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The mechanism of the conversion of alpha-eleostearic acid into conjugated linoleic acid

Wu Qiming 東北大学

2020.09.25

概要

Conjugated fatty acids are geometric and positional isomers with several conjugated double bonds. Among conjugated fatty acids, conjugated linoleic acid (CLA; C18:2) is a collective term linoleic acid (cis9,cis12-18:2) with two conjugated double bonds (Fig. 1). More than 28 isoforms of CLA were found due to the various arrangement of positional and geometric variations1). CLA-rich foods are considered as functional foods, because several of them, like cis-9,trans-11 (c9,t11)- and t10,c12-CLA were reported to have various beneficial effects on physiological functions, such as anti-obesity and anticarcinogenic activities, immune enhancement, bone formation improvement, and lipid metabolism regulation in in vivo and in vitro studies1,2). And the main sources of CLA for humans are commonly found in dairy products and ruminant meat. Dairy products are the principal source of CLA in human diets, however, the CLA intake from dietary sources is far from the intended effective dosage due to the low content of CLA in nature3), as the CLA are naturally present in very small amounts in these foodstuffs which typically contain fat in the range from 2.9 to 8.9 mg/g 4). Accordingly, it is necessary to supplement the human diet with CLA supplements to reach the intended effective dosage.

　However, it is important to note that the balance of the different CLA isoforms is heavily distorted in supplements because the CLA in supplements is not derived from natural foods but prepared by chemically altering the linoleic acid found in vegetable oils, which would lead to generate types of CLA isoforms that are never found in large amounts in nature. Specifically, the most of the commercially available CLA supplements contain almost equal amounts of the two major isomers c9,t11-CLA (40.85-41.1 %) and t10,c12-CLA (43.5-44.9%), and significant levels of other CLA isomers (4.6%-10%)5). While the c9,t11-CLA is believed to be the most common natural form of CLA comprising 80 to 90% of the total CLA in food products from ruminants, whereas t10,c12-CLA is present at a level of 3-5%, and other isomers are present in very small amounts 6,7). For these reasons, CLA supplements do not provide the same health effects as CLA from natural foods. What is more, it has been reported that mice fed the highly purified t10, c12-CLA isomer had adverse side effects such as insulin resistance, robust hyperinsulinemia, and massive liver steatosis 8-10). Furthermore, insulin resistance has also been detected in obese men treated with purified t10,c12-CLA11), which raises concerns about the safety of dietary supplements containing the t10,c12-CLA isomer. On the other hand, c9,t11- CLA, which was found to improve the increased insulin resistance caused by t10,c12-CLA9,12), is considered safer due to fewer reported side effects.

　The content of conjugated linolenic acid (CLnA; C18:3) with three conjugated double bonds in seed oil from certain plants can comprise up more than 80% of the total lipid content, which is in contrast to the generally low content of CLA in nature. We are particularly interested in these CLnA-rich seed oils, because CLnA is the only conjugated fatty acid that can be prepared from natural sources in bulk13). For example, α-eleostearic acid (α-ESA; c9,t11,t13-CLnA) comprises up to 60% (wt/wt) of the total lipid content of bitter gourd seed oil and 76% of the total lipid content of tung seed oil, whereas punicic acid (PA; c9,t11,c13-CLnA) comprises up to 74.5% of the total lipid content of pomegranate seed oil, and jacaric acid (JA; c8,t10,c12-CLnA) is found at a concentration of 15.9% in jacaranda seed oil. In addition, α-ESA has been reported to have a new confirmed strong antiangiogenic effect 14-17). We first reported that α- ESA was converted into c9,t11-CLA in 1% α-ESA-fed rats18). Moreover, similar conversions of CLnA into CLA in PA- and JA-fed rats, where PA was converted into c9,t11-CLA and JA was converted into c8,t10-CLA, were also observed in rats13,19). These conversions were also confirmed in mice and humans by other reporters20-22).

