| Name | cytochrome P450 (protein family or complex) |
|---|---|
| Synonyms | cytochrome P450; cytochrome P 450; CYP450; CYP 450 |
| Name | acrolein |
|---|---|
| CAS | 2-propenal |
| PubMed | Abstract | RScore(About this table) | |
|---|---|---|---|
| 10026857 | Karle P, Muller P, Renz R, Jesnowski R, Saller R, von Rombs K, Nizze H, Liebe S, Gunzburg WH, Salmons B, Lohr M: Intratumoral injection of encapsulated cells producing an oxazaphosphorine activating cytochrome P450 for targeted chemotherapy. Adv Exp Med Biol. 1998;451:97-106. This CYP2B1 gene converts oxazaphosphorines (ifosfamide or cyclophosphamide) to their active cytotoxic compounds, phosphoramide mustard, which alkylates DNA, and acrolein, which alkylates proteins. |
2(0,0,0,2) | Details |
| 10938378 | Nair RB, Joy RW 4th, Kurylo E, Shi X, Schnaider J, Datla RS, Keller WA, Selvaraj G: Identification of a CYP84 family of cytochrome P450-dependent mono-oxygenase genes in Brassica napus and perturbation of their expression for engineering sinapine reduction in the seeds. Plant Physiol. 2000 Aug;123(4):1623-34. |
2(0,0,0,2) | Details |
| 8097772 | Fry JR, Fentem JH, Salim A, Tang SP, Garle MJ, Whiting DA: Structural requirements for the direct and cytochrome P450-dependent reaction of cyclic alpha,beta-unsaturated carbonyl compounds with a study with and related compounds. J Pharm Pharmacol. 1993 Mar;45(3):166-70. Acrolein was used as a positive control for the direct reaction, and produced complete or nearly complete depletion of GSH under all assay conditions. 5,6-Dihydro-2H-pyran-2-one and 2-cyclohexen-1-one also produced substantial depletion of GSH in the direct reaction, which was not increased by the addition of liver microsomes. |
2(0,0,0,2) | Details |
| 10415878 | Muller P, Jesnowski R, Karle P, Renz R, Saller R, Stein H, Puschel K, von Rombs K, Nizze H, Liebe S, Wagner T, Gunzburg WH, Salmons B, Lohr M: Injection of encapsulated cells producing an ifosfamide-activating cytochrome P450 for targeted chemotherapy to pancreatic tumors. Ann N Y Acad Sci. 1999 Jun 30;880:337-51. This CYP2B1 gene converts ifosfamide to its active cytotoxic compounds, phosphoramide mustard, which alkylates DNA, and acrolein, which alkylates proteins. |
2(0,0,0,2) | Details |
| 11525657 | Shaffer CL, Morton MD, Hanzlik RP: N-dealkylation of an N-cyclopropylamine by horseradish peroxidase. J Am Chem Soc. 2001 Sep 5;123(35):8502-8. Neither beta-hydroxypropionaldehyde, acrolein, nor cyclopropanone hydrate are formed as SET metabolites of 3. Cyclopropylamines inactivate cytochrome P450 enzymes which catalyze their oxidative N-dealkylation. |
2(0,0,0,2) | Details |
| 2859667 | Mirkes PE: Cyclophosphamide teratogenesis: a review. Teratog Carcinog Mutagen. 1985;5(2):75-88. Activation of CP to its teratogenic, mutagenic, and antineoplastic form is mediated by microsomal cytochrome P-450 monooxygenases, which convert CP to 4-hydroxycyclophosphamide (4OHCP). In the absence of detoxification, 4OHCP spontaneously breaks down to phosphoramide mustard (PM) and acrolein (AC). |
1(0,0,0,1) | Details |
| 6380709 | Marinello AJ, Bansal SK, Paul B, Koser PL, Love J, Struck RF, Gurtoo HL: Metabolism and binding of cyclophosphamide and its metabolite acrolein to rat hepatic microsomal cytochrome P-450. Cancer Res. 1984 Oct;44(10):4615-21. The results confirmed covalent association between [14C] acrolein and cytochrome P-450 in the microsomes and also demonstrated further metabolism of [14C] acrolein, apparently to an epoxide, which is capable of binding covalently to proteins. |
117(1,2,2,7) | Details |
