Michaelis constant meaning

A large Michaelis constant means that a- high substrate concentration is necessary to attain half saturation the enzyme possesses a low affinity for the substrate in question. It will preferentially bind another substrate whose Michaelis constant is smaller and probably bring that substrate to reaction, too. Michaelis constants usually range between 10 and 10 moles/liter. 

Km for an enzymatic reaction are of significant interest in the study of cellular chemistry. From equation 13.19 we see that Vmax provides a means for determining the rate constant 2- For enzymes that follow the mechanism shown in reaction 13.15, 2 is equivalent to the enzyme s turnover number, kcat- The turnover number is the maximum number of substrate molecules converted to product by a single active site on the enzyme, per unit time. Thus, the turnover number provides a direct indication of the catalytic efficiency of an enzyme s active site. The Michaelis constant, Km, is significant because it provides an estimate of the substrate s intracellular concentration. 

Stated another way, the smaller the tendency of the enzyme and its substrate to dissociate, the greater the affinity of the enzyme for its substrate. While the Michaelis constant often approximates the dissociation constant fCj, this is by no means always the case. For a typical enzyme-catalyzed reaction,... 

If a reaction that must be investigated follows a reaction sequence as in Scheme 10.1, and if the reaction order for the substrate equals unity, it means that (with reference to Eq. (4 b)), the observed rate constant (k0bs) is a complex term. Without further information, a conclusion about the single constants k2 and fCM is not possible. Conversely, from the limiting case of a zero-order reaction, the Michaelis constant cannot be determined for the substrate. For particular questions such as the reliable comparison of activity of various catalytic systems, however, both parameters are necessary. If they are not known, the comparison of catalyst activities for given experimental conditions can produce totally false results. This problem is described in more detail for an example of asymmetric hydrogenation (see below). 

Button, D. K. (1991). Biochemical basis for whole-cell uptake kinetics specific affinity, oligotrophic capacity, and the meaning of the Michaelis constant, Appl. 

Although Ymax/ m is traditionally treated as a first-order rate constant for enzyme reactions at low substrate concentration, Northrop recently pointed out that V JK actually provides a measure of the rate of capture of substrate by free enzyme into a productive complex or the complexes destined to go on to form products and complete a turnover at some later time. His analysis serves to underscore the concepts (a) that any catalytic cycle must be characterized by the efficiency of reactant capture and product release, and (b) the Michaelis constant takes on meaning beyond that typically associated with affinity for substrate. Consider the case of an enzyme and substrate operating by the following sequence of reactions ... 

By means of an apparent Michaelis constant (A mapp) together with a maximum rate ( max) of butadiene metabolism both obtained with human liver microsomes (Filser et al., 1992), Filser et al. (1993) constructed a human model which was later extended by Csanady et al. (1996) for the butadiene metabolites epoxybutene and diepoxybutane. For butadiene and epoxybutane, the required human tissue air partition coefficients were measured using autopsy material (Table 23). Filser et al. (1993) investigated the influence of styrene co-exposure on butadiene metabolism by assuming competitive interaction. Simulations for a 70-kg man exposed over 8 h to 5 or 15 ppm [11 or 33 mg/m3] butadiene indicated total amounts of butadiene metabolized of 0.095 and 0.285 mmol, respectively, reduced by about 19% and 37% as a result of co-exposure to 20 and 50 ppm styrene, respectively. No influence of butadiene on styrene metabolism was noted. 

FIGURE 6-11 Effect of substrate concentration on the initial velocity of an enzyme-catalyzed reaction. V max is extrapolated from the plot, because V0 approaches but never quite reaches /max. The substrate concentration at which V0 is half maximal is Km, the Michaelis constant. The concentration of enzyme in an experiment such as this is generally so low that [S] >> [E] even when [S] is described as low or relatively low. The units shown are typical for enzyme-catalyzed reactions and are given only to help illustrate the meaning of V0 and [S]. (Note that the curve describes part of a rectangular hyperbola, with one asymptote at /max. If the curve were continued below [S] = 0, it would approach a vertical asymptote at [S] = — Km.)... 

The Michaelis constant, KM, for an enzyme-substrate interaction has two meanings (1) Ku is the substrate concentration that leads to an initial reaction velocity of V" /2 or, in other words, the substrate concentration that results in the filling of one-half of the enzyme active sites, and (2) KM = (k2 + ki)/kv The second definition of Ku has special significance in certain... 

Significance of the Michaelis Constant, Km. The Michae-lis constant Km has the dimensions of a concentration (molarity), because k x and k2, the two rate constants in the numerator of equation (23), are first-order rate constants with units expressed per second (s 1), whereas the denominator fc is a second-order rate constant with units of m-is-1. To appreciate the meaning of Km, suppose that [S] = Km. The denominator in equation (25) then is equal to 2[S], which makes the velocity v = VmaJ2. Thus, the Km is the substrate concentration at which the velocity is half maximal (fig. 7.6). 

Glutamate dehydrogenase has a relatively high Km for ammonia. The high Michaelis constant, Km, means that this system operates most... 

