Research: Science and Education

Appreciating Formal Similarities in the Kinetics W

of Homogeneous, Heterogeneous, and Enzyme Catalysis
Michael T. Ashby
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019; mashby@ou.edu

Catalysts are important to a wide variety of reactions, product, and intermediate are described for the mechanism
from small-scale reactions in the laboratory, and biological of eqs 1 and 2 by the following differential equations (2):
reactions in vivo, through multi-ton catalysis of industrial
d[ A ]
chemicals (1). Not surprisingly, the subject of catalysis is stud- = − k1 [ A ][C ] + k −1 [ AC ] (4)
ied by widely diverse groups of individuals, including chem- dt
ists, engineers, and biologists. To a certain extent, the theory
of catalysis has been developed independently by such groups, d[ AC ]
= k1 [ A ][C ] − k −1 [ AC ] − k 2 [ AC ] {[B]} (5)
particularly with regard to the topics of homogeneous, het- dt
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erogeneous, and enzyme catalysis. Despite the fact that the

theories that span these disciplines share many common de- d[B ]
= − k 2 [ AC][B] (6)
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nominators, the nomenclatures, symbols, abbreviations, forms dt

of the equations, and methods that are employed to analyze
and present data are often dissimilar. Given the emerging in-
terest in interdisciplinary research and the consequential need d[P]
= k 2 [ AC ] {[B]} (7)
to communicate with diverse groups regarding the topic of dt
catalysis, it is desirable to expose students to the subject of
Since [C] << [A]{+ [B]} and [AC] ≤ [C]0, the steady-state
catalysis from diverse perspectives. The purpose of this ar-
(Bodenstein) approximation is applicable (3, 4). Therefore,
ticle is to illustrate the similarities of the kinetic models by
d[AC]兾dt ≈ 0 and we can solve for the steady-state (SS) con-
deriving the rate laws that are commonly employed to de-
centration of the catalyst–substrate adduct (by setting eq 5
scribe homogeneous, heterogeneous, and enzyme catalysis.1
to zero and solving for [AC]SS):
Let us consider homogeneous catalysis first.
k1 [ A ][C ]
Homogeneous Catalysis: [ AC]SS = (8)
The Bodenstein Approximation k −1 + k 2 {[B]}
A catalyst is generally partitioned between a variety of spe-
Homogeneous catalysts (C) generally react with one (A)
cies. For the model of eqs 1 and 2, these species are C (the
or more (B) reactants to form a chemical intermediate (AC)
available catalyst) and AC (the catalyst that is tied up as a
that subsequently reacts to form the final reaction product
substrate adduct). Since mass balance dictates that [C]0 = [C]
(P), in the process regenerating the catalyst (C). The general
+ [AC] (where [C]0 is the initial concentration of catalyst),
equations that will be developed for homogeneous catalysis
we can use eq 8 to determine the quantity of available cata-
here will form the basis later for the presentation of more
lyst:
specialized concepts that are associated with enzyme and het-
erogeneous catalysis. While it is customary to develop the
rate laws for unimolecular (A → P) and bimolecular (A + B α [ A ][C ]0
→ P) reactions separately, I will derive the equations simul- [AC ]SS =
1 + α [A]
taneously. For all of the equations that follow, the unimolec- k1 (9)
ular model can be had by deleting the terms in curly brackets where α =
(e.g., {[B]}) and the equations for the bimolecular model can k −1 + k 2 {[B]}
be had by including these terms. Assuming that the substrate
Note that the mechanism of eqs 1 and 2 (and accordingly
(A) binds to the catalyst (C) reversibly, eqs 1–2 describe a
the aforementioned mass balance equation) assumes the prod-
general mechanism for homogeneous catalysis. Equation 3
uct does not bind to the catalyst. This is not always the case.
is the net reaction.
In fact, the kinetics of product release will be addressed later
k1 in the context of enzyme catalysis.
A + C AC (1) Equations 7–9 can be used to define the rate (velocity =
k−1 v) in terms of a rate law that is based upon the initial con-
k2 centration of catalyst ([C]0, presumably a known quantity):
AC {+ B} P + C (2)
d[P] α k 2 [ A ] {[B]}[C ]0
C v = = (10)
(3) dt 1 + α[ A ]
A {+ B} P
Equation 10 is useful because we can immediately see two
The time dependence of the concentrations of the reactant(s), limiting conditions whereby 1 >> α[A] and 1 << α[A]. Con-

