Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Results of initial studies on methods for determining various model parameters are reported. By employing excised hairless mouse skin in a diffusion cell system, numerous model parameter values were deduced. The stratum corneum permeability was estimated from steadystate fluxes with preparations of heat-separated epidermal membranes. Determinations of dermis diffusivities and enzyme rate constants in situ involved considering the simultaneous transport and the enzyme processes and factoring the diffusivities and enzyme rate constants from the overall kinetics. Dermal diffusivities were on the order of 10-6 cm2/sec for vidarabine and its 5'-valerate ester. The enzyme rate constants were 1.70 x 10-3 sec-1 for the esterase and 8.68 x 10-3 sec-1 for the deaminase.
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PMID:Physical model evaluation of topical prodrug delivery-simultaneous transport and bioconversion of vidarabine-5'-valerate II: Parameter determinations. 51 81

A semiquantitative assessment of estrase and deaminase distributions in hairless mouse skin was performed in vitro. The enzyme activities were quantified using 3H-vidarabine and tis 5'-valerate as the substrates. Full-thickness skin of the hairless mouse was cut into two halves, and each half was homogenized in pH 7.4 buffer. BQOTH THE SUPERNATE AND THE RESIDUE OF THE HOMOGENATE were assayed for esterase and deaminase activities. Results show that the outer half-thickness of the skin contained more esterase but slightly less deaminase than the other half. The characteristics of the esterase and the deaminase reactions also were studied employing the crude enzyme extract; these reactions were essentially irreversible. The deaminase reaction was in the linear region of Michaelis-Menten kinetics for substrate concentrations up to 4.5 x 10(-5) M.
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PMID:Physical model evaluation of topical prodrug delivery--simultaneous transport and bioconversion of vidarabine-5'-valerate IV: Distribution of esterase and deaminase enzymes in hairless mouse skin. 739 37

The mathematical problem of simultaneous transport and metabolism in the case of nonuniform enzyme distributions in the skin was solved, and the solutions were used for analyzing experimental data. Experimental data were obtained from permeation experiments with 3H-vidarabine and its 5'-valerate using cellophane tape-stripped hairless mouse skin. Results of the analyses revealed that the esterase activity was four to nine times higher in the epidermis than in the dermis, whereas the deaminase activity was about the same in the two strata. These results were in good agreement with independent experiments using tissue homogenates. The enzyme distributions and the previously reported diffusivities were employed in generating concentration profiles for the prodrug and the drug in the skin. These results may be used in predicting the possible therapeutic effect of the prodrug when it is topically applied.
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PMID:Physical model evaluation of topical prodrug delivery--simultaneous transport and bioconversion of vidarabine-5'-valerate V: Mechanistic analysis of influence of nonhomogeneous enzyme distributions in hairless mouse skin. 739 38