL MÉTABOLIQUEComplexe IV , ATP synt., Pi carrier, Pyr. Carrier, Complexe IV , ATP synt., Pi carrier, Pyr. Carrier,
ANTANT
ROSSIGNOL, R., LETELLIER, T., MALGAT, M., ROCHER, C. AND MAZAT, J.-P. (2000) : Biochem. J. 347 : ROSSIGNOL, R., LETELLIER, T., MALGAT, M., ROCHER, C. AND MAZAT, J.-P. (2000) : Biochem. J. 347 :
45-5345-53..J.-P. Mazat Montpellier Fev 2005
0,50,40,30,20,10,00
10
20
30
40
50
60
70
80
90
100
Complexe IComplexe III
Complexe IV
ATPase
ANT
Transport du Phosphate
Coefficients de Contrôle
Th
resh
old
val
ue
(% in
hib
itio
n o
f is
olat
ed s
tep
act
ivit
y)
y = 90,811 - 153,42x R^2 = 0,805
RELATION ENTRE LES COEFFICIENTS DE CONTRÔLE ET LES VLEURS DE SEUIL
J.-P. Mazat Montpellier Fev 2005