　Endogenous CLA synthesis from vaccenic acid (t11-18:1), a major intermediate produced during the ruminal biohydrogenation, is dependent on Δ9-desaturase6,23). And this synthetic pathway has also been found in rodents24,25), pigs26), and other species27). Another pathway for endogenous CLA synthesis is formed as an intermediate during the bio-hydrogenation of linoleic acid to stearic acid (18:0) by B.fibrisolvens and other rumen bacteria28). Although the major source of CLA in humans comes from dietary intake, endogenous synthesis of CLA from vaccenic acid was also been reported in humans29,30) and other non-ruminants25,31,32). Accordingly, the conversion of CLnA into CLA could be a novel pathway for endogenous CLA synthesis. As CLnA can be prepared more easily than CLA, once the mechanism of this conversion is elucidated, it is expected that CLnA, especially α-ESA will be a new source for CLA synthesis or supplant CLA as a dietary supplement.

　Although, we have proved that some specific CLnAs can be converted into their corresponding CLAs, still very little is known of this underlying mechanism (Fig. 2). Our ultimate goal is to elucidate the conversional mechanism of CLnA into CLA by using multidisciplinary approaches. For this purpose, we focused on the conversion of α-ESA into c9,t11-CLA, which is a representative conversion of CLnA into CLA, and we found that this conversion is a NADPH-dependent enzymatic reaction occurring mostly in the rat liver18,33). For further research on this conversion, in this dissertation, firstly we aimed to elucidate conversional mechanism of α-ESA into c9,t11-CLA, especially identify the key enzyme α-ESA saturase responsible for this conversion. Secondly, we aimed to solubilize and purify of α-ESA saturase from liver, and this would enable us to study the properties and characteristics of α- ESA saturase. In addition, this dissertation might provide some inspirations for elucidating the conversion of other CLnA, such as PA and JA, into CLA. And it will also help fill the critical knowledge gap of the mechanism of CLnA convert into CLA.

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1) Benjamin, S.; Prakasan, P.; Sreedharan, S.; Wright, A. D.; Spener, F. Pros and cons of CLA consumption: an insight from clinical evidences. Nutr Metab (Lond) 12, 4 (2015).

2) de Carvalho, E. B. T.; de Melo, I. L. P.; Mancini-Filho, J. Chemical and physiological aspects of isomers of conjugated fatty acids. Ciencia E Tecnologia De Alimentos 30, 295-307 (2010).

3) Kumari, S.; Yong Meng, G.; Ebrahimi, M. Conjugated linoleic acid as functional food in poultry products: A review. Int. J. Food Prop. 20, 491-506 (2016).

4) Eynard, A. R.; Lopez, C. B. Conjugated linoleic acid (CLA) versus saturated fats/cholesterol: their proportion in fatty and lean meats may affect the risk of developing colon cancer. Lipids Health Dis. 2, 6 (2003).

5) Pariza, M. W.; Park, Y.; Cook, M. E. Mechanisms of action of conjugated linoleic acid: evidence and speculation. Proc. Soc. Exp. Biol. Med. 223, 8-13 (2000).

6) Khanal, R. C.; Dhiman, T. R. Biosynthesis of Conjugated Linoleic Acid (CLA): A Review. Pakistan J. Nutr 3, 72-81 (2004).

7) Miranda, J.; Arias, N.; Fernandez-Quintela, A.; del Puy Portillo, M. Are conjugated linolenic acid isomers an alternative to conjugated linoleic acid isomers in obesity prevention? Endocrinol Nutr 61, 209-219 (2014).

8) Clement, L.; Poirier, H.; Niot, I.; Bocher, V.; Guerre-Millo, M.; Krief, S.; Staels, B.; Besnard, P. Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse. J. Lipid Res. 43, 1400-1409 (2002).

9) Park, Y.; Pariza, M. W. Mechanisms of body fat modulation by conjugated linoleic acid (CLA). Food Res. Int. 40, 311-323 (2007).