| 6148213 | Patel JM, Ortiz E, Kolmstetter C, Leibman KC: Selective inactivation of rat lung and liver microsomal -cytochrome c reductase by acrolein. Drug Metab Dispos. 1984 Jul-Aug;12(4):460-3. Addition of acrolein to rat lung or liver microsomal suspensions resulted in total inactivation of -cytochrome c reductase and partial conversion of cytochrome P-450 to P-420 in a concentration- and time-dependent fashion. |
112(1,2,2,2) | Details |
| 7513061 | Barros AR, Sierra LM, Comendador MA: Acrolein genotoxicity in Drosophila melanogaster. Mutat Res. 1994 May;321(3):119-26. In order to investigate the role of metabolism in acrolein genotoxicity in D. melanogaster, the action of several metabolism modifiers, namely phenobarbital, an inducer of xenobiotic metabolism, phenylimidazole and iproniazid, inhibitors of oxidative activities of cytochrome P450, and diethyl a -depleting agent, have been assayed using the sex-linked recessive lethal (SLRL) test, with two different administration routes (feeding and injection). |
81(1,1,1,1) | Details |
| 8495410 | Chang TK, Waxman DJ: Cyclophosphamide modulates rat hepatic cytochrome P450 2C11 and steroid 5 alpha-reductase activity and messenger RNA levels through the combined action of acrolein and phosphoramide mustard. Cancer Res. 1993 Jun 1;53(11):2490-7. |
63(0,2,2,3) | Details |
| 1334014 | Cooper KO, Witz G, Witmer C: The effects of alpha, beta-unsaturated aldehydes on hepatic thiols and thiol-containing enzymes. Fundam Appl Toxicol. 1992 Oct;19(3):343-9. Only at 24 hr, acrolein, muconaldehyde, or crotonaldehyde decreased cytochrome P450 to 61, 71, and 67% of control values, respectively; ethylmorphine N-demethylation was decreased to a greater extent, i.e., to 35, 60, and 23% of controls. |
39(0,1,2,4) | Details |
| 11723234 | Schwartz PS, Waxman DJ: Cyclophosphamide induces caspase 9-dependent apoptosis in 9L tumor cells. . Mol Pharmacol. 2001 Dec;60(6):1268-79. Cyclophosphamide (CPA), a widely used oxazaphosphorine anti-cancer prodrug, is inactive until it is metabolized by cytochrome P450 to yield phosphoramide mustard and acrolein, which alkylate DNA and proteins, respectively. |
33(0,1,1,3) | Details |
| 19103281 | Park D, Jeon JH, Shin S, Joo SS, Kang DH, Moon SH, Jang MJ, Cho YM, Kim JW, Ji HJ, Ahn B, Oh KW, Kim YB: Green tea extract increases cyclophosphamide-induced teratogenesis by modulating the expression of cytochrome P-450 mRNA. Reprod Toxicol. 2009 Jan;27(1):79-84. Epub 2008 Dec 3. Moreover, repeated treatment with GTE greatly increased mRNA expression and activity of hepatic cytochrome P-450 (CYP) 2B, which metabolizes cyclophosphamide into teratogenic acrolein and cytotoxic phosphoramide mustard, while reducing CYP3A expression (a detoxifying enzyme). |
32(0,1,1,2) | Details |
| 15746054 | Braybrooke JP, Slade A, Deplanque G, Harrop R, Madhusudan S, Forster MD, Gibson R, Makris A, Talbot DC, Steiner J, White L, Kan O, Naylor S, Carroll MW, Kingsman SM, Harris AL: Phase I study of MetXia-P450 gene therapy and oral cyclophosphamide for patients with advanced breast cancer or melanoma. Clin Cancer Res. 2005 Feb 15;11(4):1512-20. Cytochrome P450 enzymes are primarily expressed in the liver and convert the prodrug cyclophosphamide to an active phosphoramide mustard and acrolein. |
32(0,1,1,2) | Details |
| 3103627 | Cooper KO, Witmer CM, Witz G: Inhibition of microsomal cytochrome c reductase activity by a series of alpha, beta-unsaturated aldehydes. Biochem Pharmacol. 1987 Mar 1;36(5):627-31. Our laboratory has shown that trans,trans-muconaldehyde (a possible metabolite of as well as acrolein and crotonaldehyde, when added to hepatic microsomes, decreased cytochrome P-450 (measured spectrophotometrically). |
32(0,1,1,2) | Details |
