• 대한한방내과학회지
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• 제34권4호
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• pp.375-383
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• 2013

Objectives : This study was performed to investigate the metabolic site of some medicinal herbs in the liver associated with CYP (Cytochrome P450). Methods : Cytochrome P450 is the major enzymes involved in drug metabolism and bioactivation. CYP3A4 and CYP2D6, the major CYP isoforms in humans, catalyse the major proportion of drugs available on the market. Scintillation proximity assay (SPA) is often used in studies to identify compounds that inhibit CYP3A4 and CYP2D6. 28 herbal extracts and radioisotopes were attached competitively to SPA beads, and followed by measuring the remaining radioisotopes in the medium. Erythromycin and dexamethasone, inhibitors of CYP3A4 and CYP2D6, were used as controls respectively. Results : Most of the 28 herbal extracts showed dose-dependent affinity to the CYP3A4 while some of the herbs showed affinity to the CYP2D6. Conclusions : These results suggest that most of the 28 herbal extracts are metabolized safely in the liver, combined with CYP3A4 and CYP2D6.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1998년도 학술발표회
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• pp.16-16
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• 1998

The role of phospholipids in the membrane binding and subsequent insertion of the microsomal protein rabbit cytochrome P450 (P450) lA2 into phospholipid bilayers was investigated. The insertion of P450 lA2 into phospholipid bilayers was determined by the amount of quenching of Trp fluorescence of P450 lA2 by pyrene and brominated and doxyl-labeled phospholipids.(omitted)

• Mass Spectrometry Letters
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• 제4권2호
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• pp.34-37
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• 2013

Honokiol and magnolol, the major bioactive neolignans of magnolia officinalis, are the most important constituents of the crude drug prescriptions that are used in the therapy of neuroses and various nervous disorders. There have been limited reports on the effects of neolignoid compounds on human cytochrome P450 activity. Therefore, the inhibitory effects of honokiol and magnolol on seven human cytochrome P450 s were evaluated in human liver microsomes. Honokiol and magnolol showed the most potent inhibition of CYP1A2-mediated phenacetin O-deethylase activity ($IC_{50}$ values of 3.5 and 5.4 mM, respectively) among the seven P450s tested. These in vitro data indicate that neolignan compounds can inhibit the activity of CYP1A2 and suggest that these compounds should be examined for potential pharmacokinetic drug interactions in vivo.

• 한국응용곤충학회지
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• 제32권2호
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• pp.225-235
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• 1993

담배나방(Heliocoverpa assulta)와 파밤나방(Spodoptera exigua)유충에 대한 유기인계 살충제인 다이아지논과 담배의 산물인 니코틴의 영향을 조사하기 위하여 본 실험을 시행하였다. 다이아지논이 처리된 담배나방유충의 사망률은 파밤나방유충의 경우보다 훨씬 높았으며 니코틴 처리구에서는 이와 반대양상을 나타내었다. 담배나방유충 중장의 cytochrome P-450 monooxygenases (MFO) 활성은 다이아지논 처리구에 비해서 니코틴 처리구에서 더욱 높게 나타났다. 담배나방유충을 기주식물인 담배잎으로 사육하였을 때 다른 화합물과는 달리 대부분의 니코틴은 변화 없이 배설되었다.

• 한국토양비료학회지
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• 제40권4호
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• pp.274-279
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• 2007

4 종류의 폐기물(생활하수오니, 공단하수오니, 피혁오니, 주정오니)과 대조구로서 돈분퇴비가 지렁이에게 미치는 독성을 평가하기 위하여 대표적인 유해성 평가 biomarker 3종류 (acetylcholinesterase, cytochrome $P_{450}$, heat shock protein 70)를 사용하였다. 유기성 폐기물에 대한 acetylcholinesterase의 활성은 돈분퇴비의 경우 활성이 약간 촉진된 반면 생활하수오니, 공단하수오니, 피혁오니, 주정오니는 영향을 미치지 않았다. Cytochrome $P_{450}$의 활성은 공단하수오니와 피혁오니는 활성을 억제하였고 생활하수오니, 주정오니, 돈분퇴비는 영향을 미치지 않았다. 또한 Hsp70의 발현량은 증류수보다 돈분퇴비는 1.9배, 주정오니는 3.0배, 생활하수오니는 3.3배, 공단오니는 4.4배, 피혁오니는 4.7배 순으로 지렁이 (Eisenia fetida)에게 스트레스를 많이 주었다. 이상의 결과로부터, 4 종류의 폐기물(생활하수오니, 공단하수오니, 피혁오니, 주정오니)은 돈분퇴비보다 독성이 강한 것으로 판단하였다. 또한 AChE, Cytochrome $P_{450}$과 Hsp70은 추후 유기성 폐기물의 유해성을 모니터링하기에 적합한 biomarker로서 가치가 있다고 생각한다.