Magnetic moment, 153, 155, 160 Magnetic quantum number, 153 Magnetization, 160 Magnetogyric ratio, 153, 160 Main reaction, 237 Marcus equation, 227, 238, 314 Marcus plot, slope of, 227, 354 Marcus theory, applicability of, 358 reactivity-selectivity principle and, 375 Mass, reduced, 189, 294 Mass action law, 11, 60, 125, 428 Mass balance relationships, 19, 21, 34, 60, 64, 67, 89, 103, 140, 147 Maximum velocity, enzyme-catalyzed, 103 Mean, harmonic, 370 Mechanism classification of. 8 definition of, 3 study of, 6, 115 Medium effects, 385, 418, 420 physical theories of, 405 Meisenheimer eomplex, 129 Menschutkin reaction, 404, 407, 422 Mesomerism, 323 Method of residuals, 73 Michaelis constant, 103 Michaelis—Menten equation, 103 Microscopic reversibility, 125... 

Penicillin G amidase was immobilized on pre-fabricated carriers or insolubUized as crosslinked crystals. Eupergit-related value for R (mean particle radius of swelled carrier) was 80 pm [87]. V , (assuming maximum intrinsic activity per accessible catalyst volume, based on active enzyme molecules 1 unit=l pmol min at 28°C) was 90 and 170 U cm for Eupergit C and 250L, respectively [87]. D ff (effective diffusion coefficient) was taken from literature [87] or calculated as shown in the text. Km (intrinsic Michaelis constant) was uniformly taken as 13 mM [87] and S = 268 mM corresponds to the substrate concentration at catalyst surface of a 10 % solution of penicillin G salt, q was calculated according to Atkinson et al. for spherical particles [85]. For simplification, surface and pore related indices have been omitted. 

MichaeUs Constants. Roche (R19) and Sarles (S6) suggested that the measurement of the afiBnity constant of the substrate for alkaline phosphatase might be a valid means of characterizing the organ sources in hyperphosphatasemia. Later, Moss and King (M36) were able to characterize isoenzymes in different tissues by the determination of Michaelis constants with j3-naphthyl phosphate as substrate. The tissue difference in values, although small, was found to be reproducible. 

The Km values of enzymes range widely (Table 8.4). For most enzymes, lies between 1 and 1 M. The Km value for an enzyme depends on the particular substrate and on environmental conditions such as pH, tempera, ture, and ionic strength. The Michaelis constant, Km, has two meanings. First,... 

All model parameters were well estimated by the validation data set, except the Michaelis constant (Km), which had a relative difference of more than 200%. As might be guessed, one problem with this approach is the difficulty in interpreting the results When do two parameters differ sufficiently in their values so as to render the model invalid Also, if only one parameter is appreciably different, as in this case, does this mean the whole model is not valid Because the Michaelis constant was off by 200%, does this mean the whole model was not applicable to the validation data set In this instance, the authors concluded the pharmacokinetics of dutasteride were similar between the validation data set and index data set and then went on to explain away the difference in Michaelis constants between the data sets. 

The use of K to represent the Michaelis constant (as distinct from the dissociation and kinetic constants) as determined from the kinetic data by graphical analysis, where the biological meaning is unknown and of K, representing the true dissociation constant of the ES complex or substrate constant has been described in an earlier work (Dixon and Webb, 1958). 

Km the first-order rate constant for metabolism of dmg or [in context] the Michaelis constant in non-linear pharmacokinetics Ko the zero-order elimination rate constant Mother the first-order rate constant for elimination of dmg by a process other than metabolism or renal excretion Kio for a two-compartment dmg, the first-order rate constant for elimination of dmg from the central compartment Ki2 for a two-compartment drug, the first-order rate constant for transfer from the central to the peripheral compartment K21 for a two-compartment drug, the first-order rate constant for transfer from the peripheral to the central compartment MAT mean absorption time mean residence time in the gastrointestinal tract synonymous with MRTgit... 

It is important to note that the derivation of the rate law in the Briggs-Haldane mechanism gives the same result as in the Michaelis-Menten mechanism, namely the fundamental Michaehs-Menten equation (3.9). However, in the former case, the Michaelis constant Ka is increased by a factor k /k, compared with the latter case Vmax constant has the same meaning in both mechanisms. 

The meaning of the Michaelis constant (K ) is more complex. There are two extremes. When /c, >> then /fci, which is the dissociation constant (Kj) for the enzyme-... 

Derivation of the Michaelis-Menten equation using the suits of the Mathcad symbolic redactor is given in Fig. 2.24. Here, Km is the Michaelis constant whose physical meaning corresponds to the dissociation constant for the enzyme-substrate complex. Km = k jk. ... 

Km is known as the Michaelis constant and has. in neral. no physical meaning. Its numerical value is that of the substrate concentration at half-maximal velocity it is expressed in units of molarity (M). Figure 8 illustrates the graphical determination of Km for a reaction measured in the presence of enzyme. At that concentration, half the enzyme molecules are bound to the substrate (cf. central part of Fig. 9). 

In one particular case, nevertheless, the Michaelis constant Km takes on a real physical meaning. When the rate of decomposition (t>2 and kz) of the enzyme-substrate complex into P and E is negligible compared to the rates of formation (t>i and ki) and of dissociation (o-i and k i) of this complex, then equations (24) to (28) can be simplified by eliminating the trams comprising the constant kz. The Michaelis constant Km is equal, in this case, to k Jkt, i-e. to the dissociation constant of the enzyme-substrate complex. 

This expression gives another meaning to the Michaelis constant. When = [S] then V = V J2. Using these parameters, it is also useful to define the catalytic constant of an enzyme as... 

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