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 Research: Science and Education

sider the former case first. Enzyme Catalysis: Michaelis–Menten Kinetics

Case 1 (1 >> α [ A ] ): Most biological reactions that are kinetically challenged

k1 k 2 [ A ] {[B]}[C ]0
v ≈
α k 2 [ A ] {[B ]}[C ]0 = (11)
k −1 + k 2 {[B]}
Case 1 can be further analyzed in terms of two limiting con-
ditions. For the situation where k᎑1 << k2{[B]}, the first reac-
tion (eq 1) is rate-limiting:
Case 1a (k −1 << k 2 {[B]} ): v ≈
k1 [ A ][C ]0 (12) 6). To fully understand the meaning (and limitations) of the
The other case, where k᎑1 >> k2{[B]}, occurs when the equi-
librium of eq 1 lies on the left,
Case 1b (k −1 >> k 2 {[B]} ):
k
v ≈
1 k 2 [ A ] {[B ]}[C ]0 = K1 k 2 [ A ] {[B]}[C ]0 (13)
k −1
where K1 is the equilibrium constant and equal to k1兾k᎑1. Re-
turning to the limiting conditions for eq 10, the situation
where 1 << α[A] occurs when the catalyst is completely bound
to the substrate and the second reaction (eq 2) is rate-limit-
ing:
Case 2 (1 << α [ A ]): v ≈
k 2 {[B]}[C ]0 (14) (vbreakdown) are given by:
Importantly, case 1 produces a pseudo-first-order rate law
for the unimolecular mechanism, whereas case 2 yields a
pseudo-zeroth-order rate law. The significance of these lim-
iting conditions is illustrated in Figure 1 in which the initial
reaction velocities (v0) are plotted against the initial concen-
tration of substrate ([A]0). The result is “saturation kinetics”
at high concentrations of substrate, which is a hallmark for
the mechanism of eqs 1 and 2.
While it has been useful to explore the limiting condi-
tions for the general steady-state rate law that describes the
mechanism of eqs 1 and 2, it is important to recognize that
it is often not possible to simplify eq 10. The case where the
equilibrium constant K1 is neither large nor small is com-
monplace, and this situation will come into play during the
discussion of enzyme and heterogeneous catalysis.
[ES] =
are catalyzed by specialized proteins that are called enzymes.2
Enzymes are essential to sustain life, and the malfunction of
a single critical enzyme can lead to a severe disease. Enzymes
are also frequently the targets of chemotherapy. Hence, en-
zymology is an important field of study. The most commonly
employed model that is used to study enzyme kinetics was
derived by Leonor Michaelis and Maud Menten in 1913 (5,
model, it is useful to derive the Michaelis–Menten (MM)
equation using the notation and logic that is generally em-
ployed in biochemistry textbooks. We begin with a mecha-
nistic model that involves equilibrium binding of a substrate
(S) with an enzyme (E) (cf. eqs 1 and 2, for the unimolecu-
lar case):
k1 k2
E + S ES E + P
k−1
(15)
In deriving the MM equation, textbooks generally focus on
the ES complex. Thus, the rate (or velocity) of formation of
ES (v formation) and the rate of the “breakdown” of ES
v formation = k1 [E ][ S] (16)
v breakdown = ( k −1 + k 2 )[ ES] (17)
Eqs 16 and 17 are simply a recasting of eq 5. Although the
original derivation of the MM equation assumed that the
equilibrium of eq 15 is rapid (5), it was soon demonstrated
by Briggs and Haldane (BH) that such an assumption is too
restrictive, and in fact, a steady-state approximation (whereby
the formation of ES is approximately equal to the consump-
tion of ES) is the only necessary requirement to complete
the derivation (6). Thus, the steady-state approximation is
generally invoked at this stage of the derivation:
k1 [ E ][ S] = (k −1 + k 2 )[ ES]
⇒
[E ][S]
k −1 + k 2 (18)
k1
Equation 18 is simplified (in appearance) by defining a new
term called the Michaelis constant, KM, which is the recip-
rocal of the term α that was defined in eq 9 (for the uni-
molecular model):