• 생명과학회지
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• 제18권4호
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• pp.503-508
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• 2008

동해 해양심층수의 유방암예방 효능과 전이에 미치는 영향을 알아보기 위해 cytochrome P450 1A1 활성과 aromatase 활성 및 유방암세포의 침윤성, 이와 관련된 MMP-9 의 활성과 그 단백질 발현에 미치는 영향을 조사하였다. 해양심층수는 체내외의 여러 화학물질을 체내에서 활성화시켜 발암이나 돌연변이 등을 유발시키는 것으로 알려진 cytochrome P450 1A1을 경도의존적으로 저해시켰다. 또한 호르몬 의존성 유방암의 진행에 관여하는 aromatase의 활성도 경도의존적으로 저해시켰다($5.6{\sim}51.9%$). 해양심층수 처리에 의해 사람유방암세포인 MDA-MB-231 세포의 침윤성은 $73.7{\sim}29.4%$로 감소하였으며, 세포의 침윤시 작용하는 단백질 분해 효소인 MMP-9의 활성과 단백질 발현도 경도의존적으로 억제되었다. 따라서 해양심층수는 유방암 예방과 전이관련의 더 많은 연구에 의해 유방암 예방과 전이 억제작용을 증명할 수 있을 것으로 보인다.

• BMB Reports
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• 제36권3호
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• pp.332-335
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• 2003

Cytochrome P450 in microsomes can be quantitated using the characteristic 450 nm absorption peak of the CO adduct of reduced cytochrome P450. We developed a simple microplate assay method that is superior to previous methods. Our method is less laborious, suitable for analyzing many samples, and less sensitive to sample aggregation. Microsome samples in microplate wells were incubated in a CO chamber rather than bubbled with CO gas, and then reduced with sodium hydrosulfite solution. This modification allowed a reliable and reproducible assay by effectively eliminating variations between estimations.

• Journal of Microbiology and Biotechnology
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• 제9권2호
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• pp.147-149
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• 1999

Biotransformation of exogenous (-)-(4R)-isopiperitenone in cell suspension cultures of Mentha piperita resulted in oxidized products, with (-)-7-hydroxyisopiperitenone being the major compound. The mass of products obtained $unde^{18}O_2$, atmosphere was two units higher than that under normal atmosphere. The biotransformation was inhibited by several cytochrome P450-specific inhibitors as well as by carbon monoxide. Carbon monooxide inhibition was substantially overcome by irradiation of cells with blue light including light at 450nm wavelength. These results suggested that a cytochrome P450-type monooxygenase was involved in the biotransformation.

• Biomolecules & Therapeutics
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• 제27권6호
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• pp.577-583
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• 2019

Human cytochrome P450 2C9 is a highly polymorphic enzyme that is required for drug and xenobiotic metabolism. Here, we studied eleven P450 2C9 genetic variants-including three novel variants F69S, L310V, and Q324X-that were clinically identified in Korean patients. P450 2C9 variant enzymes were expressed in Escherichia coli and their bicistronic membrane fractions were prepared The CO-binding spectra were obtained for nine enzyme variants, indicating P450 holoenzymes, but not for the M02 (L90P) variant. The M11 (Q324X) variant could not be expressed due to an early nonsense mutation. LC-MS/MS analysis was performed to measure the catalytic activities of the P450 2C9 variants, using diclofenac as a substrate. Steady-state kinetic analysis revealed that the catalytic efficiency of all nine P450 2C9 variants was lower than that of the wild type P450 2C9 enzyme. The M05 (R150L) and M06 (P279T) variants showed high $k_{cat}$ values; however, their $K_m$ values were also high. As the M01 (F69S), M03 (R124Q), M04 (R125H), M08 (I359L), M09 (I359T), and M10 (A477T) variants exhibited higher $K_m$ and lower $k_{cat}$ values than that of the wild type enzyme, their catalytic efficiency decreased by approximately 50-fold compared to the wild type enzyme. Furthermore, the novel variant M07 (L310V) showed lower $k_{cat}$ and $K_m$ values than the wild type enzyme, which resulted in its decreased (80%) catalytic efficiency. The X-ray crystal structure of P450 2C9 revealed the presence of mutations in the residues surrounding the substrate-binding cavity. Functional characterization of these genetic variants can help understand the pharmacogenetic outcomes.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.149.3-150
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• 2003

CYP3A4 is the most abundant human CYP and oxidizes a diversity of substrates. including various drugs. steroids. and carcinogens. A variety of metal ions are known to affect microsomal monooxygenase activities. Effects of a series of divalent metal ions on the CYP3A4-catalyzed reaction of reconstituted system containing purified CYP3A4. NADPH-P450 reductase (NPR), and cytochrome b5 (b5) were examined. (omitted)