Reference

Formation of D-Tyrosyl-tRNATyr Accounts for the Toxicity of D-Tyrosine toward Escherichia coli

Formation of D-Tyrosyl-tRNATyr Accounts for the Toxicity of D-Tyrosine toward Escherichia coli. Soutourina, Olga; Soutourina, Julie; Blanquet, Sylvain; Plateau, Pierre ( Laboratoire de Biochimie, Unite Mixte de Recherche 7654, CNRS-Ecole Polytechnique, Palaiseau 91128, Fr.). Journal of Biological Chemistry, 279(41), 42560-42565 (English) 2004 American Society for Biochemistry and Molecular Biology. CODEN: JBCHA3. ISSN: 0021-9258. DOCUMENT TYPE: Journal CA Section: 10 (Microbial, Algal, and Fungal Biochemistry) D-Tyr-tRNATyr deacylase cleaves the ester bond between a tRNA mol. and a D-amino acid. In Escherichia coli, inactivation of the gene (dtd) encoding this deacylase increases the toxicity of several D-amino acids including D-tyrosine, D-tryptophan, and D-aspartic acid. Here, we demonstrate that, in a Ddtd cell grown in the presence of 2.4 mM D-tyrosine, ~40% of the total tRNATyr pool is converted into D-Tyr-tRNATyr. No D-Tyr-tRNATyr is obsd. in dtd+ cells. In addn., we observe that overprodn. of tRNATyr, tRNATrp, or tRNAAsp protects a Ddtd mutant strain against the toxic effect of D-tyrosine, D-tryptophan, or D-aspartic acid, resp. In the case of D-tyrosine, we show that the protection is accounted for by an increase in the concn. of L-Tyr-tRNATyr proportional to that of overproduced tRNATyr. Altogether, these results indicate that, by accumulating in vivo, high amts. of D-Tyr-tRNATyr cause a starvation for L-Tyr-tRNATyr. The deacylase prevents the starvation by hydrolyzing D-Tyr-tRNATyr. Overprodn. of tRNATyr also relieves the starvation by increasing the amt. of cellular L-Tyr-tRNATyr available for translation.

Absorption and excretion of undegradable peptides: role of lipid solubility and net charge

Absorption and excretion of undegradable peptides: role of lipid solubility and net charge. Pappenheimer, J. R.; Karnovsky, M. L.; Maggio, J. E. (Dep. Biology, Harvard Univ., Bedford, MA, USA). Journal of Pharmacology and Experimental Therapeutics, 280(1), 292-300 (English) 1997 Williams & Wilkins. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 13 Absorption and excretion of undegradable peptides were investigated with use of octapeptides synthesized from D-amino acids.There are some reagents with their cas registry numbers 187345-60-4 and 187345-62-6 are used in this study. D-Tyrosine was included in each peptide to permit labeling with 125I, D-glutamic acid or D-lysine were included to vary net elec. charge and D-serine or D-leucine were included to vary lipid soly. Peptides were administered parenterally or orally to normal rats drinking 5% glucose or maltose. Forty-five percent of a lipid-insol., neg. charged octapeptide added to the drinking fluid in milligram quantities was adsorbed from the intestine and excreted intact in urine; 90% of this peptide as recovered in urine after parenteral injection. In contrast, lipophilic D-octapeptides were largely excreted in feces, even after s.c. injection; the amts. excreted in feces were correlated with oil/aq. partition coeffs. Evidence is presented that lipophilic peptides entering liver cells combine with bile salts to form hydrophilic complexes that are secreted rapidly at high concn. in bile. At physiol. concns. of bile salts (5-40 mM) and nanomolar concns. of peptide, the binding is so complete that these undegradable peptides are rapidly cleared from liver to duodenal fluid in assocn. with the bile salts. After reaching the ileum the bile salts are reabsorbed to blood, leaving the original lipophilic peptides to be excreted in the feces from which they can be extd., purified and identified by high-pressure liq. chromatog. These mechanisms are discussed in relation to (a) the paracellular absorption of peptides and other solutes by solvent drag and (b) the delivery and fate of biol. active peptides. .