KM =
1 k + k2
= −1 ⇒ [ES ] =
[E ][S]
(19)
α k1 KM
By analogy to eq 9, the [E] and [ES] may be defined in terms
of the total enzyme concentration ([E]T = [E] + [ES]). Thus,
we can multiply the numerator and denominator of eq 10
(with a substitution of analogous variables) by KM:

d[P ] KM α k 2 [E ]T [S] k 2 [E ] T [ S ]
Figure 1. Plot of initial velocities versus the initial concentration of v = = = (20)
dt K M + K M α [S ] KM + [S]
substrate A for the mechanism of eqs 1 and 2 (assuming that the
elective substrate B is in large excess). The MM equation can be had by assuming the maximum

1516 Journal of Chemical Education • Vol. 84 No. 9 September 2007 • www.JCE.DivCHED.org

 Research: Science and Education

Table 1. The Meaning of Vmax and KM for Various Mechanistic Models

Model Vmax KM Eq a
b
Rapid Equilibrium Binding of S (MM) k2[ET] k1/k−1 15

Steady-State Binding of S (BH) k2[ET] (k1 + k2)/k−1 18

Rate-Limiting Release of P (k2k3[ET])/(k2 + k−2+ k3) (k−1k−2 + k−1k3 + k2k3)/k1(k2 + k−2+ k3) 23
a b
The rate constants are defined in these equations. The equilibrium is rapid.

velocity is achieved when the catalyst is saturated by the sub-

strate such that v = Vmax = k2[E]T. Substituting Vmax into eq
20 gives the usual form of the MM equation:

Vmax [S]
v = (21)
KM + [S]
Thus, eq 21 is based upon all of the assumptions that went
into the derivation of eq 10, and the limiting conditions that Figure 2. Schematic of the Langmuir–Hinshelwood mechanism.
are described by eqs 11–14 apply to the MM equation as
well. While eq 21 is the one that is used most often in text-
books to describe enzyme kinetics, it is noteworthy that the
models on which eq 21 is based (i.e., the rapid equilibrium has occurred, the products are released. Different kinetic
model of MM and the steady-state model of BH) are gener- models for reactions on surfaces have been proposed. We will
ally unrealistic, because the irreversible step of eq 15 includes focus here on the Langmuir–Hinshelwood (LH) model,
the catalytic reaction step itself, as well as all the protein con- which is named after Irving Langmuir (1932 Nobel Prize in
formation changes that occur before and after that step. In Chemistry) and Cyril Norman Hinshelwood (1956 Nobel
fact, the chemical reaction is seldom the turn-over-limiting Prize in Chemistry).3 Derivation of the rate law for the LH
step of an enzyme-catalyzed reaction, but rather conforma- mechanism generally begins with the symbolism that was em-
tional changes in the protein that are associated with the re- ployed by Langmuir in his original work on the reversible
lease of the product are frequently rate-limiting (7). Thus, it adsorption of molecules from the gas phase to solid surfaces
is appropriate to include that step in the mechanism as well: (8, 9). This model was subsequently exploited by
Hinshelwood for reactions that are catalyzed by the surface
k1 k2 k3 (S, Figure 2).
E + S ES EP E + P (22) Derivation of the LH rate law begins with the assump-
k−1 k−2 tion that the reaction of the substrate(s) (A´ and {B´}) on
A rate law for the mechanism of eq 22 is readily derived (see the surface (S) is rate-limiting. Thus the rate, r, is defined as
the Supplemental MaterialW): r = k 3 [A′ ] {[B′ ]} (24)
It is furthermore assumed that the binding of the substrates
k2 k 3 [E] T in the gas-phase (A and {B}) to the surface is under equilib-
[ S] Vmax [S] rium control, where S* are the vacant surface sites:
k 2 + k −2 + k 3
v = =
k −1 k −2 + k −1 k 3 + k 2 k 3
+ [S ] KM + [S] (23)
k1 ( k 2 + k −2 + k 3 ) K1 =
[ A ′ ] and K 2 =
[B′ ]
(25)
S* [ A ] S* [B ]
It is important to recognize that while the original MM (rapid
equilibrium) mechanism, the BH (steady-state equilibrium) In writing eq 25, we are making an inherent assumption that
mechanism, and the mechanism of eq 22 (rate-limiting re- there are a fixed number of localized surface sites present on
lease of product) give rise to equations for which the mean- the surface. This is the first major assumption of the so-called
ings of Vmax and KM are different (Table 1), all three equations Langmuir isotherm. It is also possible to redefine the equi-
yield analogous hyperbolic functions (eq 21). Thus, the ob- libria of eq 25 in terms of the total surface coverage (θ) and
servation of “Michaelis–Menten”-like kinetics does not un- the partial pressures of the gases (P ). The maximum (satura-
ambiguously define the operative mechanism.1 tion) surface coverage of an adsorbate on a surface is taken
to be unity, that is, θmax = 1. Since [A´] = θA, S* = 1 − θA,
and [A] ∝ PA, we can define new adsorption equilibrium con-
Heterogeneous Catalysis: stants (which are sometimes given the symbol β):
The Langmuir–Hinshelwood Model
θA
Heterogeneous catalysis involves a surface on which the βA =
reactants (which are in a different phase, either gaseous or (1 − θA {− θ B } ) PA
liquid) temporarily become adsorbed (8, 9). Once bound to
θB (26)
the surface, bonds in the substrate become sufficiently weak- and βB =
ened that chemical reactions are possible. After the reaction (1 − θA − θ B )PB

