Isolation and some properties of dioxygenase and co-oxidase activities of adult human liver cytosolic lipoxygenase

Metabolic fate of chemical mixtures. I. ?Shuttle oxidant? effect of lipoxygenase-generated radical of chlorpromazine and related phenothiazines on the oxidation of benzidine and other xenobiotics

“…More recently, the generation of BZ diimine cation, another reactive metabolite of BZ capable of covalent binding to macromolecules [51][52][53], by the cytoplasmic LO activity was proposed as an alternate bioactivation pathway for the hepatocarcinogenesis in the rat [54]. Similar results were noted with purified human liver LO [55]. For bladder cancer, it is proposed that the liver converts N-acetyl BZ to its N-glucuronide, which is transported via blood to the kidney [44].…”

Metabolic fate of chemical mixtures. I. ?Shuttle oxidant? effect of lipoxygenase-generated radical of chlorpromazine and related phenothiazines on the oxidation of benzidine and other xenobiotics

“…More recently, the generation of BZ diimine cation, another reactive metabolite of BZ capable of covalent binding to macromolecules [51][52][53], by the cytoplasmic LO activity was proposed as an alternate bioactivation pathway for the hepatocarcinogenesis in the rat [54]. Similar results were noted with purified human liver LO [55]. For bladder cancer, it is proposed that the liver converts N-acetyl BZ to its N-glucuronide, which is transported via blood to the kidney [44].…”

N-dealkylation of aminopyrine catalyzed by soybean lipoxygenase in the presence of hydrogen peroxide

“…Although other enzymes were not considered, we believe that it is possible that the differences noted may be related, at least in part, to the metabolism of aminopyrine via the lipoxygenase pathway. This contention is supported by the observations that lipoxygenase activity is plentiful in the rat (51) and human (47,52) liver, and other tissues (1). Furthermore, it has been documented that similar to SLO, the human tissue enzyme is capable of mediating xenobiotic oxidation in the presence of H 2 O 2 (30).…”

Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals

“…Rodent embryonic LO activity can mediate this bioactivation of benzidine [93]. Purified LO from human term placenta [104], conceptal tissues at 10 weeks of gestation [98], adult human lung [136] and liver [137] also catalyze this reaction. Collectively, these results suggest that benzidine may be a developmental toxicant in man.…”

“…LO inhibitors and free radical scavengers markedly decrease the rate of SLO-mediated GS-PAP formation. Since significant LO activity occurs in rat [221] and human [137,147] liver as well as in rat embryo [93] and human conceptal tissues [96][97][98], in vivo teratogenic bioactivation of PAP by LO can be expected. In contrast to rat embryos which lack GST [222], human term placenta [223][224][225][226], human intrauterine conceptal tissues during early pregnancy (6-10 weeks gestation) [226] and human fetal liver (16-18 weeks gestation) [227][228][229][230] contain relatively high titer of this enzyme.…”

Metabolic fate of chemical mixtures. I. ?Shuttle oxidant? effect of lipoxygenase-generated radical of chlorpromazine and related phenothiazines on the oxidation of benzidine and other xenobiotics

“…More recently, the generation of BZ diimine cation, another reactive metabolite of BZ capable of covalent binding to macromolecules [51][52][53], by the cytoplasmic LO activity was proposed as an alternate bioactivation pathway for the hepatocarcinogenesis in the rat [54]. Similar results were noted with purified human liver LO [55]. For bladder cancer, it is proposed that the liver converts N-acetyl BZ to its N-glucuronide, which is transported via blood to the kidney [44].…”

N-dealkylation of aminopyrine catalyzed by soybean lipoxygenase in the presence of hydrogen peroxide

“…Although other enzymes were not considered, we believe that it is possible that the differences noted may be related, at least in part, to the metabolism of aminopyrine via the lipoxygenase pathway. This contention is supported by the observations that lipoxygenase activity is plentiful in the rat (51) and human (47,52) liver, and other tissues (1). Furthermore, it has been documented that similar to SLO, the human tissue enzyme is capable of mediating xenobiotic oxidation in the presence of H 2 O 2 (30).…”

Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals

“…Rodent embryonic LO activity can mediate this bioactivation of benzidine [93]. Purified LO from human term placenta [104], conceptal tissues at 10 weeks of gestation [98], adult human lung [136] and liver [137] also catalyze this reaction. Collectively, these results suggest that benzidine may be a developmental toxicant in man.…”

“…LO inhibitors and free radical scavengers markedly decrease the rate of SLO-mediated GS-PAP formation. Since significant LO activity occurs in rat [221] and human [137,147] liver as well as in rat embryo [93] and human conceptal tissues [96][97][98], in vivo teratogenic bioactivation of PAP by LO can be expected. In contrast to rat embryos which lack GST [222], human term placenta [223][224][225][226], human intrauterine conceptal tissues during early pregnancy (6-10 weeks gestation) [226] and human fetal liver (16-18 weeks gestation) [227][228][229][230] contain relatively high titer of this enzyme.…”

Metabolic fate of chemical mixtures. I. ?Shuttle oxidant? effect of lipoxygenase-generated radical of chlorpromazine and related phenothiazines on the oxidation of benzidine and other xenobiotics

“…More recently, the generation of BZ diimine cation, another reactive metabolite of BZ capable of covalent binding to macromolecules [51][52][53], by the cytoplasmic LO activity was proposed as an alternate bioactivation pathway for the hepatocarcinogenesis in the rat [54]. Similar results were noted with purified human liver LO [55]. For bladder cancer, it is proposed that the liver converts N-acetyl BZ to its N-glucuronide, which is transported via blood to the kidney [44].…”

N-dealkylation of aminopyrine catalyzed by soybean lipoxygenase in the presence of hydrogen peroxide

“…Although other enzymes were not considered, we believe that it is possible that the differences noted may be related, at least in part, to the metabolism of aminopyrine via the lipoxygenase pathway. This contention is supported by the observations that lipoxygenase activity is plentiful in the rat (51) and human (47,52) liver, and other tissues (1). Furthermore, it has been documented that similar to SLO, the human tissue enzyme is capable of mediating xenobiotic oxidation in the presence of H 2 O 2 (30).…”

Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals

“…Rodent embryonic LO activity can mediate this bioactivation of benzidine [93]. Purified LO from human term placenta [104], conceptal tissues at 10 weeks of gestation [98], adult human lung [136] and liver [137] also catalyze this reaction. Collectively, these results suggest that benzidine may be a developmental toxicant in man.…”

“…LO inhibitors and free radical scavengers markedly decrease the rate of SLO-mediated GS-PAP formation. Since significant LO activity occurs in rat [221] and human [137,147] liver as well as in rat embryo [93] and human conceptal tissues [96][97][98], in vivo teratogenic bioactivation of PAP by LO can be expected. In contrast to rat embryos which lack GST [222], human term placenta [223][224][225][226], human intrauterine conceptal tissues during early pregnancy (6-10 weeks gestation) [226] and human fetal liver (16-18 weeks gestation) [227][228][229][230] contain relatively high titer of this enzyme.…”