10) Poirier, H.; Shapiro, J. S.; Kim, R. J.; Lazar, M. A. Nutritional supplementation with trans-10, cis- 12-conjugated linoleic acid induces inflammation of white adipose tissue. Diabetes 55, 1634-1641 (2006).

11) Riserus, U.; Arner, P.; Brismar, K.; Vessby, B. Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care 25, 1516-1521 (2002).

12) Song, H. J.; Sneddon, A. A.; Barker, P. A.; Bestwick, C.; Choe, S. N.; McClinton, S.; Grant, I.; Rotondo, D.; Heys, S. D.; Wahle, K. W. Conjugated linoleic acid inhibits proliferation and modulates protein kinase C isoforms in human prostate cancer cells. Nutr. Cancer 49, 100-108 (2004).

13) Tsuzuki, T.; Kawakami, Y.; Abe, R.; Nakagawa, K.; Koba, K.; Imamura, J.; Iwata, T.; Ikeda, I.; Miyazawa, T. Conjugated linolenic acid is slowly absorbed in rat intestine, but quickly converted to conjugated linoleic acid. J. Nutr. 136, 2153-2159 (2006).

14) Tsuduki, T. Research on food and nutrition characteristics of conjugated fatty acids. Biosci. Biotechnol. Biochem. 79, 1217-1222 (2015).

15) Tsuzuki, T.; Kawakami, Y. Tumor angiogenesis suppression by alpha-eleostearic acid, a linolenic acid isomer with a conjugated triene system, via peroxisome proliferator-activated receptor gamma. Carcinogenesis 29, 797-806 (2008).

16) Shinohara, N.; Tsuduki, T.; Ito, J.; Honma, T.; Kijima, R.; Sugawara, S.; Arai, T.; Yamasaki, M.; Ikezaki, A.; Yokoyama, M.; Nishiyama, K.; Nakagawa, K.; Miyazawa, T.; Ikeda, I. Jacaric acid, a linolenic acid isomer with a conjugated triene system, has a strong antitumor effect in vitro and in vivo. Biochimica Et Biophysica Acta-Molecular And Cell Biology Of Lipids 1821, 980-988 (2012).

17) Tsuzuki, T.; Tokuyama, Y.; Igarashi, M.; Miyazawa, T. Tumor growth suppression by alpha- eleostearic acid, a linolenic acid isomer with a conjugated triene system, via lipid peroxidation. Carcinogenesis 25, 1417-1425 (2004).

18) Tsuzuki, T.; Igarashi, M.; Komai, M.; Miyazawa, T. The metabolic conversion of 9,11,13- eleostearic acid (18 : 3) to 9,11-conjugated linoleic acid (18 : 2) in the rat. J. Nutr. Sci. Vitaminol. 49, 195-200 (2003).

19) Kijima, R.; Honma, T.; Ito, J.; Yamasaki, M.; Ikezaki, A.; Motonaga, C.; Nishiyama, K.; Tsuduki, T. Jacaric Acid is Rapidly Metabolized to Conjugated Linoleic Acid in Rats. J.Oleo. Sci. 62, 305-312 (2013).

20) Yuan, G.-F.; Sinclair, A. J.; Zhou, C.-Q.; Li, D. α-Eleostearic acid is more effectively metabolized into conjugated linoleic acid than punicic acid in mice. J. Sci. Food Agric. 89, 1006-1011 (2009).

21) Yuan, G.; Sinclair, A. J.; Xu, C.; Li, D. Incorporation and metabolism of punicic acid in healthy young humans. Mol. Nutr. Food Res. 53, 1336-1342 (2009).

22) Schneider, A. C.; Mignolet, E.; Schneider, Y. J.; Larondelle, Y. Uptake of conjugated linolenic acids and conversion to cis-9, trans-11-or trans-9, trans-11-conjugated linoleic acids in Caco-2 cells. Br. J. Nutr. 109, 57-64 (2013).

