Tropic acid - CAS 552-63-6

Pseudomonas sp. strain AT3 grew with dl-tropic acid, the aromatic component of the alkaloid atropine, as the sole source of carbon and energy. Tropic acid-grown cells rapidly oxidized the growth substrate, phenylacetaldehyde, and phenylacetic acid. Crude cell extracts, prepared from dl-tropic acid-grown cells, contained two NAD+-linked dehydrogenases which were separated by ion-exchange chromatography and shown to be specific for their respective substrates, dl-tropic acid and phenylacetaldehyde. Phenylacetaldehyde dehydrogenase was relatively unstable. The stable tropic acid dehydrogenase was purified to homogeneity by a combination of ion-exchange, molecular-sieve, and affinity chromatography. It had a pH optimum of 9.5 and was equally active with both enantiomers of tropic acid, and at this pH, phenylacetaldehyde was the only detectable product of tropic acid oxidation. The formation of phenylacetaldehyde from tropic acid requires, in addition to dehydrogenation, a decarboxylation step.

Results of studies carried out in rats for model compounds, D-(-) mandelic acid, benzoylformic acid, and some of their para-alkylated homologs, showed that their biological half-lives determined from the elimination phase of urinary excretion data were longer than those determined from the elimination phase of blood level data. With compounds that followed multicompartment open models, the initial distributive phase (alpha-phase) noted from the blood level data was not detected from the urinary excretion data. Based on the analysis of half-life data obtained in the absence and presence of DL-tropic acid (a competitive renal tubular secretion inhibitor of these compounds), it is proposed that, besides the shortness of the alpha-phase period, the factor accounting for these compounds is their retention and/or detention in the renal tubular membranes during their tubular secretion. Furthermore, it is proposed that the renal tubular membranes do not constitute a part of the central or peripheral compartment.

The effects of DL-tropic acid (VIII) on the distribution pharmacokinetic parameters of the model compounds benzoylformic acid (I), p-methylbenzoylformic acid (II), p-ethylbenzoylformic acid (III), D-(-)-mandelic acid (IV), D-(-)-p-methyl-mandelic acid (V), D-(-)-p-ethylmandelic acid (VI), and D-(-)-p-isopropylmandelic acid (VII) were studied in rats. Since VIII is a competitive inhibitor of renal tubular secretion of I-VII and since all of these compounds (I-VIII) are negligibly bound to plasma proteins and are neither metabolized nor reabsorbed from the renal tubules, they were considered as model compounds. Therefore, changes observed in the values of the distribution pharmacokinetic parameters of I-VII were attributed to the influence of VIII on the transmembrane transport of the compounds between body compartments in rats. The decrease in the apparent volumes of the central compartments for I, IV, and VII, the increase in the apparent volumes of the peripheral compartments for IV-VII, the absence of change in the volumes of the central or peripheral compartments for the other compounds, and the increase in the ratios of the rate constants of the transfer of compounds from one compartment into another for I and IV-VII were explained in terms of the "aqueous pore" mechanism for the transmembrane transport of the anions of the compounds as well as the heteroporosity of the tissue membranes.