| 10452807 | Huang Z, Waxman DJ: High-performance liquid chromatographic-fluorescent method to determine chloroacetaldehyde, a metabolite of the anticancer drug ifosfamide, in plasma and in liver microsomal incubations. Anal Biochem. 1999 Aug 15;273(1):117-25. By coupling this method with a recently described HPLC-fluorescent method to determine acrolein, a cytochrome P450 metabolite of IFA formed during the activation of the drug by 4-hydroxylation, the two major, alternative P450-catalyzed pathways of IFA metabolism can be monitored from the same plasma samples or liver microsomal incubations and the partitioning of drug between these two pathways thereby quantitated. |
32(0,1,1,2) | Details |
| 18414588 | Klein R, Ruttkowski B, Schwab S, Peterbauer T, Salmons B, Gunzburg WH, Hohenadl C: Mouse mammary tumor virus promoter-containing retroviral promoter conversion vectors for gene-directed enzyme prodrug therapy are functional in vitro and in vivo. J Biomed Biotechnol. 2008;2008:683505. Cytochrome P450 2B1 (CYP2B1) metabolizes the prodrugs cyclophosphamide (CPA) and ifosfamide (IFA) to produce the cytotoxic substances phosphoramide mustard and isophosphoramide mustard as well as the byproduct acrolein. |
31(0,1,1,1) | Details |
| 6541256 | Nagasawa HT, Elberling JA, DeMaster EG: Latent inhibitors of aldehyde dehydrogenase as deterrent agents. J Med Chem. 1984 Oct;27(10):1335-9. The rationale for their preparation was based on the expectation that, like pargyline, which gives rise to propiolaldehyde, oxidative metabolism of the above compounds by the hepatic cytochrome P-450 enzymes would lead to the generation in vivo of the aldehyde dehydrogenase (AlDH) inhibitors, cyclopropanone, acrolein, or chloral. |
31(0,1,1,1) | Details |
| 4026579 | Ohno Y, Ormstad K: Formation, toxicity and inactivation of acrolein during biotransformation of cyclophosphamide as studied in freshly isolated cells from rat liver and kidney. Arch Toxicol. 1985 Jun;57(2):99-103. The results may be summarized as follows: Cyclophosphamide (CTX)-mediated toxicity to isolated cells is dependent on cytochrome P-450 activity; Loss of viability in cells incubated with cyclophosphamide is preceded by a depletion of cellular Stimulation of cellular synthesis or the presence of low molecular weight thiols in the incubation medium protects against cyclophosphamide-induced toxicity; Acrolein is probably formed extracellularly as well as intracellularly and can be detoxified by thiol compounds, forming a thiochemiacetal or a thioether. |
31(0,1,1,1) | Details |
| 16543915 | Gunther M, Waxman DJ, Wagner E, Ogris M: Effects of hypoxia and limited diffusion in tumor cell microenvironment on bystander effect of P450 prodrug therapy. Cancer Gene Ther. 2006 Aug;13(8):771-9. Epub 2006 Mar 17. Cytochrome P450 (CYP) enzyme 2B1 metabolizes the anticancer prodrug cyclophosphamide (CPA) to 4--CPA, which decomposes to the cytotoxic metabolites acrolein and phosphoramide mustard. |
31(0,1,1,1) | Details |
| 3924052 | Weli AM, Lindeke B: The metabolic fate of pargyline in rat liver microsomes. . Biochem Pharmacol. 1985 Jun 1;34(11):1993-8. As propiolaldehyde, a potential hepatotoxin, is formed concomitant to BMA, and as PNO, under certain conditions, can decompose to acrolein, another well-known hepatotoxin, both these quantitatively important metabolic routes have to be considered in evaluating the toxicity of pargyline. Moreover, the inhibition of PNO formation by typical cytochrome P-450 inhibitors is marginal, while that of BPA, BMA and MPA formation is not. |
2(0,0,0,2) | Details |
| 8071856 | Murray M, Butler AM, Stupans I: Competitive inhibition of human liver microsomal cytochrome P450 3A-dependent steroid 6 beta-hydroxylation activity by cyclophosphamide and ifosfamide in vitro. J Pharmacol Exp Ther. 1994 Aug;270(2):645-9. Acrolein (prop-2-enal) is also formed during CP and IF activation in rat liver and has been associated with P450 destruction. |
2(0,0,0,2) | Details |
