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C J Coscia

Publications and source records attributed to C J Coscia.

At least 91 records · Page 5Linked to original sources
PubMed1980

Effects of norlaudanosolinecarboxylic acids on enzymes of catecholamine metabolism.

Enzymes involved in catecholamine metabolism were assayed in the presence of a new class of naturally occurring tetrahydroisoquinoline alkaloids, the norlaudanosolinecarboxylic acids (NLCAs). NLCAs inhibited tyrosine hydroxylase noncompetitively with respect to its substrate, tyrosine and the cofactor, 6-methyltetrahydropterin (NLCA Kj = 4 x 10(-4) M; 3',4'-deoxynorlaudanosolinecarboxylic acid (DNLCA) Kj = 1.5 x 10(-4) M). Adrenal dopamine-beta-hydroxylase was also inhibited by NLCAs [3'O-methylnorlaudanosolinecarboxylic acid (MNLCA) Kj = 1.2 x 10(-4) M] and NLCA is a competitive inhibitor of norepinephrine methylation by hepatic catechol-O-methyltransferase (NLCA Kj = 5.6 x 10(-5) M). While a slight reduction of rat adrenal monoamine oxidase by MNLCA was also observed, NLCA did not affect the oxidation of tyrosine by D-amino acid oxidase. Kinetic patterns of tyrosine aminotransferase and aromatic amono acid decarboxylase from rat liver were not altered by addition of 1 to 10 x 10(-5) M NLCA or its 3'-O-methyl ether (MNLCA). In vivo studies of brain tyrosine metabolism in mouse neonates corroborated results on the in vitro effect of DNLCA on tyrosine hydroxylase. The potential of high-pressure liquid chromatography was demonstrated in both enzyme assays and radiometric studies of in vivo metabolism.

Animals↗
PubMed1979

Accumulation of a tetrahydroisoquinoline in phenylketonuria.

3',4'-Deoxynorlaudanosolinecarboxylic acid (DNLCA), a tetrahydroisoquinoline derived from dopamine and phenylpyruvic acid, has been detected by computerized mass fragmentography in urine of phenylketonuric children and in urine and brain of rats with experimentally induced hyperphenylalaninemia. Levels of DNLCA in brain of treated animals were more than tenfold higher than controls, and the excess tetrahydroisoquinoline appeared to accumulate in the cerebellum and cortex. DNLCA is a noncompetitive inhibitor of dopamine beta-hydroxylase (inhibition constant, Ki, = 0.42 mM) and is taken up by the brain.

Adolescent↗
PubMed1977

Subcellular localization of a cytochrome P-450-dependent monogenase in vesicles of the higher plant Catharanthus roseus.

The intracellular location of a cytochrome P-450-dependent monoterpene hydroxylase from the higher plant, Catharanthus roseus, has been investigated. By differential and sucrose density gradient centrifugation, utilizing marker enzymes and electron microscopy, the monooxygenase was demonstrated to be associated with vesicles having a membrane thickness of 40-60 nm. The vesicles could be distinguished from endoplasmic reticulum, Golgi apparatus, mitochondria, and plasma membrane and were found in light membrane fractions containing provacuoles. Most definitive results were obtained when seedlings were ground in the presence of sand and in a medium containing sorbitol. Upon subjection of the 20,000-g pellet preparation to linear sucrose density gradient centrifugation, a threefold enrichment in hydroxylase activity was afforded in a yellow band having vesicles varying in size from 0.1 to 0.8 mum in diam and having a density of 1.09 to 1.10 g/cm3. Since the monooxygenase has been implicated in indole alkaloid biosynthesis in this plant, the data suggest the compartmentalization of at least a part of this pathway.

Alcohols↗
PubMed1976

Characterization of a cytochrome P-450 dependent monoterpene hydroxylase from the higher plant Vinca rosea.

A monooxygenase isolated from 5-day old etiolated Vinca rosea seedlings was shown to catalyze the hydroxylation of the monoterpene alcohols, geraniol and nerol, to their corresponding 10-hydroxy derivatives. Hydroxylase activity was inpendent upon NADPH (neither NADH nor combination of NADH, NADP+ and ATP served as substitutes) and O2. Geraniol hydroxylation was enhanced by dithiothreitol (monothiols were less effective) and inhibited by phospholipases, thiol reagents, metyrapone, and cytochrome c, as well as other inhibitors of cytochrome P-450 systems. Geraniol was hydroxylated at a faster rate than nerol, but the alcohols possessed similar apparent Km values. The membrane-bound hydroxylase was solubilized by treatment with sodium cholate, Renex-30, or Lubrol-WX. Cholate-treated enzyme was resolved by DEAE-cellulose chromatography and reconstitution of the hydroxylase was effected utilizing different fractions containing cytochrome P-450, a NADPH-cytochrome c reductase, and lipid.

Binding Sites↗