23) Griinari, J. M.; Corl, B. A.; Lacy, S. H.; Chouinard, P. Y.; Nurmela, K. V. V.; Bauman, D. E. Conjugated linoleic acid is synthesized endogenously in lactating dairy cows by Delta(9)-desaturase. J. Nutr. 130, 2285-2291 (2000).

24) Banni, S.; Angioni, E.; Murru, E.; Carta, G.; Melis, M. P.; Bauman, D.; Dong, Y.; Ip, C. Vaccenic acid feeding increases tissue levels of conjugated linoleic acid and suppresses development of premalignant lesions in rat mammary gland. Nutr. Cancer 41, 91-97 (2001).

25) Corl, B. A.; Barbano, D. M.; Bauman, D. E.; Ip, C. cis-9, trans-11 CLA derived endogenously from trans-11 18 : 1 reduces cancer risk in rats. J. Nutr. 133, 2893-2900 (2003).

26) Glaser, K. R.; Wenk, C.; Scheeder, M. R. L. Effects of feeding pigs increasing levels of C 18 : 1 trans fatty acids on fatty acid composition of backfat and intramuscular fat as well as backfat firmness. Arch Anim Nutr 56, 117-130 (2002).

27) Palmquist, D. L.; Lock, A. L.; Shingfield, K. J.; Bauman, D. E. Biosynthesis of conjugated linoleic acid in ruminants and humans. Adv. Food Nutr. Res. 50, 179-217 (2005).

28) Lourenco, M.; Ramos-Morales, E.; Wallace, R. J. The role of microbes in rumen lipolysis and biohydrogenation and their manipulation. Animal 4, 1008-1023 (2010).

29) Adlof, R. O.; Duval, S.; Emken, E. A. Biosynthesis of conjugated linoleic acid in humans. Lipids 35, 131-135 (2000).

30) Attar-Bashi, N. M.; Weisinger, R. S.; Begg, D. P.; Li, D.; Sinclair, A. J. Failure of conjugated linoleic acid supplementation to enhance biosynthesis of docosahexaenoic acid from alpha-linolenic acid in healthy human volunteers. Prostag. Leuko. Ess.s 76, 121-130 (2007).

31) Turpeinen, A. M.; Mutanen, M.; Aro, A.; Salminen, I.; Basu, S.; Palmquist, D. L.; Griinari, J. M. Bioconversion of vaccenic acid to conjugated linoleic acid in humans. Am. J. Clin. Nutr. 76, 504-510 (2002).

32) Santora, J. E.; Palmquist, D. L.; Roehrig, K. L. Trans-vaccenic acid is desaturated to conjugated linoleic acid in mice. J. Nutr. 130, 208-215 (2000).

33) Tsuzuki, T.; Tokuyama, Y.; Igarashi, M.; Nakagawa, K.; Ohsaki, Y.; Komai, M.; Miyazawa, T. alpha-Eleostearic acid (9Z11E13E-18 : 3) is quickly converted to conjugated linoleic acid (9Z11E-18 : 2) in rats. J. Nutr. 134, 2634-2639 (2004).

34) Bligh, E. G.; Dyer, W. J. A Rapid Method Of Total Lipid Extraction And Purification. Can. J. Biochem. Physiol. 37, 911-917 (1959).

35) Igarashi, M.; Tsuzuki, T.; Kambe, T.; Miyazawa, T. Recommended methods of fatty acid methylester preparation for conjugated dienes and trienes in food and biological samples. J. Nutr. Sci. Vitaminol. (Tokyo) 50, 121-128 (2004).

36) Nagy, K.; Tiuca, I.-D.: Importance of fatty acids in physiopathology of human body. In Fatty acids; IntechOpen, 2017.

37) Fisk, H. L.; West, A. L.; Childs, C. E.; Burdge, G. C.; Calder, P. C. The Use of Gas Chromatography to Analyze Compositional Changes of Fatty Acids in Rat Liver Tissue during Pregnancy. Jove-J. Vis. Exp.85:e5144 (2014).

