Intrinsic enzyme activity

Ligand-gated ion channels G protein-coupled receptors Receptors with intrinsic enzyme activity INTRODUCTION... 

Plots of initial reaction rates as a function of percentage active subtilisin in the biocatalyst were found to be linear for all biocatalyst preparations. Thus, enzyme activation, as high as 3750-fold in hexane for the transesterification of N-Ac-i-Phe-OEt with n-PrOH, is a manifestation of intrinsic enzyme activation and not of relaxation of diffusional limitations resulting from diluted enzyme preparations. Thus, the above-mentioned hypothesis was refuted. As similar results were found for the metalloprotease thermolysin, activation due to lyophilization in the presence of KC1 may be a general phenomenon. 

Figure 3 Influence of clearance on systemic drug-drug interactions. For model compound A (

For the enzyme employed, the highest conversion occurs at about 50°C. As temperature increases, the intrinsic enzyme activity increases however, enzyme deactivation also becomes significant. Note that, as in the optimum pH, the optimum temperature depends on the source of the enzyme. 

The discovery of compactin and lovastatin prompted efforts to develop derivatives with improved biological properties (163, 164). Modification of the methylbutyryl side chain of lovastatin led to a series of new ester derivatives with varying potency and, in particular, introduction of an additional methyl group a to the carbonyl gave a compound with 2.5 times the intrinsic enzyme activity of lovastatin (165). The new derivative, named simvastatin (124), was the second HMG-CoA reductase inhibitor to be marketed by Merck. Both lovastatin and simvastatin are prodrugs and are hydrolyzed to their active open-chain dihydroxy acid forms in the liver (166). A third compound, pravastatin (125), launched by Sankyo and Squibb in 1989, is the open hy-droxyacid form of compactin that was first identified as a urinary metabolite in dogs. Pravastatin is produced by microbial biotransformation of compactin. 

One fact that can be observed from this limiting-case analysis is that no matter how much intrinsic enzyme activity is present in the liver, the hepatic clearance (CLh) can never be greater than the hepatic blood flow rate ( ()h). ... 

B Receptors with intrinsic enzyme activity C Receptors linked to cytosoiic tyrosine-kinases... 

Currently, there are no known situations in which overproduction of an enzyme or protein can be reasonably attributed to the failure of repression of a gene owing to a defect in its operator. Although there are conditions characterized by excessive enzyme activity, these are related to alterations in enzyme structure such that intrinsic enzyme activity is increased or such that a defect exists in the regulatory controls at the enzyme level. For example, the variant enzyme, glucose-6-phosphate dehydrogenase Hektoen, which has a substitution of histi-... 

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