1.Aspartate deficiency limits peptidoglycan synthesis and sensitizes cells to antibiotics targeting cell wall synthesis in Bacillus subtilis.
Zhao H;Roistacher DM;Helmann JD Mol Microbiol. 2018 Jul 11. doi: 10.1111/mmi.14078. [Epub ahead of print]
Peptidoglycan synthesis is an important target for antibiotics and relies on intermediates derived from central metabolism. As a result, alterations of metabolism may affect antibiotic sensitivity. An aspB mutant is auxotrophic for aspartate (Asp) and asparagine (Asn) and lyses when grown in Difco sporulation medium (DSM), but not in LB medium. Genetic and physiological studies, supported by amino acid analysis, reveal that cell lysis in DSM results from Asp limitation due to a relatively low Asp and high glutamate (Glu) concentrations, with Glu functioning as a competitive inhibitor of Asp uptake by the major Glu/Asp transporter GltT. Lysis can be specifically suppressed by supplementation with 2,6-diaminopimelate (DAP), which is imported by two different cystine uptake systems. These studies suggest that aspartate limitation depletes the peptidoglycan precursor meso-2,6-diaminopimelate (mDAP), inhibits peptidoglycan synthesis, upregulates the cell envelope stress response mediated by σ;M; and eventually leads to cell lysis. Aspartate limitation sensitizes cells to antibiotics targeting late steps of PG synthesis, but not steps prior to the addition of mDAP into the pentapeptide sidechain.
2.Comparison of the effects on lipid metabolism of dietary methionine and cystine between hepatoma-bearing and normal rats.
Kawasaki M;Miura Y;Funabiki R;Yagasaki K Biosci Biotechnol Biochem. 2010;74(1):158-67. Epub 2010 Jan 7.
The effects of dietary supplementation with methionine and cystine on lipid metabolism, including the serum lipid concentration, were studied in Donryu rats subcutaneously implanted with an ascites hepatoma cell line (AH109A) for comparison with normal rats. A diet supplemented with 1.2% L-methionine or L-cystine to 20% casein was found to suppress the hepatoma-induced increases in serum triglyceride and total cholesterol concentration. The lipoprotein lipase activity in tissues was enhanced by dietary methionine and cystine, with no change in the mRNA level. Dietary methionine and cystine increased bile acid excretion into the feces with enhanced hepatic cholesterol 7alpha-hydroxylase activity. Dietary methionine and cystine affected the lipid metabolism differently in normal rats from hepatoma-bearing rats. These results suggest that dietary methionine and cystine each had a hypolipidemic effect against cancer-induced hyperlipidemia, and that the different actions observed in the hepatoma-bearing and normal rats may have been due to a metabolic abnormality caused by the cancer.
3.Theoretical and experimental sulfur K-edge X-ray absorption spectroscopic study of cysteine, cystine, homocysteine, penicillamine, methionine and methionine sulfoxide.
Risberg ED;Jalilehvand F;Leung BO;Pettersson LG;Sandström M Dalton Trans. 2009 May 14;(18):3542-58. doi: 10.1039/b819257j. Epub 2009 Mar 10.
The experimental sulfur K-edge X-ray absorption near-edge structure (XANES) spectra of the amino acids cysteine, homocysteine, penicillamine, methionine, including the oxidation products methionine sulfoxide and the disulfide cystine, have been analyzed by transition potential DFT calculations. The absolute energies and intensities of the main pre-edge sulfur 1s electron transitions have been computed to determine the character of the receiving unoccupied molecular orbitals (MO), and to investigate the influence of external interactions, especially by introducing water molecules hydrogen-bonded to the ionic species present in different pH ranges. When the thiol group deprotonates for cysteine, homocysteine and penicillamine and also for the cysteine residue in glutathione the energy of the main transition, to an MO with antibonding sigma*(S-H) character, reduces by approximately 1.1 eV and the receiving MO obtains sigma*(S-C) character. The changes in transition energy due to hydrogen-bonding were in most cases found to be relatively small, although the transition intensities could vary significantly due to the changes induced in the molecular charge distribution, thereby affecting the shapes of the spectral features.