38) Iwagaki, Y.; Sugawara, S.; Huruya, Y.; Sato, M.; Wu, Q. M.; E, S.; Yamamoto, K.; Tsuduki, T. The 1975 Japanese diet has a stress reduction effect in mice: search for physiological effects using metabolome analysis. Biosci., Biotechnol., Biochem. 82, 709-715 (2018).

39) Xiao, W. S.; Wang, R. S.; Handy, D. E.; Loscalzo, J. NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism. Antioxid Redox Sign 28, 251-272 (2018).

40) Ying, W. H. NAD(+)/ NADH and NADP(+)/NADPH in cellular functions and cell death: Regulation and biological consequences. Antioxid Redox Sign 10, 179-206 (2008).

41) Heinemann, F. S.; Ozols, J. Isolation and structural analysis of microsomal membrane proteins. Front. Biosci. 3, d483-493 (1998).

42) Neve, E. P. A.; Ingelman-Sundberg, M. Cytochrome P450 proteins: Retention and distribution from the endoplasmic reticulum. Curr Opin Drug Disc 13, 78-85 (2010).

43) Jarrar, Y. B.; Lee, S. J. Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications. Int J Mol Sci 20 (2019).

44) Miyamoto, M.; Yamashita, T.; Yasuhara, Y.; Hayasaki, A.; Hosokawa, Y.; Tsujino, H.; Uno, T. Membrane anchor of cytochrome P450 reductase suppresses the uncoupling of cytochrome P450. Chem. Pharm. Bull. (Tokyo) 63, 286-294 (2015).

45) Powell, W. S.; Gravelle, F. Conversion Of Stereoisomers Of Leukotriene-B4 To Dihydro And Tetrahydro Metabolites by Porcine Leukocytes. Biochim. Biophys. Acta 1044, 147-157 (1990).

46) Hori, T.; Yokomizo, T.; Ago, H.; Sugahara, M.; Ueno, G.; Yamamoto, M.; Kumasaka, T.; Shimizu, T.; Miyano, M. Structural basis of leukotriene B4 12-hydroxydehydrogenase/15-Oxo-prostaglandin 13- reductase catalytic mechanism and a possible Src homology 3 domain binding loop. J. Biol. Chem. 279, 22615-22623 (2004).

47) Clish, C. B.; Sun, Y. P.; Serhan, C. N. Identification of dual cyclooxygenase-eicosanoid oxidoreductase inhibitors: NSAIDs that inhibit PG-LX reductase/LTB(4) dehydrogenase. Biochem. Biophys. Res. Commun. 288, 868-874 (2001).

48) Clish, C. B.; Levy, B. D.; Chiang, N.; Tai, H. H.; Serhan, C. N. Oxidoreductases in lipoxin A4 metabolic inactivation: a novel role for 15-onoprostaglandin 13-reductase/leukotriene B4 12- hydroxydehydrogenase in inflammation. J. Biol. Chem. 275, 25372-25380 (2000).

49) Sakanoi, Y.; E, S.; Yamamoto, K.; Ota, T.; Seki, K.; Imai, M.; Ota, R.; Asayama, Y.; Nakashima, A.; Suzuki, K.; Tsuduki, T. Simultaneous Intake of Euglena Gracilis and Vegetables Synergistically Exerts an Anti-Inflammatory Effect and Attenuates Visceral Fat Accumulation by Affecting Gut Microbiota in Mice. Nutrients 10 (2018).

50) Wu, Q.; E, S.; Yamamoto, K.; Tsuduki, T. Carbohydrate-restricted diet promotes skin senescence in senescence-accelerated prone mice. Biogerontology 20, 71-82 (2019).

51) Akoglu, H. User's guide to correlation coefficients. Turk J Emerg Med 18, 91-93 (2018).

52) Henderson, C. J.; McLaughlin, L. A.; Wolf, C. R. Evidence that cytochrome b5 and cytochrome b5 reductase can act as sole electron donors to the hepatic cytochrome P450 system. Mol. Pharmacol. 83, 1209-1217 (2013).

