Substrate Specificity of the Cytochrome P450 Enzymes CYP79A1 and CYP71E1 Involved in the Biosynthesis of the Cyanogenic Glucoside Dhurrin inSorghum bicolor(L.) Moench

1999 ◽  
Vol 363 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Rachel Alice Kahn ◽  
Theodor Fahrendorf ◽  
Barbara Ann Halkier ◽  
Birger Lindberg Møller
Keyword(s):  
Cytochrome P450 ◽  
Substrate Specificity ◽  
Cytochrome P450 Enzymes ◽  
Cyanogenic Glucoside

Directed evolution of cytochrome P450 enzymes for biocatalysis: exploiting the catalytic versatility of enzymes with relaxed substrate specificity

2015 ◽  
Vol 467 (1) ◽  
pp. 1-15 ◽  
Author(s):  
James B.Y.H. Behrendorff ◽  
Weiliang Huang ◽  
Elizabeth M.J. Gillam
Keyword(s):  
Cytochrome P450 ◽  
Substrate Specificity ◽  
Directed Evolution ◽  
Practical Application ◽  
Cytochrome P450 Enzymes ◽  
Level Of Activity ◽  
Modern Chemical ◽  
Stereo Selectivity ◽  
High Degree ◽  
Made In

Cytochrome P450 enzymes are renowned for their ability to insert oxygen into an enormous variety of compounds with a high degree of chemo- and regio-selectivity under mild conditions. This property has been exploited in Nature for an enormous variety of physiological functions, and representatives of this ancient enzyme family have been identified in all kingdoms of life. The catalytic versatility of P450s makes them well suited for repurposing for the synthesis of fine chemicals such as drugs. Although these enzymes have not evolved in Nature to perform the reactions required for modern chemical industries, many P450s show relaxed substrate specificity and exhibit some degree of activity towards non-natural substrates of relevance to applications such as drug development. Directed evolution and other protein engineering methods can be used to improve upon this low level of activity and convert these promiscuous generalist enzymes into specialists capable of mediating reactions of interest with exquisite regio- and stereo-selectivity. Although there are some notable successes in exploiting P450s from natural sources in metabolic engineering, and P450s have been proven repeatedly to be excellent material for engineering, there are few examples to date of practical application of engineered P450s. The purpose of the present review is to illustrate the progress that has been made in altering properties of P450s such as substrate range, cofactor preference and stability, and outline some of the remaining challenges that must be overcome for industrial application of these powerful biocatalysts.

Pharmacogenomics of Cytochrome P450 Enzymes in Tumours

2004 ◽  
Vol 2 (3) ◽  
pp. 243-254 ◽  
Author(s):  
Diane Downie ◽  
Patrick Rooney ◽  
Morag McFadyen ◽  
Graeme Murray
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzymes

Engineering Cytochrome P450 Enzymes

2008 ◽  
Vol 21 (1) ◽  
pp. 220-231 ◽  
Author(s):  
Elizabeth M. J. Gillam
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzymes

scholarly journals Exploring the effect of khat (Catha edulis) chewing on the pharmacokinetics of the antiplatelet drug clopidogrel in rats using the newly developed LC-MS/MS technique

2020 ◽  
Vol 18 (1) ◽  
pp. 681-690
Author(s):  
Hassan A. Alhazmi ◽  
Adnan A. Kadi ◽  
Mohamed W. Attwa ◽  
Waquar Ahsan ◽  
Manal Mohamed Elhassan Taha ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Active Metabolite ◽  
Dose Adjustment ◽  
Internal Standard ◽  
Cardiovascular Complications ◽  
Antiplatelet Drug ◽  
Peak Ratio ◽  
Cytochrome P450 Enzymes ◽  
Time Intervals ◽  
Addictive Substance

AbstractClopidogrel (CLOP) is widely used worldwide for cardiovascular complications. CLOP is highly metabolized in the liver to its active metabolite by cytochrome P450 enzymes. Studies have shown that khat, an addictive substance, is a powerful inhibitor of cytochrome P450 enzymes and can influence the metabolism of drugs that are concomitantly used. Therefore, this study was designed to evaluate the effects of khat on the pharmacokinetics of CLOP in rats. In this study, rats were administered either CLOP alone or CLOP combined with khat and their plasma were obtained at different time intervals and analyzed using the newly developed and validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method using foretinib (FTB) as the internal standard. The corresponding peak area of the analyte versus FTB was used for calculating the peak ratio. The validated LC-MS/MS method resulted in the separation of the well-defined quantifiable peaks of CLOP, FTB, and CLOP metabolite within 7 min. Results showed a significant influence of khat on the peak ratio of CLOP metabolite, which was found to be significantly decreased (P < 0.05) in comparison to CLOP alone, suggesting significant decrease in the conversion of CLOP to its active metabolite due to the inhibition of CYP450 enzymes by khat. Therefore, there might be a need for dose adjustment for regular khat chewers using CLOP.

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