Abstract
This paper compares the irreversible and reversible rate equations from several uni-uni kinetic
mechanisms (Michaelis-Menten, Hill and Adair equations) and bi-bi mechanisms (single- and doubledisplacement equations). In reversible reactions, Haldane relationship is considered to be identical for all mechanisms considered and reversible equations can be also obtained from this relationship. Some reversible reactions of the metabolism are also presented, with their equilibrium
constant.
Keywords
Adair Equation, Enzyme Kinetics, Equilibrium Constant, Haldane Relationship, Hill Equation,
Metabolism, Michaelis Menten Equation, Reversible Reactions
1. Introduction
Thermodinamical considerations in a metabolic pathway include different aspects like kinetic analysis, and
identification of reversible steps in this pathway [1]. Although most of the reactions are reversible, it is usual in
general Biochemistry textbooks to present to students kinetic irreversible equations. For instance, the irreversible Michaelis-Menten equation is a well-known example and it is presented in this way in general Biochemistry
books (either to simplify the mechanism, or because this reaction is used for an in vitro study in absence of the
product of the reaction). Nevertheless, when performing an in vivo study, or when using a biochemical mathematical model presenting several reactions of a metabolic pathway, reversible equations should be considered.
In this paper, we present several reversible equations and we compare them with the irreversible ones.
Haldane relationship, an equation which can only be used for reversible reactions, connects biochemical
thermodynamics and biochemical kinetics. Thus, for a reversible uni-uni reaction A = P, Haldane relationship
connects equilibrium constant Keq with kinetic parameters for both irreversible reactions, A P (Vf and KmA)
and P A (Vr and KmP). Haldane relationship is in this case: Keq = Vf KmP/Vr KmA. This is a general relationship
that is also valid for several other mechanisms, including Hill equation (although [P]0.5 and [S]0.5 should replace
the values of KmP and KmA, respectively). Several reversible equations are obtained from the Haldane relationship considering that in equilibrium total velocity should be zero, and that v = vAP vPA. Nevertheless, this
relationship is not considered universal, as when considering a bi-bi reaction with two reactions: A = Q, folHow to cite this paper: Imperial, S. and Centelles, J.J. (2014) Enzyme Kinetic Equations of Irreversible and Reversible Reactions in Metabolism. Journal of Biosciences and Medicines, 2, 24-29. http://dx.doi.org/10.4236/jbm.2014.24005
S. Imperial, J. J. Centelles
lowed by B = P, Haldane relationship will be the product of the two equilibrium constants:
Keq = Keq(1) Keq(2) = (Vf KmQ/Vr KmA ) (Vf KmP/Vr KmB) = Vf2 KmP KmQ/Vr2 KmA KmB.
In general, Haldane relationship for a bi-bi mechanism is an equation more similar to the uni-uni equation:
Keq = Vf KmP KmQ/Vr KmA KmB.
Figure 1. Comparison between the reversible and the irreversible kinetic equations of an uni-uni reaction.
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S. Imperial, J. J. Centelles
Figure 2. Comparison between the reversible and irreversible kinetic equations of a bi-bi reaction.
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S. Imperial, J. J. Centelles
Table 1. Some reversible reactions of the most common pathways in metabolism (extracted from [4]).
Enzyme
(E.C. number)
Reaction
Keq
Alcohol dehydrogenase
(EC 1.1.1.1.)
8.0 1012
Glycerol-3-phosphate
dehydrogenase (EC 1.1.1.8.)
1.0 1012
Lactate dehydrogenase
(EC 1.1.1.27.)
2.76 106
Malate dehydrogenase
(EC 1.1.1.37.)
6.4 1013
Glucose 6-phosphate
dehydrogenase (EC 1.1.1.49.)
6.0 107
Glyceraldehyde-phosphate
dehydrogenase (EC 1.2.1.12.)
0.5
Butyryl-CoA dehydrogenase
(EC 1.3.99.2.)
0.22
Alanine dehydrogenase
(EC 1.4.1.1.)
6.98 1014
Glutamate dehydrogenase
(EC 1.4.1.2.)
4.5 1014
Tetrahydrofolate dehydrogenase
(EC 1.5.1.3.)
1.79 1012
NAD(P) transhydrogenase
(EC 1.6.1.1.)
1.43
9.8 106
Serine
hydroxymethyltransferase
(EC 2.1.2.1.)
10.2
Methylmalonyl-CoA
carboxyltransferase
(EC 2.1.3.1.)
0.526
Ornithine carbamoyltransferase
(EC 2.1.3.3.)
1 105
0.95
1.05
Choline acetyltransferase
(EC 2.3.1.6)
5.1 103
Carnitine acyltransferase
(EC 2.3.1.7.)
1.67
Phosphate acyltransferase
(EC 2.3.1.8.)
1.35 102
Acetyl-CoA acetyltransferase
(EC 2.3.1.9.)
~2 105
Adenine
phosphoribosyltransferase
(EC 2.4.2.7.)