53) Gan, L.; von Moltke, L. L.; Trepanier, L. A.; Harmatz, J. S.; Greenblatt, D. J.; Court, M. H. Role of NADPH-cytochrome P450 reductase and cytochrome-b5/NADH-b5 reductase in variability of CYP3A activity in human liver microsomes. Drug Metab. Dispos. 37, 90-96 (2009).

54) Suski, J. M.; Lebiedzinska, M.; Wojtala, A.; Duszynski, J.; Giorgi, C.; Pinton, P.; Wieckowski, M. R. Isolation of plasma membrane-associated membranes from rat liver. Nat. Protoc. 9, 312-322 (2014).

55) LaMontagne, E. D.; Collins, C. A.; Peck, S. C.; Heese, A. Isolation of Microsomal Membrane Proteins from Arabidopsis thaliana. Curr. Protoc. Plant Biol. 1, 217-234 (2016).

56) Williamson, C. D.; Wong, D. S.; Bozidis, P.; Zhang, A.; Colberg-Poley, A. M. Isolation of Endoplasmic Reticulum, Mitochondria, and Mitochondria-Associated Membrane and Detergent Resistant Membrane Fractions from Transfected Cells and from Human Cytomegalovirus-Infected Primary Fibroblasts. Curr. Protoc. Cell Biol. 68, 3 27 21-23 27 33 (2015).

57) Wienkers, L. C.; Heath, T. G. Predicting in vivo drug interactions from in vitro drug discovery data. Nat. Rev. Drug Discov. 4, 825-833 (2005).

58) Peng, F.; Zhan, X.; Li, M. Y.; Fang, F.; Li, G.; Li, C.; Zhang, P. F.; Chen, Z. Proteomic and bioinformatics analyses of mouse liver microsomes. International journal of proteomics 2012, 832569 (2012).

59) Fisher, M. B.; Campanale, K.; Ackermann, B. L.; Vandenbranden, M.; Wrighton, S. A. In vitro glucuronidation using human liver microsomes and the pore-forming peptide alamethicin. Drug Metab. Disposition 28, 560-566 (2000).

60) Murakami, K.; Mihara, K.; Omura, T. The Transmembrane Region Of Microsomal Cytochrome- P450 Identified as the Endoplasmic-Reticulum Retention Signal. J. Biochem. 116, 164-175 (1994).

61) Lamb, D. C.; Waterman, M. R. Unusual properties of the cytochrome P450 superfamily. Philos. Trans. R. Soc. Lond. B Biol. Sci. 368, 20120434 (2013).

62) Dörr, J. Membrane solubilization by styrene –maleic acid copolymers: towards new applications in membrane protein research. Utrecht University, 2017.

63) Ryan, D. E.; Levin, W. Purification and characterization of hepatic microsomal cytochrome P- 450. Pharmacol. Ther. 45, 153-239 (1990).

64) Ryan, D. E.; Iida, S.; Wood, A. W.; Thomas, P. E.; Lieber, C. S.; Levin, W. Characterization of three highly purified cytochromes P-450 from hepatic microsomes of adult male rats. J. Biol. Chem. 259, 1239-1250 (1984).

65) Sasaki, M.; Akahira, A.; Oshiman, K.; Tsuchido, T.; Matsumura, Y. Purification of cytochrome P450 and ferredoxin, involved in bisphenol A degradation, from Sphingomonas sp. strain AO1. Appl. Environ. Microbiol. 71, 8024-8030 (2005).

66) Kramer, J. K.; Fellner, V.; Dugan, M. E.; Sauer, F. D.; Mossoba, M. M.; Yurawecz, M. P. Evaluating acid and base catalysts in the methylation of milk and rumen fatty acids with special emphasis on conjugated dienes and total trans fatty acids. Lipids 32, 1219-1228 (1997).

67) Knights, K. M.; Stresser, D. M.; Miners, J. O.; Crespi, C. L. In Vitro Drug Metabolism Using Liver Microsomes. Curr. Protoc. Pharmacol. 74, 7 8 1-7 8 24 (2016).

