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Biomedical subjects

C B Stewart

Publications and source records attributed to C B Stewart.

At least 37 records · Page 2Linked to original sources

Antigenic Crossreactivity between Bacterial and Plant Cytochrome P-450 Monoxygenases.

Although cytochrome P-450 monoxygenases mediate critical reactions in plant microsomes, characterization of their activities has been difficult due to their inherent instability and the lack of a crossreacting P-450 antibody. We have surveyed the effects of protein stabilizing agents on t-cinnamic acid hydroxylase (t-CAH), a prominent microsomal P-450, and on total P-450 monoxygenase content. Trans-cinnamic acid is the most effective protecting agent for t-CAH activity. Leupeptin, a broad spectrum protease inhibitor, stabilizes t-CAH activity and increases the apparent P-450 content more than serine protease inhibitors such as phenylmethylsulfonyl fluoride. The combination of t-cinnamic acid and protease inhibitors increase the level of detectable t-CAH activity 4- to 14-fold over the levels detected by previously published procedures. In order to estimate the molecular weights and diversity of the plant P-450 monoxygenases in wounded pea epicotyls, we have prepared two polyclonal antibodies against the Pseudomonas putida camphor hydroxylase (P-450(cam)). One of the heterologous antibodies cross-reacts with constitutive microsomal polypeptides between 52 and 54 kilodaltons and several pea (Pisum sativum L.) mitochondrial proteins between 47 and 48 kilodaltons. The other polyclonal antibody cross-reacts strongly with two wound-induced polypeptides (65 and 47 kilodaltons) and weakly with one constitutive polypeptide (58 kilodaltons). We conclude that at least two subclasses of plant P-450 monoxygenases share common epitopes with the bacterial P-450 enzyme.

Journal Article↗

A novel rat carboxypeptidase, CPA2: characterization, molecular cloning, and evolutionary implications on substrate specificity in the carboxypeptidase gene family.

A new member of the carboxypeptidase gene family, carboxypeptidase A2 (CPA2), has been identified from the predicted amino acid sequence of a rat pancreatic cDNA clone. In vivo recombination and in situ hybridization techniques employing the CPA2 cDNA resulted in the isolation of two genomic clones spanning the 25-kilobase pair rat CPA2 gene. Evolutionary trees built from the amino acid sequences of the known pancreatic carboxypeptidases show that CPA2 and carboxypeptidase A1 (CPA1) are the products of genes which duplicated before the mammalian radiation, and that bovine CPA is of the A1 type. The substrate specificities of CPA1 and CPA2 isolated from rat pancreas are similar to bovine CPA in that carboxyl-terminal amino acids with aromatic or branched aliphatic side chains are preferred. However, the substrate preference of rat CPA1 is skewed toward smaller amino acids, while that of rat CPA2 is skewed toward bulkier amino acids as compared to bovine CPA. The differences in the substrate specificities of these three carboxypeptidases are compatible with the nature of the amino acid replacements in their binding pockets for the carboxylterminal amino acid of the substrate.

Amino Acid Sequence↗

Thiamine deficiency and glyoxylic acid.

The effect of thiamine deficiency on glyoxylic acid metabolism in mice and rats was investigated to determine whether the vitamin deficiency results in gross effects on glyoxylate levels via an alteration in the activity of alpha-ketoglutarate:glyoxylate carboligase. Thiamine-deprived or pyrithiamine-treated mice did not show a decreased oxidation of [1-14C]glyoxylate to respiratory CO2; there was some decrease in the conversion of [2-14C]glyoxylate into CO2 by pyrithiamine-treated mice, but not by thiamine-deprived animals. Dietary thiamine deprivation caused a decrease in carboligase levels in liver but no effect on levels in three brain regions. Pyrithiamine treatment had no significant effect on liver carboligase activities, but did decrease the levels in cerebrum, cerebellum and brainstem. Thiamine-deprived and pyrithiamine-treated mice showed decreased urinary glycolic acid excretion Glyoxylic acid excretion by thiamine-deprived rats was monitored in order to re-examine a previous report by another laboratory that glyoxyluria occurs under these conditions. Trace amounts of glyoxylate could be detected in the urine of rats fed thiamine-deficient diet for 3-5 weeks, but urinary glyoxylate was not detectable at later stages of thiamine deprivation. These results do not support a significant role for alpha-ketoglutarate:carboligase activity in the primary etiology of thiamine deficiency syndromes.

Aldehyde-Ketone Transferases↗

Rapid fluorometric analysis of unbound salicylate in whole blood.

A method has been developed for the analysis of unbound salicylate by membrane cone ultrafiltration of either whole blood or plasma with quantitation by spectrofluorometry. The method was used to study the distribution of salicylate in whole blood over a wide range of concentrations. It was found that at a concentration of 50 ug/ml in whole blood only 9% of the salicylate is present as free drug in the plasma water, while at a concentration of 500 ug/ml, 23% is free. At concentrations exceeding 500 ug/ml the plasma protein binding sites appear to be fully satrated since the free drug concentration increases linearly with respect to the whole blood concentration. Changes in hematocrit have a relatively minor effect on the ultrafiltrate salicylate concentration. The blood/plasma salicylate concentration ratio was found to vary widely over the blood salicylate range studied, 50-1000 ug/ml.

Humans↗