Progress in research of phase Ⅱ metabolisms and their enzymes

Abstract

Abstract: Phase Ⅱ drug-metabolizing reaction, characterized by the conjugation reaction, is an important way of body drug disposition. Glucuronidation, acetylation, methylation, glutathione conjugation reaction, and sulphation represent different conjugation reactions and are catalyzed by some similar genes or gene superfamily respectively. All these phase Ⅱ metabolic reactions have their own different characteristics and functional significance. Drug induced significant change of phase Ⅱ drug metabolizing enzyme activity may lead to clinical drug interactions. The genetic polymorphisms of phase Ⅱdrug metabolizing enzymes will affect the metabolism of endogenous substances, which may lead to the increased incidence of certain diseases, and these polymorphisms also affect the metabolism of exogenous substances, causing toxicity or changes in drug efficacy.

Key words: Phase Ⅱ reaction, Phase Ⅱ metabolism enzyme, Drug metabolism

CLC Number:

R969

SHI Shu-ya, WANG Lian-sheng. Progress in research of phase Ⅱ metabolisms and their enzymes[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(1): 82-89.

References

[1] Sneitz N, Court MH, Zhang X, et al. Human UDP-glucuronosyltransferase UGT2A2: cDNA construction, expression, and functional characterization in comparison with UGT2A1 and UGT2A3[J]. Pharmacogenet Genomics, 2009, 19(12): 923-934.
[2] Xie T, Liang Y, Hao HP, et al. Advances in study of metabolic activation of carboxyl-acid containing drugs by UGTs[J]. Yao Xue Xue Bao, 2009, 44(11): 1193-1199.
[3] Uchaipichat V, Winner LK, Mackenzie PI, et al. Quantitative prediction of in vivo inhibitory interactions involving glucuronidated drugs from in vitro data: the effect of fluconazole on zidovudine glucuronidation[J]. Br J Clin Pharmacol, 2006, 61(4): 427-439.
[4] Miners JO, Bowalgaha K, Elliot DJ, et al. Characterization of niflumic acid as a selective inhibitor of human liver microsomal UDP-glucuronosyltransferase 1A9: application to the reaction phenotyping of acetaminophen glucuronidation[J]. Drug Metab Dispos, 2011, 39(4): 644-652.
[5] Uchaipichat V, Mackenzie PI, Elliot DJ, et al. Selectivity of substrate (trifluoperazine) and inhibitor (amitriptyline, androsterone, canrenoic acid, hecogenin, phenylbutazone, quinidine, quinine, and sulfinpyrazone) “probes” for human udp-glucuronosyltransferases[J]. Drug Metab Dispos, 2006, 34(3): 449-456.
[6] Reddy DS. Clinical pharmacokinetic interactions between antiepileptic drugs and hormonal contraceptives[J]. Expert Rev Clin Pharmacol, 2010, 3(2): 183-192.
[7] Toffoli G, Cecchin E, Corona G, et al. The role of UGT1A1*28 polymorphism in the pharmacodynamics and pharmacokinetics of irinotecan in patients with metastatic colorectal cancer[J]. J Clin Oncol, 2006, 24(19): 3061-3068.
[8] Erickson-Ridout KK, Zhu J, Lazarus P. Olanzapine metabolism and the significance of UGT1A448V and UGT2B1067Y variants[J]. Pharmacogenet Genomics, 2011, 21(9): 539-551.
[9] Gulcebi MI, Ozkaynakci A, Goren MZ, et al. The relationship between UGT1A4 polymorphism and serum concentration of lamotrigine in patients with epilepsy[J]. Epilepsy Res, 2011, 95(1/2): 1-8.