www.JCE.DivCHED.org • Vol. 84 No. 9 September 2007 • Journal of Chemical Education 1517

 Research: Science and Education

As with all chemical reactions, the equilibrium constant (β)
is both temperature-dependent and related to the Gibbs free
energy (and hence to the enthalpy change for the binding
process). It is noteworthy that β is only independent of θ if
the enthalpy of adsorption is independent of coverage. This
is the second major assumption of the Langmuir isotherm.
Rearrangement of eq 26 gives an expression of surface cover-
age:
Catalysis In Vivo: Monod’s Law
As an aside, it is noteworthy that hyperbolic functions
such as those that describe the aforementioned catalytic reac-
tions are pervasive in nature. For example, the following equa-
tion has been used by Jacques L. Monod (1965 Nobel Prize
in Medicine) to describe the relationship between bacterial
growth and the concentrations of essential nutrients (10):

βA PA Growth ≡ R = R C
θA = rate K
1 + βA PA {+ βB PB} C1 + C

βB PB (27) [glucose] (30)

and θ B = = 1.35 (division/h) −5
1 + βA PA + βB PB (2.2 × 10 M) + [glucose]

For the unimolecular reaction:
k 3 βA PA
r = k 3 [ A ′
] = k 3 θA = (28) trient, RK is the rate limit for increasing concentrations of C,
1 + βA PA
One can immediately see the similarities between eq 28 and
the corresponding equation for homogeneous catalysis (eq
10). Thus, two limiting conditions exist: 1 >> βAPA (e.g., at
low pressures of A) and 1 << βAPA (e.g., at high pressures of
A). For the former, as a consequence of low surface cover-
age, the reaction is pseudo-first-order and linearly dependent
on the pressure of A. For the latter situation, as a consequence
of high surface coverage, the reaction is pseudo-zeroth-order
and independent of the pressure of A (cf. Figure 1). An analo-
gous set of equations can be derived for the bimolecular re-
action:
k 3 βA PA βB PB
r = k 3 [ A ′
][B′
] = k 3 θA θB = (29)
(1 + βA PA + βB PB)
2 Monod’s law for microbial metabolism (eq 30) exhibit differ-
However, eq 29 does not give rise to the simple behavior of
Figure 1. The LH model is based upon the assumption that
A and B compete for the same vacant sites on the surface. As
the PA increases, eventually the surface becomes saturated with
A, leaving no sites for binding B, and consequently lower
reaction rates are observed. For the situation where the PB is
held constant, Figure 3 illustrates the effect of increasing the
PA for a LH model of bimolecular catalysis.
Equation 30 summarizes data that Monod reported for the
bacterium Escherichia coli as a function of glucose concen-
tration (10), where C stands for the concentration of the nu-
and C1 is the concentration of nutrient at which the rate is
half its maximum value. By analogy to the MM equation (eq
20), RK = V max = maximum rate of growth (in units of
divisions兾h) of E. coli. and C1 has a meaning that is analo-
gous to KM. Saturation kinetics are observed when the me-
tabolism of glucose (a catalytic process) in no longer
concentration-limited.
Summary
While the final forms of the rate laws for the Bodenstein
approximation for homogeneous catalysis (eq 10), the Michae-
lis–Menten model for enzyme catalysts (eq 21), the Langmuir–
Hinshelwood model for heterogeneous catalysis (eq 28), and
ent appearances, they are all based upon similar premises and
are consequently subject to corresponding limitations. When
the approximations that go into the derivations of these rate
laws are valid, they all exhibit the same limiting relationships
(for unimolecular reactions), namely pseudo-first-order kinetic
and substrate concentration dependencies when the catalysts
are unsaturated, and pseudo-zeroth-order kinetics and sub-
strate concentration independencies when the catalysts are
saturated. The steady-state approximation can in principle be
invoked for all of these models. Given the widespread use of
these models, it is worthwhile to consider the implication (and
limitations) of that approximation. The steady-state model for
the unimolecular reaction of eqs 1 and 2 is derived by setting
eq 5 to zero. However, that approximation is unnecessarily
strict. By substituting [C] = [C]0 − [AC] into eq 5, solving
for [AC], and inserting that result into eq 4 (with the same
substitution of [C] = [C]0 − [AC]), the following relationship
can be derived (11):

