Metabolic pathways of simvastatin (MK-733), a lactone prodrug of an inhibitor of HMG-CoA reductase, were elucidated in male rats, using the [14C]-labelled compound. Evidence has been obtained for hydrolysis of simvastatin and its metabolites at their 2,2-dimethylbutyryl moieties. Metabolites identified in plasma were 2,2-dimethylbutyric acid (DMB), 2,2-dimethyl-3-hydroxybutyric acid (DMHB) and an open chain hydroxy acid of simvastatin: metabolites identified in urine were DMHB, a glucuronide and the glycine conjugate of DMB. They were characterized by gas chromatography/electron impact and chemical ionization mass spectrometry as phenacyl or pertrimethylsilylated derivatives. The structures of the metabolites and the aglycone of the glucuronide were confirmed as phenacyl esters by comparison of their chromatographic data and mass spectra with those of the phenacyl derivatives of authentic compounds.

Animals↗

PubMedDate not supplied

GmN56, a novel nodule-specific cDNA from soybean root nodules encodes a protein homologous to isopropylmalate synthase and homocitrate synthase.

We have isolated a novel nodule-specific cDNA clone, GmN56, from soybean root nodules. The expression of GmN56 was induced almost concomitantly with the onset of nitrogen fixation, together with leghemoglobin and other late nodulin genes. In situ hybridization studies demonstrated the localization of GmN56 mRNA in the bacterial infected cells of mature nodules. The predicted amino acid sequence of the GmN56 protein exhibits significant homology to those of LeuA (isopropylmalate synthase) of several microorganisms and NifV (putative homocitrate synthase) of nitrogen-fixing bacteria, suggesting that GmN56 encodes an enzyme catalyzing a reaction involving acetyl-CoA and alpha-keto acid as substrates.

2-Isopropylmalate Synthase↗

PubMedDate not supplied

Cariogenic potential of lactosylfructoside as determined by acidogenicity of oral streptococci in vitro and human dental plaque in situ.

The cariogenic potential of lactosylfructoside [O-beta-D-galactopyranosyl-(1-->4)-O-alpha-D-glucopyranosyl-(1<-->2)-beta-D-fructofuranoside] was estimated by experiments on oral streptococci in vitro and human dental plaque in situ. Lactosylfructoside was unable to support growth of the strains of Streptococcus mutans and S. sobrinus used in this study. However, it was able to support growth of strains of S. sanguis, S. mitis and S. oralis. Acid was produced rapidly by cell suspensions of S. oralis ATCC 10557 incubated with lactosylfructoside. Application of 5% w/v solution decreased the pH of human dental plaque. The minimum pH value was below 5.3. The results suggest that lactosylfructoside is as acidogenic as lactose and could be cariogenic if it is consumed frequently and retained for a long period in the mouth.

Acids↗