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Chemical Compound Review:

CHEMBL17416 4-hydroxy-1-pyridin-3-yl- butan-1-one

Synonyms: AG-G-12400, SureCN2945748, CTK5B0161, ZINC02047388, AR-1G2594, ...

Trushin, N. et al., Smith, T.J. et al., Zwickenpflug, W. et al., Kutzer, C. et al., Hecht, S.S. et al., et al.

Zwickenpflug, Tyroller,

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High impact information on 4-HPB

These adducts release 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) upon hydrolysis [1].
4-Hydroxy-1-(3-pyridyl)-1-butanone-releasing adducts were also detected in the nasal mucosa DNA of the rats treated with NNN [2].
In the rats treated with [4,4-D2]NNK, levels of O6-methylguanine in DNA from both the olfactory and respiratory portions of the nasal mucosa were significantly lower and levels of 4-hydroxy-1-(3-pyridyl)-1-butanone-releasing DNA adducts higher than in the rats treated with equivalent doses of the less carcinogenic compounds NNK or [CD3]NNK [2].
Approximately 1 pmol of AGT was inhibited for every 25 to 50 pmol of 4-hydroxy-1-(3-pyridyl)-1-butanone- releasing adducts present in NNKOAc-treated DNA [3].
In rats treated with [5-3H]NNK, 20 to 40% of the tritium bound to hemoglobin (Hb) is released by base hydrolysis as 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) [4].

Biological context of 4-HPB

At intervals during the study, blood was withdrawn from selected rats, and 4-hydroxy-1-(3-pyridyl)-1-butanone-releasing hemoglobin adducts, which are formed upon metabolic activation of NNK, were quantified [5].
Upon nitrosation, myosmine yields 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) and N-nitrosonornicotine (NNN) [J. Agric. Food Chem. 48 (2001) 392] [6].

Anatomical context of 4-HPB

Our previous study demonstrated that cytochrome P450 (P450) 1A2 catalyzes the formation of 4-hydroxy-1-(3-pyridyl)-1-butanone (keto alcohol) (an alpha-hydroxylation product) from NNK in human liver microsomes [7].
Cultured rat esophagus metabolized (S)-NNN (1 microM) predominantly to products of 2'-hydroxylation, 4-oxo-4-(3-pyridyl)butanoic acid (keto acid) and 4-hydroxy-1-(3-pyridyl)-1-butanone (keto alcohol) [8].

Associations of 4-HPB with other chemical compounds

3-Pyridylacetic acid, 4-oxo-4-(3-pyridyl)butanoic acid (keto acid), 3-pyridylmethanol, 3'-hydroxymyosmine, and 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) have been identified as urinary metabolites after oral administration to female Wistar rats [9].

Gene context of 4-HPB

After mild base-catalysed hydrolysis releasing aromatic amines and the TSNA adduct 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB), the extraction, cleanup, and concentration are performed by a one-step procedure using C18 cartridges [10].

Analytical, diagnostic and therapeutic context of 4-HPB

4-Hydroxy-1-(3-pyridyl)-1-butanone-hemoglobin adducts as biomarkers of exposure to tobacco smoke: validation of a method to be used in multicenter studies [11].

References

Biomarkers for human uptake and metabolic activation of tobacco-specific nitrosamines. Hecht, S.S., Carmella, S.G., Foiles, P.G., Murphy, S.E. Cancer Res. (1994) [Pubmed]
Evidence supporting the role of DNA pyridyloxobutylation in rat nasal carcinogenesis by tobacco-specific nitrosamines. Trushin, N., Rivenson, A., Hecht, S.S. Cancer Res. (1994) [Pubmed]
Pyridyloxobutyl DNA adducts inhibit the repair of O6-methylguanine. Peterson, L.A., Liu, X.K., Hecht, S.S. Cancer Res. (1993) [Pubmed]
Two types of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone hemoglobin adducts, from metabolites which migrate into or are formed in red blood cells. Murphy, S.E., Coletta, K.A. Cancer Res. (1993) [Pubmed]
Complete inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced rat lung tumorigenesis and favorable modification of biomarkers by phenethyl isothiocyanate. Hecht, S.S., Trushin, N., Rigotty, J., Carmella, S.G., Borukhova, A., Akerkar, S., Rivenson, A. Cancer Epidemiol. Biomarkers Prev. (1996) [Pubmed]
Nitrosation of dietary myosmine as risk factor of human cancer. Wilp, J., Zwickenpflug, W., Richter, E. Food Chem. Toxicol. (2002) [Pubmed]
Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by human cytochrome P450 1A2 and its inhibition by phenethyl isothiocyanate. Smith, T.J., Guo, Z., Guengerich, F.P., Yang, C.S. Carcinogenesis (1996) [Pubmed]
Metabolism of N'-nitrosonornicotine enantiomers by cultured rat esophagus and in vivo in rats. McIntee, E.J., Hecht, S.S. Chem. Res. Toxicol. (2000) [Pubmed]
Reaction of the tobacco alkaloid myosmine with hydrogen peroxide. Zwickenpflug, W., Tyroller, S. Chem. Res. Toxicol. (2006) [Pubmed]
Simultaneous solid-phase extraction and gas chromatographic-mass spectrometric determination of hemoglobin adducts from tobacco-specific nitrosamines and aromatic amines. Kutzer, C., Branner, B., Zwickenpflug, W., Richter, E. Journal of chromatographic science. (1997) [Pubmed]
4-Hydroxy-1-(3-pyridyl)-1-butanone-hemoglobin adducts as biomarkers of exposure to tobacco smoke: validation of a method to be used in multicenter studies. Atawodi, S.E., Lea, S., Nyberg, F., Mukeria, A., Constantinescu, V., Ahrens, W., Brueske-Hohlfeld, I., Fortes, C., Boffetta, P., Friesen, M.D. Cancer Epidemiol. Biomarkers Prev. (1998) [Pubmed]

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