Metabolism of trans, trans-muconaldehyde by aldehyde and alcohol dehydrogenases: Identification of a novel metabolite

Goon, Daniel Ter; Cheng, Xiaoqin; Ruth, James A.; Petersen, Dennis R.; Ross, David

doi:10.1016/0041-008x(92)90107-4

Cited by 32 publications

(26 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Detection of HHA as a metabolite of MUC in vivo extends observations made in vitro (8,9). Detection of HI-IA in urine of benzene-treated animals is consistent with the hypothesis that benzene is metabolized in vivo to ring-opened metabolites via MUC (Fig.…”

supporting

confidence: 71%

“…Conver (9). However, HAl is not converted to MA in these systems (8,9). Another MUC analogue, the carboxylic acid aldehyde (AAI; Table 1) is metabolized to MA and to a small amount of HHA by mouse liver cytosol (9).…”

mentioning

confidence: 99%

“…Muconaldehyde has not been directly detected in animals dosed with benzene, presumably due to its reactivity. In vitro, MUC is metabolized to a number of oxidized and reduced products of which MA and 6-hydroxy-trans, trans-hexadienoic acid (HHA, Table 1) are stable end products (8,9). We previously established that MUC is metabolized in vivo to MA (10).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Identification of 6-hydroxy-trans,trans-2,4-hexadienoic acid, a novel ring-opened urinary metabolite of benzene.

Kline

Robertson

Grotz

et al. 1993

Environ Health Perspect

View full text Add to dashboard Cite

We studied the in vivo metabolism of benzene in mice to ring-opened compounds excreted in urine. Male CD-1 mice were treated intraperitoneally with benzene (110-440 mg/kg), [14C]benzene (220 mg/kg) or trans, trans-muconaldehyde (MUC; 4 mg/kg), a microsomal, hematotoxic metabolite of benzene. Urine, collected over 24 hr, was extracted and analyzed by HPLC with a diode-array detector and by scintillation counting. In addition to trans,trans-muconic acid, previously the only known ring-opened urinary benzene metabolite, a new metabolite, 6-hydroxy-trans,trans-2,4-hexadienoic acid, was detected in urine of mice treated with either benzene or MUC. We identified the new metabolite based on coelution of metabolites and UV spectral comparison with authentic standards in unmethylated and methylated urine extracts. Results presented here are consistent with the intermediacy of MUC in the in vivo metabolism of benzene to ring-opened metabolites. Images p310-a

show abstract

supporting

confidence: 71%

mentioning

confidence: 99%

See 1 more Smart Citation

Identification of 6-hydroxy-trans,trans-2,4-hexadienoic acid, a novel ring-opened urinary metabolite of benzene.

Kline

Robertson

Grotz

et al. 1993

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…(9). The same compounds were also reported to be end products of muconaldehyde metabolism in rat liver hepatocytes (8). Studies with mouse liver cytosol showed that the formation of CHO-M-OH from MUC is reversible (9).…”

Section: Formation Of Ring-opened Metabolites Of Benzenementioning

confidence: 87%

“…This narrow window of toxicity may be caused by saturation of the detoxification metabolism of CHO-M-OH. At a low dose, most of CHO-M-OH may be metabolized to COOH-M-OH, a stable MUC metabolite (8,9). At a high dose, this pathway may be saturated; therefore, more CHO-M-OH is oxidized back to MUC (9), which is hematotoxic in mice at 2 mg/kg/day (23).…”

Section: Formation Of Ring-opened Metabolites Of Benzenementioning

confidence: 99%

Reactive Ring-Opened Aldehyde Metabolites in Benzene Hematotoxicity

Witz¹,

Zhang²,

Goldstein³

1996

Environmental Health Perspectives

View full text Add to dashboard Cite

The aldehydic MUC metabolite 6-hydroxy-trans-trans-2,4-hexadienal (CHO-M-OH), similar to MUC but to a lesser extent, is reactive toward glutathione, mutagenic in V79 cells, and hematotoxic in mice. It is formed by monoreduction of MUC, a process that is reversible and could be of biological significance in benzene bone marrow toxicity. The MUC metabolite 6-hydroxy-trans-trans-2,4-hexadienoic (COOH-M-OH) is an end product of MUC metabolism in vitro. Our studies indicate that COOH-M-OH is a urinary metabolite of benzene in mice, a finding that provides further indirect evidence for the in vivo formation of MUC from benzene. Mechanistic studies showed the formation of cis-trans-muconaldehyde in addition to MUC from benzene incubated in a hydroxyl radical-generating Fenton system. These results suggest that the benzene ring is initially opened to cis,cis-muconaldehyde, an unstable isomer that rearranges to cis-trans-muconaldehyde, which further rearranges to trans-trans-muconaldehyde. The latter is not formed from benzene dihydrodiol by reactive oxygen species in a Fenton system that contains reactive oxygen species.

show abstract

Benzene

Goldstein

Witz

2008

Environmental Toxicants

View full text Add to dashboard Cite

Metabolism of trans, trans-muconaldehyde by aldehyde and alcohol dehydrogenases: Identification of a novel metabolite

Cited by 32 publications

References 18 publications

Identification of 6-hydroxy-trans,trans-2,4-hexadienoic acid, a novel ring-opened urinary metabolite of benzene.

Identification of 6-hydroxy-trans,trans-2,4-hexadienoic acid, a novel ring-opened urinary metabolite of benzene.

Reactive Ring-Opened Aldehyde Metabolites in Benzene Hematotoxicity

Benzene

Contact Info

Product

Resources

About