Separation of electronic and hydrophobic effects for the papain hydrolysis of substituted N-benzoylglycine esters.

The role of hydrophobic and electronic effects on the kinetic constants kcat and Km for the papain hydrolysis of a series of 22 substituted N-benzoylglycine pyridyl esters was investigated. The series studied comprises a wide variety of substituents on the N-benzoyl ring, with about a 300,000-fold range in their hydrophobicities, and 2.1-fold range in their electronic Hammet constants (sigma).

Effects of the respiratory tract on inhaled materials.

Inhalation exposure is often compared to intravenous or oral routes of administration with regard to the biological fate of inhaled materials. Such comparisons, however, overlook the contribution of respiratory tract enzymes to the metabolic fate and toxicity of inhaled materials. The effect of respiratory tract metabolism on the toxicity of inhaled materials is thought to be substantial for many compounds for the following reasons.

Inhibition of nasal and liver cytochrome P-450 mono-oxygenases by dioxolanes.

1. A series of six alkyl-substituted dioxolanes were studied for their inhibitory effects on mono-oxygenase activities in vitro with nasal and hepatic microsomes from rats and rabbits. 2.

In vivo metabolism of nasally instilled benzo[a]pyrene in dogs and monkeys.

Metabolism of inhaled materials deposited in the nasal cavity potentially influences their biological fate and toxicity. Metabolic enzymes, including cytochrome P-450-dependent monooxygenases, are not evenly distributed throughout the nasal cavity. The purpose of this study was to determine whether benzo[a]pyrene (BaP) deposited in the nasal cavity could be metabolized and cleared by the nasal tissue in the ethmoid and maxillary turbinate regions of Beagle dogs and cynomolgus monkeys.

Carboxylesterases in the respiratory tracts of rabbits, rats and Syrian hamsters.

Esters are a widespread class of organic compounds found both in industry and the environment. Because esters are often volatile and, therefore, readily inhaled, the capacity of respiratory tract tissues as well as liver S-9 homogenates from rats, rabbits, and Syrian hamsters to hydrolyze a variety of esters was investigated. A new technique to determine hydrolysis rates by measuring carboxylic acid residues using ion chromatography was proven effective.