Isoflavones Inhibit Nicotine <i>C</i>‐Oxidation Catalyzed by Human CYP2A6

Nakajima, Miki; Itoh, Tatsuki; Yamanaka, Hidetoshi; Fukami, Tatsuki; Tokudome, Shogo; Yamamoto, Yasuhiko; Yamamoto, Hiroshi; Yokoi, Tsuyoshi

doi:10.1177/0091270005285199

Cited by 28 publications

(17 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genetic polymorphisms of CYP2A6 gene can explain the interindividual variability, but our recent study revealed that considerable variability was still observed among homozygotes of the wild CYP2A6 allele (Nakajima et al, 2006a). Three possible reasons for the variability are inferred: 1) the expression level of CYP2A6 varies, possibly owing to differences in transcriptional or post-transcriptional regulation; 2) dietary and/or environmental compounds may affect the enzymatic activity, as we recently reported that dietary isoflavones inhibit nicotine C-oxidation (Nakajima et al, 2006c); and 3) endogenous compounds may affect the enzymatic activity. In the present study, to examine the third possibility, the inhibitory …”

Section: Discussionmentioning

confidence: 98%

Inhibitory Effects of Neurotransmitters and Steroids on Human CYP2A6

Higashi

Nakajima²,

Katoh³

et al. 2007

Drug Metab Dispos

Self Cite

View full text Add to dashboard Cite

ABSTRACT:Human CYP2A6 catalyzes the metabolism of nicotine, cotinine, and coumarin as well as some pharmaceutical drugs. CYP2A6 is highly expressed in liver and, also, in brain and steroid-related tissues. In this study, we investigated the inhibitory effects of neurotransmitters and steroid hormones on CYP2A6 activity. We found that coumarin 7-hydroxylation and cotinine 3-hydroxylation by recombinant CYP2A6 expressed in baculovirus-infected insect cells were competitively inhibited by tryptamine (both Thus, we found that some neurotransmitters inhibit CYP2A6 activity, being related with inter-and intraindividual differences in CYP2A6-dependent metabolism. The inhibitory effects of steroid hormones on aldehyde oxidase may also contribute to interindividual differences in nicotine metabolism.

show abstract

Section: Discussionmentioning

confidence: 98%

Inhibitory Effects of Neurotransmitters and Steroids on Human CYP2A6

Higashi

Nakajima²,

Katoh³

et al. 2007

Drug Metab Dispos

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, CYP catalyzed the formation of genistein from biochanin A [85,86]. In animals and humans, this demethylation reaction has been detected following red clover and kaempferol administrations [87][88][89].…”

Section: Other Metabolic Pathwaysmentioning

confidence: 99%

Natural polyphenol disposition via coupled metabolic pathways

Liu¹,

Hu²

2007

Expert Opinion on Drug Metabolism & Toxicology

126

View full text Add to dashboard Cite

A major challenge associated with the development of chemopreventive polyphenols is the lack of bioavailability in vivo, which are primarily the result of coupled metabolic activities of conjugating enzymes and efflux transporters. These coupling processes are present in most of tissues and organs in mammals and are efficient for the purposes of drug metabolism, elimination and detoxification. Therefore, it was expected that these coupling processes represent a significant barrier to the oral bioavailabilities of polyphenols. In various studies of this coupling process, it was identified that various conjugating enzymes such as UGT and SULT are capable of producing very hydrophilic metabolites of polyphenols, which cannot diffuse out of the cells and needs the action of efflux transporters to pump them out of the cells. Additional studies have shown that efflux transporters such as MRP2, BCRP and OAT appear to serve as the gate keeper when there is an excess capacity to metabolize the compounds. These efflux transporters may also act as the facilitator of metabolism when there is a product/metabolite inhibition. For polyphenols, these coupled processes enable a duo recycling scheme of enteric and enterohepatic recycling, which allows the polyphenols to be reabsorbed and results in longer than expected apparent plasma half-lives for these compounds and their conjugates. Since the vast majority of polyphenols in plasma are hydrophilic conjugates, more research is needed to determine if the metabolites are active or reactive, which will help explain their mechanism of actions.

show abstract

“…Previously, isoflavones (Nakajima et al, 2006), menthol (MacDougall et al, 2003;Kramlinger et al, 2012), menthofuran (Khojasteh-Bakht et al, 1998), isothiocyanates (Nakajima et al, 2001;von Weymarn et al, 2007), and several others (Di et al, 2009) were studied and found to inhibit CYP2A6. Based on the structural and biophysical studies of CYP2A6, low-molecular-weight phenylpropanoids, such as t-CA (Fig.…”

Section: Introductionmentioning

confidence: 99%

Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole

Chan¹,

Oshiro²,

Thomas³

et al. 2016

Drug Metabolism and Disposition

View full text Add to dashboard Cite

Human exposure to trans-cinnamic aldehyde [t-CA; cinnamaldehyde; cinnamal; (E)-3-phenylprop-2-enal] is common through diet and through the use of cinnamon powder for diabetes and to provide flavor and scent in commercial products. We evaluated the likelihood of t-CA to influence metabolism by inhibition of P450 enzymes. IC 50 values from recombinant enzymes indicated that an interaction is most probable for CYP2A6 (IC 50 = 6.1 mM). t-CA was 10.5-fold more selective for human CYP2A6 than for CYP2E1; IC 50 values for P450s 1A2, 2B6, 2C9, 2C19, 2D6, and 3A4 were 15.8-fold higher or more. t-CA is a type I ligand for CYP2A6 (K S = 14.9 mM). Inhibition of CYP2A6 by t-CA was metabolism-dependent; inhibition required NADPH and increased with time. Glutathione lessened the extent of inhibition modestly and statistically significantly. The carbon monoxide binding spectrum was dramatically diminished after exposure to NADPH and t-CA, suggesting degradation of the heme or CYP2A6 apoprotein. Using a static model and mechanism-based inhibition parameters (K I = 18.0 mM; k inact = 0.056 minute 21

show abstract

Isoflavones Inhibit Nicotine C‐Oxidation Catalyzed by Human CYP2A6

Cited by 28 publications

References 30 publications

Inhibitory Effects of Neurotransmitters and Steroids on Human CYP2A6

Inhibitory Effects of Neurotransmitters and Steroids on Human CYP2A6

Natural polyphenol disposition via coupled metabolic pathways

Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole

Contact Info

Product

Resources

About