(k 1 [ A ] + k −1 ) [dt ]
d AC
d[A]
−d k1 k 2 [ A ][C ]0
= + (31)
dt k1 [ A ] + k −1 + k 2 k 1 [ A ] + k −1 + k 2

Figure 3. Anticipated effect of PA on the reaction rate, r, for a bi- Equation 31 differs from eq 11 in that it contains k1[A] in
molecular Langmuir–Hinshelwood mechanism when PB is held con- the denominator of the first term and it bears a second term.
stant. To arrive at eq 11, k1[A] must be much less than k᎑1 + k2 and

1518 Journal of Chemical Education • Vol. 84 No. 9 September 2007 • www.JCE.DivCHED.org


the second term must be insignificant with respect to the first
term. The first requirement clearly implies the rate of for-
mation of AC is less than its rate of destruction. Regarding
the second requirement, the following must be true:
d [ AC ] k 1 k 2 [ A ] [C ]0
<< (32)
dt k 1 [ A ] + k −1
Equation 32 is significantly less severe than the assumption that
d[AC]兾dt = 0, and it is the only requirement for application of
the steady-state approximation to the mechanism of eqs 1 and
2 when the second reaction step (eq 2) is rate-limiting.
Acknowledgments
This work was supported by the National Science Foun-
dation (CHE-0503984), the American Heart Association
(0555677Z), and the Petroleum Research Fund (42850-AC4).
The author appreciates helpful discussions with Paul F. Cook
and the assistance of Peter Nagy and Kelemu Woldegiorgis,
who proofed the equations. The helpful suggestions of review-
ers are also acknowledged. This contribution is dedicated to
Jack Halpern on the occasion of his 80th birthday.
W
Supplemental Material
It is not necessary to make any assumptions when de-
riving a rate law provided that a closed solution exists for the
differential equations that describe the mechanism. Rate laws
are often readily obtained with the assistance of symbolic
mathematics programs. However, in many cases the differ-
ential equations can be very complicated unless some assump-
tions are made concerning the boundary conditions. This is
certainly the case for the differential eqs 4–7. For cases where
a closed solution does not exist, numerical integration (Euler’s
method) can be used to make a comparison between models
that are derived using approximations (such as the steady-
state approximation) and exact models. A representative
Mathematica input file that depicts the numerical solution
to differential eqs 4–7 (with a comparison with the approxi-
mation of eq 11) and a derivation of eq 23 are available in
this issue of JCE Online.
www.JCE.DivCHED.org • Vol. 84 No. 9 September 2007
Research: Science and Education
Notes
1. It is important to point out from the outset that kinetic
models such as those that are described herein are frequently over-
simplifications. Furthermore, adherence of kinetic data to a par-
ticular model does not prove a mechanism. In fact, it is frequently
the case that a given rate law can be consistent with alternative
mechanisms. An adage that is often repeated is that mechanisms
cannot be proven, but in some cases alternative mechanisms can
be disproven (12). Differentiation between alternative mechanisms
is sometimes possible by kinetic methods alone, but it is often nec-
essary to employ “extra-kinetic” approaches to investigate mecha-
nisms (e.g., the isolation of a kinetically competent intermediate).
2. Some ribonucleic acids (RNAs) also exhibit catalytic ac-
tivity, but to differentiate them from protein enzymes, they are re-
ferred to as ribozymes.
3. In addition to the Langmuir–Hinshelwood mechanism
(which involves initial adsorption of A and B to the surface of the
catalyst), there is also the Rideal–Eley mechanism (which involves
reaction of an incoming B molecule with a molecule of A that is
bound to the catalyst).
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4. Bodenstein, M. Z. Physik. Chem. 1913, 85, 329–400.
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• Journal of Chemical Education 1519