[10] Kukongviriyapan V, Phromsopha N, Tassaneeyakul W, et al. Inhibitory effects of polyphenolic compounds on human arylamine N-acetyltransferase 1 and 2[J]. Xenobiotica, 2006, 36(1): 15-28.
[11] Tiang JM, Butcher NJ, Minchin RF. Small molecule inhibition of arylamine N-acetyltransferase Type I inhibits proliferation and invasiveness of MDA-MB-231 breast cancer cells[J]. Biochem Biophys Res Commun, 2010, 393(1): 95-100.
[12] Ragunathan N, Dairou J, Pluvinage B, et al. Identification of the xenobiotic-metabolizing enzyme arylamine N-acetyltransferase 1 as a new target of cisplatin in breast cancer cells: molecular and cellular mechanisms of inhibition[J]. Mol Pharmacol, 2008, 73(6): 1761-1768.
[13] Hein DW. N-acetyltransferase SNPs: emerging concepts serve as a paradigm for understanding complexities of personalized medicine[J]. Expert Opin Drug Metab Toxicol, 2009, 5(4): 353-366.
[14] Walraven JM, Trent JO, Hein DW. Structure-function analyses of single nucleotide polymorphisms in human N-acetyltransferase 1[J]. Drug Metab Rev, 2008, 40(1): 169-184.
[15] Yassine IA, Kobeissi L, Jabbour ME, et al. N-Acetyltransferase 1 (NAT1) genotype: a risk factor for urinary bladder cancer in a lebanese population[J]. J Oncol, 2012, 2012: 512976.
[16] Paterson S, Sin KL, Tiang JM, et al. Histone deacetylase inhibitors increase human arylamine N-acetyltransferase-1 expression in human tumor cells[J]. Drug Metab Dispos, 2011, 39(1): 77-82.
[17] Klimcakova L, Habalova V, Sivonova M, et al. Effect of NAT2 gene polymorphism on bladder cancer risk in Slovak population[J]. Mol Biol Rep, 2011, 38(2): 1287-1293.
[18] Taspinar M, Ilgaz S, Ozdemir M, et al. Effect of lomeguatrib-temozolomide combination on MGMT promoter methylation and expression in primary glioblastoma tumor cells[J]. Tumour Biol, 2013, 34(3): 1935-1947.
[19] Hon YY, Jusko WJ, Spratlin VE, et al. Altered methylprednisolone pharmacodynamics in healthy subjects with histamine N-methyltransferase C314T genetic polymorphism[J]. J Clin Pharmacol, 2006, 46(4): 408-417.
[20] Wang Y, Fang Y, Shen Y, et al. Analysis of association between the catechol-O-methyltransferase (COMT) gene and negative symptoms in chronic schizophrenia[J]. Psychiatry Res, 2010, 179(2): 147- 150.
[21] Benedetti F, Dallaspezia S, Colombo C, et al. Effect of catechol-O-methyltransferase Val(108/158) Met polymorphism on antidepressant efficacy of fluvoxamine[J]. Eur Psychiatry, 2010, 25(8): 476-478.
[22] van Bladeren PJ. Glutathione conjugation as a bioactivation reaction[J]. Chem Biol Interact, 2000, 129(1/2): 61-76.
[23] Sheehan D, Meade G, Foley VM, et al. Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily[J]. Biochem J, 2001, 360(Pt 1): 1-16.
[24] Gao SS, Chen XY, Zhu RZ, et al. Sulforaphane induces glutathione S-transferase isozymes which detoxify aflatoxin B(1)-8,9-epoxide in AML 12 cells[J]. Biofactors, 2010, 36(4): 289-296.
[25] Liu XP, Goldring CE, Wang HY, et al. Extract of Ginkgo biloba induces glutathione-S-transferase subunit-P1 in vitro[J]. Phytomedicine, 2009, 16(5): 451-455.
[26] Hayeshi R, Mutingwende I, Mavengere W, et al. The inhibition of human glutathione S-transferases activity by plant polyphenolic compounds ellagic acid and curcumin[J]. Food Chem Toxicol, 2007, 45(2): 286-295.
