Mutual inhibition

The Monod kinetic parametos were evaluated by least squares fitting procedures, for tiie single and multiple substrate systems with/without mutual inhibition, and were indicated in Table 1 [6]. The value of indicates the linear decomposition rate. It is dear that the decomposition rate for prc iionic acid is significantly lower than those for acetic add and butyric acid. 

Tam, S.W., and Cook, L. Sigma opiates and certain antipsychotic drugs mutually inhibit (+)3H-SKF-10,047 and 3H-haloperidol binding in guinea-pig brain membranes. Proc Natl Acad Sci USA 81 5618-5621, 1984. 

In systems where several carotenoids are involved, the absorption of each carotenoid is governed by interactions among them carotenoids compete for absorption (Furr and Clark 1997). For example, (3-carotene supplementation reduced absorption of dietary lutein and lycopene in humans (Micozzi and others 1992). Tyssandier and others (2002) found that the absorption of dietary lycopene was reduced when a portion of spinach or pills of lutein were additionally administered to the volunteers. Similarly, the absorption of dietary lutein was reduced by consumption of tomato puree or lycopene pills (Tyssandier and others 2002). Furusho and others (2000) demonstrated that liver retinol accumulation in Wistar rats was significantly reduced when a fixed amount of (3-carotene was replaced by a mixture of (3- and a-carotene, suggesting that each one of these carotenoids mutually inhibits the utilization of the other. The proportion of (3-and a-carotene in the mixture used in that study (Furusho and others 2000) simulated that of carrots. 

Larsson, O. M., Griffiths, R., Allen, I. C., and Schousboe, A. (1986) Mutual inhibition kinetic analysis of gamma-aminobutyric acid, taurine and beta-alanine high-affinity transport into neurons, and astrocytes evidence for similarity between the taurine and beta-ala-nine carriers in both cell types. J. Neurochem. 47,426 132. 

A simple compartmental pharmacokinetic model was proposed by Seaton et al. (1995) to describe the phannacokinetics of hydroquinone in mice, rats and humans. The model did not include hydroquinone sulfation, which does occur in rats and possibly in mice, although glucuronidation is the major reaction. Phenol and hydroquinone may mutually inhibit their sulfation if both are present simultaneously in the rat (Legathe etal., 1994). 

Tardif et al. (1992, 1993 a, 1997) have developed a physiologically based toxicokinetic model for toluene in rats (and humans—see Section 4.1.1). They determined the conditions under which interaction between toluene and xylene(s) occurred during inhalation exposure, leading to increased blood concentrations of these solvents, and decreased levels of the hippurates in urine. Similar metabolic interactions have been observed for toluene and benzene in rats (Purcell et al., 1990) toluene inhibited benzene metabolism more effectively than the reverse. Tardif et al. (1997) also studied the exposure of rats (and humans) to mixtures of toluene, we/a-xylene and ethylbenzene, using their physiologically based pharmacokinetic model the mutual inhibition constants for their metabolism were used for simulation of the human situation. 

UMP becomes bound to site B which catalyzes the hydrolysis of the phosphomonoester bond. Adenosine and 3 -AMP by binding at site B could interfere with the breakdown of cyclic 2, 3 -UMP. Similarly, binding of bis (p-nitrophenyl) phosphate at site A could interfere with the breakdown of 3 -AMP. Cyclic 2, 3 -UMP and bis(p-nitrophenyl) phosphate compete for site A while adenosine competes with 3 -AMP for site B. Unemoto et al. (7) have examined the mutual inhibition of substrates and substrate analogs for the enzyme from halophilic V. alginolyticus. They also concluded that 3 -ribonucleotides and ribonucleo-side 2, 3 -cyclic phosphates are hydrolyzed at different sites. However, because of the nature of the mutual inhibition between 3 -AMP and bis(p-nitrophenyl) phosphate, they suggested that part of the site for the latter substrate overlaps with the 3 -nucleotidase site. At this time the precise mechanism of action of the enzyme is not settled, but clearly there are two active sites, one a 3 -nucleotidase site and a cyclic phosphate diesterase site. Anraku (18) has described this protein as a double-headed enzyme. 

Ahsan, F., et al. 2001. Mutual inhibition of the insulin absorption-enhancing properties of dode-cylmaltoside and dimethyl-beta-cyclodextrin following nasal administration. Pharm Res 18 608. 

