Glutathione-S-Crotonyl-N-Acetylthioethanolamine Alkenetransferase: Properties and Comparison with Other Glutathione-S-Transferases

<p>A mercapturic acid is an N-acetylated-S-substituted -L-cysteine in which the substitutive group is generally inert to further enzymic reaction (Wood, 1970). Detoxication of foreign compounds to mercapturic acids in mammals has been known for almost 100 years, however the source of cysteine for conjugation has only recently been positively determined.</p>

Glutathione-S-Crotonyl-N-Acetylthioethanolamine Alkenetransferase: Properties and Comparison with Other Glutathione-S-Transferases

<p>A mercapturic acid is an N-acetylated-S-substituted -L-cysteine in which the substitutive group is generally inert to further enzymic reaction (Wood, 1970). Detoxication of foreign compounds to mercapturic acids in mammals has been known for almost 100 years, however the source of cysteine for conjugation has only recently been positively determined.</p>

In Vitro and In Vivo Analysis of Ochratoxin A-Derived Glucuronides and Mercapturic Acids as Biomarkers of Exposure

Ochratoxin A (OTA) is a widespread food contaminant, with exposure estimated to range from 0.64 to 17.79 ng/kg body weight (bw) for average consumers and from 2.40 to 51.69 ng/kg bw per day for high consumers. Current exposure estimates are, however, associated with considerable uncertainty. While biomarker-based approaches may contribute to improved exposure assessment, there is yet insufficient data on urinary metabolites of OTA and their relation to external dose to allow reliable estimates of daily intake. This study was designed to assess potential species differences in phase II biotransformation in vitro and to establish a correlation between urinary OTA-derived glucuronides and mercapturic acids and external exposure in rats in vivo. In vitro analyses of OTA metabolism using the liver S9 of rats, humans, rabbits and minipigs confirmed formation of an OTA glucuronide but provided no evidence for the formation of OTA-derived mercapturic acids to support their use as biomarkers. Similarly, OTA-derived mercapturic acids were not detected in urine of rats repeatedly dosed with OTA, while indirect analysis using enzymatic hydrolysis of the urine samples prior to LC–MS/MS established a linear relationship between urinary glucuronide excretion and OTA exposure. These results support OTA-derived glucuronides but not mercapturic acids as metabolites suitable for biomonitoring.

Urinary Mercapturic Acids to Assess Exposure to Benzene and Other Volatile Organic Compounds in Coke Oven Workers

Coke production was classified as carcinogenic to humans by the International Agency for Research on Cancer. Besides polycyclic aromatic hydrocarbons, coke oven workers may be exposed to benzene and other volatile organic compounds (VOCs). The aim of this study was to assess the exposure to several VOCs in 49 coke oven workers and 49 individuals living in the same area by determining urinary mercapturic acids. Active tobacco smoking was an exclusion criterion for both groups. Mercapturic acids were investigated by a validated isotopic dilution LC-MS/MS method. Linear models were built to correct for different confounding variables. Urinary levels of N-acetyl-S-phenyl-L-cysteine (SPMA) (metabolite of benzene), N-acetyl-S-(2-hydroxy-1/2-phenylethyl)-L-cysteine (PHEMA) (metabolite of styrene), N-acetyl-S-(2-cyanoethyl)-L-cysteine (CEMA) (metabolite of acrylonitrile), N-acetyl-S-[1-(hydroxymethyl)-2-propen-1-yl)-L-cysteine and N-acetyl-S-(2-hydroxy-3-buten-1-yl)-L-cysteine (MHBMA) (metabolites of 1,3-butadiene) were 2–10 fold higher in workers than in controls (p < 0.05). For SPMA, in particular, median levels were 0.02 and 0.31 µg/g creatinine in workers and controls, respectively. Among workers, coke makers were more exposed to PHEMA and SPMA than foremen and engine operators. The comparison with biological limit values shows that the exposure of workers was within 20% of the limit values for all biomarkers, moreover three subjects exceeded the restrictive occupational limit value recently proposed by the European Chemicals Agency (ECHA) for SPMA.