[27] Safarinejad MR, Shafiei N, Safarinejad SH. Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and prostate cancer: a case-control study in Tehran, Iran[J]. Prostate Cancer Prostatic Dis, 2011, 14(2): 105-113.
[28] Vreuls CP, Olde DS, Koek GH, et al. Glutathione S-transferase M1-null genotype as risk factor for SOS in oxaliplatin-treated patients with metastatic colorectal cancer[J]. Br J Cancer, 2013, 108(3): 676- 680.
[29] Backos DS, Franklin CC, Reigan P. The role of glutathione in brain tumor drug resistance[J]. Biochem Pharmacol, 2012, 83(8): 1005-1012.
[30] Senggunprai L, Yoshinari K, Yamazoe Y. Selective role of sulfotransferase 2A1 (SULT2A1) in the N-sulfoconjugation of quinolone drugs in humans[J]. Drug Metab Dispos, 2009, 37(8): 1711-1717.
[31] Surh YJ. Bioactivation of benzylic and allylic alcohols via sulfo-conjugation[J]. Chem Biol Interact, 1998, 109(1/2/3): 221-235.
[32] Strassburg CP, Strassburg A, Kneip S, et al. Developmental aspects of human hepatic drug glucuronidation in young children and adults[J]. Gut, 2002, 50(2): 259-265.
[33] Fournel-Gigleux S, Coughtrie MW, Ouzzine M, et al. The use of hepatocytes to investigate UDP-glucuronosyltransferases and sulfotransferases[J]. Methods Mol Biol, 2010, 640: 309-326.
[34] Schwaninger AE, Meyer MR, Zapp J, et al. Sulfation of the 3,4-methylenedioxymethamphetamine (MDMA) metabolites 3,4-dihydroxymethamphetamine (DHMA) and 4-hydroxy-3-methoxymethampheta- mine (HMMA) and their capability to inhibit human sulfotransferases[J]. Toxicol Lett, 2011, 202(2): 120-128.
[35] Eagle K. Toxicological effects of red wine, orange juice, and other dietary SULT1A inhibitors via excess catecholamines[J]. Food Chem Toxicol, 2012, 50(6): 2243-2249.
[36] King RS, Ghosh AA, Wu J. Inhibition of human phenol and estrogen sulfotransferase by certain non-steroidal anti-inflammatory agents[J]. Curr Drug Metab, 2006, 7(7): 745-753.
[37] Maiti S, Chen X, Chen G. All-trans retinoic acid induction of sulfotransferases[J]. Basic Clin Pharmacol Toxicol, 2005, 96(1): 44-53.
[38] Chen X, Baker SM, Chen G. Methotrexate induction of human sulfotransferases in Hep G2 and Caco-2 cells[J]. J Appl Toxicol, 2005, 25(5): 354-360.
[39] Santos SS, Koifman RJ, Ferreira RM, et al. SULT1A1 genetic polymorphisms and the association between smoking and oral cancer in a case-control study in Brazil[J]. Front Oncol, 2012, 2: 183.
[40] Liu Q, Ramsey TL, Meltzer HY, et al. Sulfotransferase 4A1 haplotype 1 (SULT4A1-1) is associated with decreased hospitalization events in antipsychotic-treated patients with schizophrenia[J]. Prim Care Companion CNS Disord, 2012, 14(3).
[41] Hashiguchi T, Kurogi K, Sakakibara Y, et al. Enzymatic sulfation of tocopherols and tocopherol metabolites by human cytosolic sulfotransferases[J]. Biosci Biotechnol Biochem, 2011, 75(10): 1951-1956.
[42] Runge-Morris M, Kocarek TA. Regulation of sulfotransferase and UDP-glucuronosyltransferase gene expression by the PPARs[J]. PPAR Res, 2009, 2009: 728941.
[43] Takahashi S, Sakakibara Y, Mishiro E, et al. Molecular cloning, expression and characterization of a novel mouse SULT6 cytosolic sulfotransferase[J]. J Biochem, 2009, 146(3): 399-405.
[44] 张艳, 郝海平, 王广基. 尿苷二磷酸葡萄糖醛酸转移酶介导的药物相互作用的研究进展[J]. 中国临床药理学与治疗学, 2011, 16(4): 447-454.