| 9815909 | Wei MX, Tamiya T, Rhee RJ, Breakefield XO, Chiocca EA: Diffusible cytotoxic metabolites contribute to the in vitro bystander effect associated with the cyclophosphamide/cytochrome P450 2B1 cancer gene therapy paradigm. Clin Cancer Res. 1995 Oct;1(10):1171-7. This enzyme activates CPA into 4-hydroxycyclophosphamide, which ultimately degrades into acrolein and phosphoramide mustard, the anticancer and DNA-alkylating metabolite. |
2(0,0,0,2) | Details |
| 3420943 | Benford DJ, Reavy HJ, Hubbard SA: Metabolizing systems in cell culture cytotoxicity tests. Xenobiotica. 1988 Jun;18(6):649-56. Microsomal fractions provided greater cytochrome P-450 dependent activation of cyclophosphamide and were less cytotoxic than S9. 4. |
1(0,0,0,1) | Details |
| 19017849 | Storme T, Deroussent A, Mercier L, Prost E, Re M, Munier F, Martens T, Bourget P, Vassal G, Royer J, Paci A: New ifosfamide analogs designed for lower associated neurotoxicity and nephrotoxicity with modified alkylating kinetics leading to enhanced in vitro anticancer activity. J Pharmacol Exp Ther. 2009 Feb;328(2):598-609. Epub 2008 Nov 18. Ifosfamide is a well known prodrug for cancer treatment with cytochrome P450 metabolism. Isophosphoramide mustard is the bisalkylating active metabolite, and acrolein is a urotoxic side product. |
1(0,0,0,1) | Details |
| 12105905 | Shaffer CL, Harriman S, Koen YM, Hanzlik RP: Formation of cyclopropanone during cytochrome P450-catalyzed N-dealkylation of a cyclopropylamine. J Am Chem Soc. 2002 Jul 17;124(28):8268-74. HPLC examination of incubation mixtures revealed three UV-absorbing metabolites: N-methylaniline (4), N-cyclopropylaniline (6a), and a metabolite (M1) tentatively identified as p--2a, in a 2:5:2 mole ratio, respectively. 2,4-Dinitrophenylhydrazine trapping indicated formation of equimolar with 6a; and acrolein were not detected. |
1(0,0,0,1) | Details |
| 16332414 | Kim YJ, Kim DG, Lee SH, Lee I: Wound-induced expression of the 5-hydroxylase gene in Camptotheca acuminata. Biochim Biophys Acta. 2006 Feb;1760(2):182-90. Epub 2005 Nov 10. 5-hydroxylase (F5H) is a cytochrome P450-dependent monooxygenase that catalyses the hydroxylation of coniferaldehyde and coniferyl leading to sinapic acid and syringyl lignin biosynthesis. |
1(0,0,0,1) | Details |
| 1358518 | Cochon AC, San Martin de Viale LC, Wainstok de Calmanovici R: Cyclophosphamide and its metabolite acrolein. Comp Biochem Physiol C. 1992 May;102(1):143-8. Time course induction of cytochrome P-450 content after administration of CP or PB was similar. 6. |
1(0,0,0,1) | Details |
| 11220664 | Hecht SS: Carcinogen biomarkers for lung or oral cancer chemoprevention trials. IARC Sci Publ. 2001;154:245-55. Biomarkers that are potentially practical for current application in chemoprevention trials are 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo [a] pyrene-DNA adducts, as determined by HPLC with fluorescence detection, nitrosamino acids in urine, 4-(methylnitrosamino)-1-(3-pyridyl)- and its glucuronides in urine, metabolites in urine, and metabolites of cytochrome P450 substrates in urine. Biomarkers that need further development or exploration before application in trials include in DNA, tobacco-specific nitrosamine-DNA adducts, acrolein/crotonaldehyde-DNA adducts, PAH-protein adducts, -protein adducts, pyrene metabolites in urine and benzo [a] pyrene metabolites in urine. |
1(0,0,0,1) | Details |
| 2886311 | Rikans LE: The oxidation of acrolein by rat liver aldehyde dehydrogenases. Drug Metab Dispos. 1987 May-Jun;15(3):356-62. Hepatotoxicity was assessed on the basis of elevated serum alanine aminotransferase and sorbitol dehydrogenase activities and the loss of microsomal cytochrome P-450. |
1(0,0,0,1) | Details |