Abstract The addition of diisopropylzinc to prochiral pyrimidine carbaldehydes (Soai reaction) is the only known example of spontaneous asymmetric synthesis in organic chemistry. It serves as a model system for the spontaneous occurrence of chiral asymmetry from achiral initial conditions. This review describes the possible kinetic origin of specific experimental features of this reaction. It is shown that generic kinetic models, including enantioselective autocatalysis and mutual inhibition between the enantiomers,... 

While it is commonly accepted that the required mutual inhibition originates from dimerization as expressed by the minimal model, the exact nature... 

In order to observe the chiral amplification given in Fig. 3, two considerations have to be regarded for the choice of the rate parameters (i) the rate constant ko has to be adequately small. For instance, chiral amplification does not occur if ko > 0.2 M 1 s It is apparent that if the chirally unspecific process A + Z R or S proceeds too fast it generates a high amount of racemic matter that can overwhelm the enantiospecific amplification process. (ii) The mutual inhibition rate constant k2 (R + S->-RS) must be higher than k, (R + RR, or it must occur faster than the homodimerization. Moreover, taking into account the equilibrium constants Ahetero = fe/fa and Ana,via = h/ks, it is vital that Ahetero > Aromo. i.e., the heterochiral dimer has to be thermodynamically more stable than its homochiral coun-... 

For Fig. 4, the rate constant for the mutual inhibition (fo) was chosen as the bifurcation parameter however, all other parameters and the initial reactant concentrations serve as bifurcation parameters as well. Mirror-symmetry breaking in simulation is caused by the intrinsic instability of the autocat-alytic model. When placed into the proper parameter domain, this instability can be revealed by the inevitable machine round-off as well as by slightly... 

In the second option, additive-product interactions are assumed. These can lead to the reproduction of enantioselectivity reversal by considering only one additive. The driving force for the enantioselectivity reversal in this case originates from a competition between kinetic steps that give rise to the product R on one hand and to the product S on the other. Due to mutual inhibition, as expressed by the minimal or alternative kinetic model, i.e., R + S++RS (k2, /t3), a process that gives rise to the formation of R is in some way equivalent to an inhibition of the S formation and vice versa. Due to additive-product... 

We have given kinetic insight into a number of experimental features of the Soai reaction. It was shown that chiral amplification and mirror-symmetry breaking are driven by a reaction network that contains enantioselective autocatalysis and mutual inhibition as the essential ingredients. In this sense, the Soai reaction moves the early concepts of Frank forward into experimental reality. Taking into account the formation of isopropylzinc alkoxide dimers, an evaluation of the parameter space in which amplification and symmetrybreaking are observed indicates that the heterochiral dimers display a higher thermodynamic stability and have to be formed faster than the homochiral ones. The necessity of such sensitive interplay may explain why such reactions systems are so scarce. 

The term with ji has the same form as the contribution of Frank s mutual inhibition [16]. The corresponding time evolution of 4> is readily derived in the form of Eq. 13 with coefficients A and B determined by symmetric quantities qi and a = c- q ... 

PROPANOLOL, TIMOLOL CHLORPROMAZINE, HALOPERIDOL t plasma concentrations and efficacy of both chlorpromazine and propranolol during co-administration Propanolol and chlorpromazine mutually inhibit each other s hepatic metabolism. Haloperidol inhibits CYP2D6-mediated metabolism of propanolol and timolol Watch for toxic effects of chlorpromazine and propranolol 1 doses accordingly... 

CALCIUM CHANNEL BLOCKERS CALCIUM CHANNEL BLOCKERS Co-administration of nifedipine and diltiazem leads to t plasma concentrations of both drugs Uncertain, but presumed mutual inhibition of CYP3A isoform-mediated metabolism Monitor PR, BP and ECG at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

TRIMETHOPRIM DAPSONE t levels of both drugs Mutual inhibition of metabolism Be aware - watch for t incidence of side-effects... 

Drugs that are trapped compete with each other for uptake into the organelles. Mutual inhibition of lysosomal trapping results in higher plasma concentrations. This will have the greatest effect on tissues with a low density of lysosomes such as the heart. This interaction may contribute to the increased cardiotoxicity of drugs such as thioridazine when co-prescribed with antidepressants. 

Hydrophilic xenobiotics enter the cell at the sinusoidal side of the hepatocyte membrane by means of transport systems using carrier proteins. These carrier proteins exhibit no or only low substrate specificity, so that various endogenous and also exogenous substances can be transported through the cell membrane. Competition between these substances for carrier proteins may lead to the mutual inhibition of the transport mechanism. 

In a 32-year-old man infected with HIV plasma concentrations of ritonavir, saquinavir, and fusidic acid were significantly raised when these drugs were administered in combination, possibly from mutual inhibition of metabolism (23). 

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