Biosynthesis of propyl cannabinoid acid and its biosynthetic relationship with pentyl and methyl cannabinoid acids

Biosynthesis of propyl cannabinoid acid has been determined by in vitro incubation with a crude enzyme solution from three strains of Cannabis sativa using ¹⁴C-labelled cannabinoid acid. Biosynthetic relationships between methyl, propyl and pentyl cannabinoid acids have been demonstrated.     

A pronounced sex difference when two linked loci of the Japanese brown frogRana japonica are recombined

To investigate the sex differences of crossing-over inRana japonica, the recombination frequencies between two linked loci,LDH-B andMPI, were examined in offspring obtained from 29 matings involving either females or males heterozygous at both loci. No recombinants were found among 303 offspring bred from 6 heterozygous males, whereas 160 were parental and 138 were recombinants among 298 offspring bred from 9 heterozygous females. The recombination frequency was 46.3%. These results show that the sex difference when two loci were recombined was marked and significant inRana japonica.     

Biosynthetic relations between protoberberine-, benzo(C)phenanthridine- and B-secoprotoberberine type alkaloids in Corydalis incisa

The biosynthetic relations between protoberberine-, benzo[C]phenanthridine- and B-secoprotoberberine type alkaloids were demonstrated by use of (±)-tetrahydrocoptisine-[8,14-³H HCl, (±)-tetrahydrocorysamine-[8,14-³H]HCl and corynoline-[6-³H]HCl in Corydalis incisa, and the following results were presented. (±)-Tetrahydrocoptisine was converted to corynoline, corydalic acid methyl ester and corydamine hydrochloride. (±)-Tetrahydrocorysamine was converted to corynoline and corydalic acid methyl ester. Evidence that N-methyl-3-[6′-(3′,4′-methylenedioxyphenethylalcohol)]-4-methyl-7,8-methylenedioxy-1,2,3,4-tetrahydroisoquinoline-[α-³H] HCl was incorporated into corynoline-[11-³H] indicates the occurrence of the ring fission at C₆-N followed by linking ofthe C₆ and C₁₃ positions in (±)-tetrahydrocoptisine and (±)-tetrahydrocorysamine, and suggests the participation of one of two possible intermediates in the biosynthesis of these alkaloids.     

Two types of mouse (Mus musculus domesticus) Y chromosomes in Quebec.

A Y chromosomal repetitive sequence identified two types of Y chromosomes in mice (Mus musculus domesticus) caught near Ste. Anne de Bellevue, Quebec. One type is apparently identical to the Y chromosome found in Maryland, Delaware, and California, whereas the other type is similar, but not identical, to the Y chromosome present in M.m. poschiavinus, an Alpine race of M.m. domesticus. These findings suggest that the domesticus Y chromosome is highly polymorphic and thus useful for elucidating the relationships among American and European house mouse populations.     

Three secoiridoid glucosides from Ligustrum japonicum

Three new secoiridoid glucosides, ligustaloside A, ligustaloside B and 10-hydroxyoleuropein, along with two known glucosides, oleuropein and ligstrosid     

Induction of the cortical reaction in isolated sea urchin egg cortices: effects of Ca2+ and ionophore A23187

The cortical reaction in isolated sea urchin (Strongylocentrotus purpuratus) egg cortices has been monitored with phase-contrast video microscopy. It was confirmed that the cortical reaction is induced by exposure to Ca2+. No induction was observed after exposure to the Ca2+-ionophore A23187, although the cortices remain sensitive to a subsequent exposure to Ca2+, and the cortical reaction in unfertilized eggs suspended in cortex isolation medium remains inducible by exposure to A23187. These results imply: (1) that A23187 does not induce the cortical reaction directly; (2) that the release of intracellular Ca2+, through which A23187 induces the cortical reaction, is not from storage sites localized entirely in the cortex; and (3) that intracellular storage sites for the Ca2+ involved in the cortical reaction are also present outside the cortex.     

Costimulation via glucocorticoid-induced TNF receptor in both conventional and CD25+ regulatory CD4+ T cells

The glucocorticoid-induced TNF receptor (GITR), which is a member of the TNF receptor family, is expressed preferentially at high levels on CD25+CD4+ regulatory T cells and plays a key role in the peripheral tolerance that is mediated by these cells. GITR is also expressed on conventional CD4+ and CD8+ T cells, and its expression is enhanced rapidly after activation. In this report we show that the GITR provides a potent costimulatory signal to both CD25+ and CD25- CD4+ T cells. GITR-mediated stimulation induced by anti-GITR mAb DTA-1 or GITR ligand transfectants efficiently augmented the proliferation of both CD25-CD4+ and CD25+CD4+ T cells under the limited dose of anti-CD3 stimulation. The augmentation of T cell activation was further confirmed by the enhanced cell cycle progression; early induction of the activation Ags, CD69 and CD25; cytokine production, such as IL-2, IFN-gamma, IL-4, and IL-10; anti-CD3-induced redirected cytotoxicity; and intracellular signaling, assessed by translocation of NF-kappaB components. GITR costimulation showed a potent ability to produce high amounts of IL-10, which resulted in counter-regulation of the enhanced proliferative responses. Our results highlight evidence that GITR acts as a potent and unique costimulator for an early CD4+ T cell activation.     

Synthesis and inhibition mechanism of Delta lac-acetogenins, a novel type of inhibitor of bovine heart mitochondrial complex I

We have synthesized Deltalac-acetogenins that are new acetogenin mimics possessing two n-alkyl tails without an alpha,beta-unsaturated gamma-lactone ring and suggested that their inhibition mechanism may be different from that of common acetogenins [Hamada et al. (2004) Biochemistry 43, 3651-3658]. To elucidate the inhibition mechanism of Deltalac-acetogenins in more detail, we carried out wide structural modifications of original Deltalac-acetogenins and characterized the inhibitory action with bovine heart mitochondrial complex I. In contrast to common acetogenins, both the presence of adjacent bis-THF rings and the stereochemistry around the hydroxylated bis-THF rings are important structural factors required for potent inhibition. The inhibitory potency of a derivative possessing an n-butylphenyl ether structure (compound 7) appeared to be superior to that of the original Deltalac-acetogenins and equivalent to that of bullatacin, one of the most potent natural acetogenins. Double-inhibitor titration of steady-state complex I activity showed that the extent of inhibition of compound 7 and bullatacin is not additive, suggesting that the binding sites of the two inhibitors are not identical. Competition tests using a fluorescent ligand indicated that the binding site of compound 7 does not overlap with that of other complex I inhibitors. The effects of compound 7 on superoxide production from complex I are also different from those of other complex I inhibitors. Our results clearly demonstrate that Deltalac-acetogenins are a novel type of inhibitor acting at the terminal electron-transfer step of bovine complex I.     

LIGAND: chemical database of enzyme reactions

LIGAND is a composite database comprising three sections: ENZYME for the information of enzyme molecules and enzymatic reactions, COMPOUND for the information of metabolites and other chemical compounds, and REACTION for the collection of substrate-product relations. The current release includes 3390 enzymes, 5645 compounds and 5207 reactions. The database is indispensable for the reconstruction of metabolic pathways in the completely sequenced organisms. The LIGAND database can be accessed through the WWW (http://www.genome.ad.jp/dbget/ligand.html ) or may be downloaded by anonymous FTP (ftp://kegg.genome.ad.jp/molecules/ligand/ ).