Phosgene: a possible role in the potentiation of carbon tetrachloride hepatotoxicity by 2-propanol

The metabolism of carbon tetrachloride to chloroform, carbon monoxide, carbon dioxide, and phosgene, as well as carbon tetrachloride-induced lipid peroxidation was studied in control, 2-propanol-, and phenobarbital-treated rats. Different effects were observed following 2-propanol and phenobarbital treatments. 2-Propanol treatment increased phosgene formation but had no effect on carbon tetrachloride-induced lipid peroxidation, while phenobarbital treatment had no effect on phosgene formation and potentiated carbon tetrachloride-induced lipid peroxidation. These data suggest that 2-propanol and phenobarbital treatments alter either the activity or composition of constitutive forms of cytochrome P-450 responsible for the metabolism of carbon tetrachloride and, in addition, suggest that phosgene may play a role in 2-propanol potentiation of carbon tetrachloride hepatotoxicity.     

Caffeine: also a fungal metabolite

Caffeine has been found to occur as a fungal metabolite and to be the principal alkaloid in sclerotia of Claviceps sorghicola, a Japanese ergot pathogen of Sorghum spp.     

Fumarate: Multiple functions of a simple metabolite

Although much is now known about fumarate metabolism, our knowledge of some aspects of its biological function remain far from comprehensive. In this short review we begin with an introductory overview of the role of fumarate in both plant and non-plant systems. We next highlight the relative importance of fumarate in relation to cell type and circumstance in contrast to other chemically similar organic acids. Considerable cumulative evidence is suggestive of a role for fumarate in pH regulation during nitrate assimilation and that fumarate has similar effects as malate during stomatal movement. Indeed it is currently difficult to separate the biological function of fumarate from malate under certain circumstances. However, in other cases this can be easily performed. This physiological complexity notwithstanding it remains possible that the engineering of fumarate metabolism may provide opportunities to improve plant growth and performance.     

MathDAMP: a package for differential analysis of metabolite profiles

Background  

With the advent of metabolomics as a powerful tool for both functional and biomarker discovery, the identification of specific differences between complex metabolite profiles is becoming a major challenge in the data analysis pipeline. The task remains difficult, given the datasets' size, complexity, and common shifts in migration (elution/retention) times between samples analyzed by hyphenated mass spectrometry methods.     

Riboflavin- and cobalamin-mediated biodegradation of chloroform in a methanogenic consortium

Chloroform (CF) is an important priority pollutant contaminating groundwater. Reductive dechlorination by anaerobic microorganisms is a promising strategy towards the remediation of CF. The objective of this study was to evaluate the use of redox active vitamins as electron shuttles to enhance the anaerobic biodegradation of CF in an unadapted methanogenic consortium not previously exposed to chlorinated compounds. Only negligible degradation of CF was observed in control cultures lacking redox active vitamins. The addition of riboflavin (RF), cyanocobalamin (CNB12), and hydroxycobalamin (HOB12) enabled biodegradation of CF. The reactions were predominantly catalyzed biologically as evidenced by the lack of any CF conversion in heat-killed controls amended with the cobalamins or minor conversion with RF. In live cultures, significant increases in the rate of CF conversion was observed at substoichiometric molar ratios as low as 0.1 to 0.01 vitamin:CF for RF and CNB12, respectively. At the highest molar vitamin:CF ratios tested of 0.2, the first-order rate constant of CF degradation was 5.3- and 91-fold higher in RF and CNB12 amended cultures, respectively, compared to the unamended control culture. The distribution of biotransformation products was highly impacted by the type of redox active vitamin utilized. Cultures supplemented with RF provided high yields of dichloromethane (DCM). On the other hand, cobalamins promoted the near complete mineralization of organochlorine in CF to inorganic chloride and lowered the yield of DCM. In cultures where no or little CF bioconversion occurred, prolonged exposure to CF resulted in cell lysis, as evidenced by the release of intracellular chloride. The results taken as a whole suggest that the anaerobic bioremediation of CF-contaminated sites can greatly be improved with strategies aimed at increasing the concentration of redox active vitamins.     