68) Turpeinen, M.; Korhonen, L. E.; Tolonen, A.; Uusitalo, J.; Juvonen, R.; Raunio, H.; Pelkonen, O. Cytochrome P450 (CYP) inhibition screening: Comparison of three tests. Eur. J. Pharm. Sci. 29, 130- 138 (2006).

69) Parkinson, A.; Kazmi, F.; Buckley, D. B.; Yerino, P.; Paris, B. L.; Holsapple, J.; Toren, P.; Otradovec, S. M.; Ogilvie, B. W. An evaluation of the dilution method for identifying metabolism-dependent inhibitors of cytochrome P450 enzymes. Drug Metab. Dispos. 39, 1370-1387 (2011).

70) Cederbaum, A. I. Molecular mechanisms of the microsomal mixed function oxidases and biological and pathological implications. Redox Biol 4, 60-73 (2015).

71) Chen, Z. H.; Zhang, S. X.; Long, N.; Lin, L. S.; Chen, T.; Zhang, F. P.; Lv, X. Q.; Ye, P. Z.; Li, N.; Zhang, K. Z. An improved substrate cocktail for assessing direct inhibition and time-dependent inhibition of multiple cytochrome P450s. Acta Pharmacol. Sin. 37, 708-718 (2016).

72) Guengerich, F. P. Cytochrome p450 and chemical toxicology. Chem. Res. Toxicol. 21, 70-83 (2008).

73) Zanger, U. M.; Schwab, M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol. Ther. 138, 103-141 (2013).

74) Edson, K. Z.; Rettie, A. E. CYP4 enzymes as potential drug targets: focus on enzyme multiplicity, inducers and inhibitors, and therapeutic modulation of 20-hydroxyeicosatetraenoic acid (20-HETE) synthase and fatty acid omega-hydroxylase activities. Curr. Top. Med. Chem. 13, 1429-1440 (2013).

75) Pelkonen, O.; Myllynen, P.; Taavitsainen, P.; Boobis, A. R.; Watts, P.; Lake, B. G.; Price, R. J.; Renwick, A. B.; Gomez-Lechon, M. J.; Castell, J. V.; Ingelman-Sundberg, M.; Hidestrand, M.; Guillouzo, A.; Corcos, L.; Goldfarb, P. S.; Lewis, D. F. Carbamazepine: a 'blind' assessment of CVP- associated metabolism and interactions in human liver-derived in vitro systems. Xenobiotica 31, 321- 343 (2001).

76) Wang, M. Z.; Saulter, J. Y.; Usuki, E.; Cheung, Y. L.; Hall, M.; Bridges, A. S.; Loewen, G.; Parkinson, O. T.; Stephens, C. E.; Allen, J. L.; Zeldin, D. C.; Boykin, D. W.; Tidwell, R. R.; Parkinson, A.; Paine, M. F.; Hall, J. E. CYP4F enzymes are the major enzymes in human liver microsomes that catalyze the O-demethylation of the antiparasitic prodrug DB289 [2,5-bis(4-amidinophenyl)furan-bis- O-methylamidoxime]. Drug Metab. Dispos. 34, 1985-1994 (2006).

77) Gray, J. P.; Mishin, V.; Heck, D. E.; Laskin, D. L.; Laskin, J. D. Inhibition of NADPH cytochrome P450 reductase by the model sulfur mustard vesicant 2-chloroethyl ethyl sulfide is associated with increased production of reactive oxygen species. Toxicol. Appl. Pharmacol. 247, 76-82 (2010).

78) Itoh, K.; Yamamoto, K.; Adachi, M.; Kosaka, T.; Tanaka, Y. Leukotriene B4 12- hydroxydehydrogenase/15-ketoprostaglandin Delta 13-reductase (LTB4 12-HD/PGR) responsible for the reduction of a double-bond of the alpha,beta-unsaturated ketone of an aryl propionic acid non- steroidal anti-inflammatory agent CS-670. Xenobiotica 38, 249-263 (2008).