0.1
Aspartate aminotransferase
(EC 2.6.1.1.)
0.16 - 0.17
Alanine aminotransferase
(EC 2.6.1.2.)
2.2
3.86 102
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S. Imperial, J. J. Centelles
Continued
Galactokinase (EC 2.7.1.6.)
26
1.55 104
~8 103
4 102
Phosphoglycerate kinase
(EC 2.7.2.3.)
2.9 104
7.2 109
2.26
320
Dihydropyrimidinase
(EC 3.5.2.2.)
0.67
1.9
Methenyltetrahydrofolate
cyclohydrolase (EC 3.5.4.9.)
2.4 108
Phosphopyruvate carboxylase
(EC 4.1.1.32.)
0.372
Fructosediphosphate aldolase
(EC 4.1.2.13.)
8.1 105
0.325
1.2 104
1.0 - 1.5
2.51 106
0.23
Enoyl-CoA hydratase
(EC 4.2.1.1.7)
16.2
Argininosuccinate lyase
(EC 4.3.2.1.)
1.14 102
Adenylosuccinate lyase
(EC 4.3.2.2.)
6.8 103
Glutamate racemase
(EC 5.1.1.3.)
L-glutamate = D-glutamate
~1
Hydroxyproline epimerase
(EC 5.1.1.8.)
L-hydroxyproline = D-allohydroxyproline
0.99
Ribulosephosphate
3-epimerase (EC 5.1.3.1.)
1.5 - 3.0
UDP-glucose epimerase
(EC 5.1.3.2.)
UDP-glucose = UDP-galactose
0.284
Ribulosephosphate
4-epimerase (EC 5.1.3.4.)
1.86
Methylmalonyl-CoA
racemase (EC 5.1.99.1.)
D-methylmalonyl-CoA = L-methylmalonyl-CoA
1.0
22
Arabinose isomerase
(EC 5.3.1.3.)
D-arabinose = D-ribulose
0.179
L-arabinose isomerase
(EC 5.3.1.4.)
L-arabinose = L-ribulose
~0.11
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S. Imperial, J. J. Centelles
Continued
Xylose isomerase
(EC 5.3.1.5.)
D-xylose = D-xylulose
0.16
Ribosephosphate isomerase
(EC 5.3.1.6.)
0.30
Mannose isomerase
(EC 5.3.1.7.)
D-mannose = D-fructose
2.45
Mannosephosphate isomerase
(EC 5.3.1.8.)
1.78
Glucosephosphate isomerase
(EC 5.3.1.9.)
0.298
Glucuronate isomerase
D-glucuronate = D-fructuronate
0.82
Arabinosephosphate isomerase
(EC 5.3.1.13.)
0.295
L-rhamnose isomerase
(EC 5.3.1.14.)
L-rhamnose = L-rhamnulose
1.5
Phosphoglycerate
phosphomutase
(EC 5.4.2.1.)
2-phospho-D-glycerate = 3-phosphoglycerate
5.0
L-methylmalonyl-CoA mutase
(EC 5.4.99.2.)
L-methylmalonyl-CoA = succinyl-CoA
~20
Muconate cycloisomerase
(EC 5.5.1.1.)
(+)-4-carboxymethyl-4-hydroxyisocrotonolactone = cis-cis-muconate
4.03 102
Valyl-sRNA synthetase
(EC 6.1.1.9.)
0.32
Acetyl-CoA synthetase
(EC 6.2.1.1.)
0.86
Acyl-CoA synthetase
(EC 6.2.1.2.)
~1.5
Succinyl-CoA synthetase
(EC 6.2.1.5.)
0.27
Glutamine synthetase
(EC 6.3.1.2.)
1.2 103
Adenylosuccinatesynthetase
(EC 6.3.4.4.)
2.9 - 10
Propionyl-CoA carboxylase
(EC 6.4.1.3.)
5.7
reactions are usually considered non-controlling reactions in a pathway, but they can be interesting for antagonic
metabolic pathways (i.e. glycolysis and gluconeogenesis), as depending on the intermediate concentrations, they
can be redirected to the products or the substrates.
References
[1]
Alberty, R.A., Cornish-Bowden, A., Goldberg, R.N., Hammes, G.G., Tipton, K. and Westerhoff, H.V. (2011) Reccommendations for Terminology and Databases for Biochemical Thermodynamics. Biophysical Chemistry, 155, 89103. http://dx.doi.org/10.1016/j.bpc.2011.03.007
[2]
Hofmeyr, J.-H.S. and Cornish-Bowden, A. (1997) The Reversible Hill Equation: How to Incorporate Cooperative Enzymes into Metabolic Models. CABIOS, 13, 377-385.
[3]
King, E.L. and Altman, C. (1956) A Schematic Method of Deriving the Rate Laws for Enzyme-Catalyzed Reactions.
The Journal of Physical Chemistry, 60, 1373-1378. http://biokin.com/king-altman/index.html
http://dx.doi.org/10.1021/j150544a010
[4]
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