Solubility of phosphatidylcholine in chloroform. Formation of hydrogen bonding between phosphatidylcholine and chloroform

The solubility of phosphatidylcholine (PC) was studied by the spectroscopic analysis and the measurement of the solubility. The qualitative analysis of infrared absorptionspectra confirmed the existence of two types of hydrogen bondings between chloroform and PC, one between chloroform and the CO group of PC and the other between chloroform and the phosphorylcholine group of PC. The quantitative analysiss of the C6 stretching vibration bands of the chloroform-d solution of PC showed that the latter hydrogen bonding mainly contributes to the solubility and that PC dissolves in chloroform to form a complex consisting of a few or more molecules of chloroform and one molecule of PC. We discussed in this report about the molecular organization of PC in chloroform solution.     

Norcocaine: a pharmacologically active metabolite of cocaine found in brain

N-Demethylation of cocaine results in the production of norcocaine, which has been identified by gas chromatography-mass spectrometry in the brains of monkeys given repeated doses of cocaine. This metabolite is about as active as cocaine in inhibiting uptake of ³H-norepinephrine by synaptosomes prepared from rat brain. Other cocaine derivatives have been found to be relatively inactive in inhibiting uptake of this amine.     

2-fluoro-ATP: a toxic metabolite of 9-beta-D-arabinosyl-2-fluoroadenine

Murine P388 cells incubated in vitro with the anticancer drug arabinosyl 2-fluoroadenine accumulate its 5'-triphosphate, F-araATP, as the major phosphorylated metabolite. A new chromatographically separate metabolite that accumulated to levels 10% of that of F-araATP was identified as 2-fluoro-ATP, by the following criteria. 1. The metabolite coeluted with the authentic compound on anion-exchange HPLC. 2. Dephosphorylation of the metabolite yielded a compound that was chromatographically identical to 2-fluoroadenosine. 3. The compound was sensitive to NaIO4 oxidation. Cellular incubation experiments indicated that 2-fluoroadenine, but not arabinosyl 2-fluorohypoxanthine, was the likely intermediate in the formation of 2-fluoro-ATP.     

Tumor promoter chloroform is a potent protein kinase C activator

The major interaction site for tumor-promoting phorbol esters is the calcium-activated, phospholipid-dependent protein kinase (protein kinase C), a key-element in signal transduction. Binding of phorbol esters results in enzyme activation which mediates, at least in part, the action of these agents. We have investigated the effects of tumor promoter chloroform on protein kinase C activity. Like thrombin and 12-O-tetradecanoylphorbol-13-acetate (TPA), chloroform was able to activate protein kinase C in intact rabbit platelets. In addition, chloroform stimulated enzyme activity as well as TPA binding capacity in cell-free system. Scatchard analysis of the data has shown that chloroform increased the number of phorbol ester binding sites. Structurally related compounds, carbon tetrachloride and methylene chloride, activated the enzyme similarly.     

Metabolism of a DDT metabolite via a chloroepoxide

The 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) metabolic intermediate 1-chloro-2,2-bis(p-chlorophenyl)ethene (DDMU) is partially metabolized in vivo by mice to 2-hydroxy-2,2-bis(p-chlorophenyl)acetic acid (αOH-DDA) and other metabolites which are excreted in urine. The subsequent DDT metabolic intermediates 1-chloro-2,2-bis(p-chlorophenyl)ethane (DDMS) and 1,1-bis(p-chlorophenyl)ethene (DDNU) are metabolized to αOH-DDA to a much lesser extent. These results imply that DDMU may be metabolized via an α-chloroepoxide. The authentic DDMU-epoxide, which after oral administration is excreted as αOH-DDA, is mutagenic in the Ames assay, and thermally rearranges rapidly to the corresponding α-chloroaldehyde, 2,2-bis(p-chlorophenyl)-2-chloroacetaldehyde (αCl-DDCHO). As expected αCl-DDCHO yielded the same urinary metabolites as DDMU-epoxide. This suggested metabolic pathway for DDMU via a chloroepoxide intermediate may account for the tumorigenicity of DDT in mice.     

大豆素代谢产物——雌马酚研究进展

雌马酚是大豆异黄酮的主要组份之一大豆素（Dai）的代谢产物,人群中约有30％～50％能将大豆素转化为雌马酚,影响因素目前尚不完全清楚,最重要的因素是肠道菌群。雌马酚较其原型具有更为有效的生物学作用,因此受到普遍关注。研究和开发雌马酚的生物活性,在多种常见慢性病的预防与控制方面具有重要的理论和实际意义。