79) Baer, B. R.; Rettie, A. E. CYP4B1: an enigmatic P450 at the interface between xenobiotic and endobiotic metabolism. Drug Metab. Rev. 38, 451-476 (2006).

80) Sanders, R. J.; Ofman, R.; Duran, M.; Kemp, S.; Wanders, R. J. Omega-oxidation of very long- chain fatty acids in human liver microsomes. Implications for X-linked adrenoleukodystrophy. J. Biol. Chem. 281, 13180-13187 (2006).

81) Urlacher, V. B.; Girhard, M. Cytochrome P450 Monooxygenases in Biotechnology and Synthetic Biology. Trends Biotechnol. 37, 882-897 (2019).

82) Amunom, I.; Srivastava, S.; Prough, R. A. Aldehyde reduction by cytochrome P450. Curr. Protoc. Toxicol. Chapter 4, Unit4 37 (2011).

83) Amunom, I.; Dieter, L. J.; Tamasi, V.; Cai, J.; Conklin, D. J.; Srivastava, S.; Martin, M. V.; Guengerich, F. P.; Prough, R. A. Cytochromes P450 catalyze the reduction of alpha,beta-unsaturated aldehydes. Chem. Res. Toxicol. 24, 1223-1230 (2011).

84) Fu, Z. D.; Selwyn, F. P.; Cui, J. Y.; Klaassen, C. D. RNA Sequencing Quantification of Xenobiotic-Processing Genes in Various Sections of the Intestine in Comparison to the Liver of Male Mice. Drug Metab. Dispos. 44, 842-856 (2016).

85) Kalsotra, A.; Strobel, H. W. Cytochrome P450 4F subfamily: at the crossroads of eicosanoid and drug metabolism. Pharmacol. Ther. 112, 589-611 (2006).

86) Qiu, W. H.; Fu, Z.; Xu, G. Y. G.; Grassucci, R. A.; Zhang, Y.; Frank, J.; Hendrickson, W. A.; Guo, Y. Z. Structure and activity of lipid bilayer within a membrane-protein transporter. Proc. Natl. Acad. Sci. U. S. A. 115, 12985-12990 (2018).

87) Pamplona, R. Membrane phospholipids, lipoxidative damage and molecular integrity: A causal role in aging and longevity. BBA-Bioenergetics 1777, 1249-1262 (2008).

88) Heerklotz, H. Triton promotes domain formation in lipid raft mixtures. Biophys. J. 83, 2693-2701 (2002).

89) Lichtenberg, D.; Goni, F. M.; Heerklotz, H. Detergent-resistant membranes should not be identified with membrane rafts. Trends Biochem. Sci. 30, 430-436 (2005).

90) Lichtenberg, D.; Ahyayauch, H.; Goni, F. M. The Mechanism of Detergent Solubilization of Lipid Bilayers. Biophys. J. 105, 289-299 (2013).

91) Casares, D.; Escriba, P. V.; Rossello, C. A. Membrane Lipid Composition: Effect on Membrane and Organelle Structure, Function and Compartmentalization and Therapeutic Avenues. Int. J. Mol .Sci. 20 (2019).

92) Ingelmansundberg, M.; Blanck, J.; Smettan, G.; Ruckpaul, K. Reduction Of Cytochrome-P-450 Lm2 by Nadph In Reconstituted Phospholipid-Vesicles Is Dependent on Membrane Charge. Eur. J. Biochem. 134, 157-162 (1983).

93) Ingelmansundberg, M.; Ekstrom, G.; Tindberg, N.; Johansson, I. Lipid-Peroxidation Dependent on Ethanol-Inducible Cytochrome P450 From Rat Liver. Adv.Biophys. 22,43-47 (1987).

94) Ingelmansundberg, M.; Gustafsson, J. A. Role Of Phospholipids In Cytochrome P-450-Catalyzed Reactions. Biochem. Soc. Trans. 3, 977-977 (1975).

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