| 7710063 | Wright JE, Tretyakov O, Ayash LJ, Elias A, Rosowsky A, Frei E 3rd: Analysis of 4-hydroxycyclophosphamide in human blood. Anal Biochem. 1995 Jan 1;224(1):154-8. It was also used to measure the time-dependent disappearance of acrolein and 4-hydroxycyclophosphamide added to human blood from healthy donors and that of metabolically derived 4-hydroxycyclophosphamide in the blood of a patient treated with cyclophosphamide. Cyclophosphamide is a prodrug activated by cytochrome P450 isozymes in the liver. |
1(0,0,0,1) | Details |
| 4049387 | Ravindranath V, Boyd MR: Metabolic activation of 2-methylfuran by rat microsomal systems. Toxicol Appl Pharmacol. 1985 May;78(3):370-6. The microsomal metabolism of 2-MF was inducible by pretreatment of rats with phenobarbital and was inhibited by piperonyl butoxide and N-octyl which indicates that the metabolism of 2-MF may be mediated by cytochrome P-450. |
1(0,0,0,1) | Details |
| 9622079 | Egorin MJ, Rosen DM, Wolff JH, Callery PS, Musser SM, Eiseman JL: Metabolism of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) by murine and human hepatic preparations. Cancer Res. 1998 Jun 1;58(11):2385-96. Human microsomal metabolism of 17AAG was inhibited by ketoconazole, implying 3A4 as the responsible cytochrome P450 isoform. These data have implications with regard to preclinical toxicology and activity testing of 17AAG as well as its proposed clinical development because: (a) production of 17AG requires concomitant production of acrolein from the cleaved allyl moiety; and (b) 17AG, which was not metabolized by microsomes, has been described as being as active as 17AAG in decreasing cellular p185erbB2. |
1(0,0,0,1) | Details |
| 2118418 | LeBlanc GA, Waxman DJ: Mechanisms of cyclophosphamide action on hepatic P-450 expression. Cancer Res. 1990 Sep 15;50(18):5720-6. In vitro experiments revealed that P-450j was severalfold more susceptible to inactivation by the cyclophosphamide metabolite acrolein as compared with P-450 3. This decrease was due to the loss of cytochrome P-450 form 2c (IIC11), a major contributor to cyclophosphamide 4-hydroxylation in untreated male rat liver, while the other major hepatic cyclophosphamide 4-hydroxylase, P-450 PB-1 (IIC6), was largely unaffected. |
1(0,0,0,1) | Details |
| 7718306 | van Beerendonk GJ, Nelson SD, Meerman JH: Metabolism and genotoxicity of the halogenated alkyl compound tris (2,3-dibromopropyl) Hum Exp Toxicol. 1994 Dec;13(12):861-5. The use of completely deuterated Tris-BP as a metabolic probe revealed that cytochrome P450 and most likely the formation of 2-bromoacrolein (2BA) from Tris-BP is important for the observed genotoxic effects. 2. |
1(0,0,0,1) | Details |
| 10469623 | Yang Q, Hergenhahn M, Weninger A, Bartsch H: Cigarette smoke induces direct DNA damage in the human B-lymphoid cell line Raji. Carcinogenesis. 1999 Sep;20(9):1769-75. Most of the rapidly induced DNA damage was attributable to direct-acting compounds since cytochrome P450-related metabolic activities (ethoxy- and pentoxyresorufin-O-deethylases and coumarin-7-hydroxylase) were absent or very low. Among the CS constituents, acrolein, but not and induced DNA damage although less intensely than CS itself. |
1(0,0,0,1) | Details |
| 1611255 | Devaraj H, Niranjali S, Raveendran M: Effect of food flavor on liver microsomal cytochrome P-450 in rats. Bull Environ Contam Toxicol. 1992 Aug;49(2):306-11. |
1(0,0,0,1) | Details |
| 12615359 | Cheung C, Hotchkiss SA, Pease CK: Cinnamic compound metabolism in human skin and the role metabolism may play in determining relative sensitisation potency. J Dermatol Sci. 2003 Feb;31(1):9-19. Studies were conducted in the presence and absence of the ADH/cytochrome P450 inhibitor 4-methylpyrazole and the cytosolic ALDH inhibitor, disulfiram. |
1(0,0,0,1) | Details |