Alcohol-Metabolizing Enzymes, Liver Diseases and Cancer

被引：0
作者：
Liu, Tao [1 ,2 ,3 ]
Zhang, FeiYu [1 ,2 ,3 ]
Feng, Yue [1 ,2 ,3 ]
Han, PanShiLi [1 ,2 ,3 ]
Gao, YanHang [1 ,2 ,3 ]
机构：
[1] First Hosp Jilin Univ, Ctr Infect Dis & Pathogen Biol, Dept Hepatol, Changchun, Peoples R China
[2] China Singapore Belt & Rd Joint Lab Liver Dis Res, Changchun, Peoples R China
[3] Jilin Univ, Jilin Prov Key Lab Metab Liver Dis, Changchun, Peoples R China
来源：
SEMINARS IN LIVER DISEASE | 2025年
基金：
中国国家自然科学基金;
关键词：
ADH; ALDH; liver disease; liver cancer; ALDEHYDE DEHYDROGENASE 2; HEPATOCELLULAR-CARCINOMA; CYTOCHROME-P450; 2E1; FATTY LIVER; GENETIC POLYMORPHISMS; ETHANOL-METABOLISM; OXIDATIVE STRESS; INSULIN-RESISTANCE; ADH ISOENZYMES; MESSENGER-RNA;
D O I：
10.1055/a-2551-3320
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
Alcohol is generally believed to be metabolized in the liver by alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and to a much lesser extent cytochrome P450 2E1 (CYP2E1) and other enzymes. Recent studies suggest that gut also play important roles in the promotion of alcohol metabolism. ADH, ALDH, and CYP2E1 have several polymorphisms that markedly impact alcohol metabolism. These alcohol-metabolizing enzymes not only affect alcohol-associated liver disease (ALD), but may also modulate the pathogenesis of other liver diseases and cancer in the absence of alcohol consumption. In this review, we discuss alcohol metabolism and the roles of alcohol-metabolizing enzymes in the pathogenesis of ALD, metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction and alcohol-associated liver disease, viral hepatitis, and liver cancer. We also discuss how alcohol-metabolizing enzymes may affect endogenous ethanol production, and how ethanol metabolism in the gut affects liver disease and cancer. Directions for future research on the roles of alcohol- metabolizing enzymes in liver disease and cancer are also elaborated.
引用
收藏
页数：15
相关论文
共 175 条
  • [81] Zhou C., Lai Y., Huang P., Et al., Naringin attenuates alcoholic liver injury by reducing lipid accumulation and oxidative stress, Life Sci, 216, pp. 305-312, (2019)
  • [82] Liu Y.S., Yuan M.H., Zhang C.Y., Et al., Puerariae Lobatae radix flavonoids and puerarin alleviate alcoholic liver injury in zebra-fish by regulating alcohol and lipid metabolism, Biomed Pharmacother, 134, (2021)
  • [83] Hao L., Sun Q., Zhong W., Zhang W., Sun X., Zhou Z., Mitochondria-targeted ubiquinone (MitoQ) enhances acetaldehyde clearance by reversing alcohol-induced posttranslational modification of aldehyde dehydrogenase 2: a molecular mechanism of protection against alcoholic liver disease, Redox Biol, 14, pp. 626-636, (2018)
  • [84] Zhong W., Zhang W., Li Q., Et al., Pharmacological activation of aldehyde dehydrogenase 2 by Alda-1 reverses alcohol-induced hepatic steatosis and cell death in mice, J Hepatol, 62, pp. 1375-1381, (2015)
  • [85] Dolle L., Gao B., Pharmacological chaperone therapies: can aldehyde dehydrogenase activator make us healthier?, J Hepatol, 62, pp. 1228-1230, (2015)
  • [86] Younossi Z.M., Golabi P., Paik J.M., Henry A., Van Dongen C., Henry L., The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review, Hepatology, 77, pp. 1335-1347, (2023)
  • [87] Lieber C.S., The discovery of the microsomal ethanol oxidizing system and its physiologic and pathologic role, Drug Metab Rev, 36, 3-4, pp. 511-529, (2004)
  • [88] El-Khateeb E., Achour B., Al-Majdoub Z.M., Barber J., Rostami-Hodjegan A., Non-uniformity of changes in drug-metabolizing enzymes and transporters in liver cirrhosis: implications for drug dosage adjustment, Mol Pharm, 18, pp. 3563-3577, (2021)
  • [89] Fisher C.D., Lickteig A.J., Augustine L.M., Et al., Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease, Drug Metab Dispos, 37, 10, pp. 2087-2094, (2009)
  • [90] Zhu R., Baker S.S., Moylan C.A., Et al., Systematic transcriptome analysis reveals elevated expression of alcohol-metabolizing genes in NAFLD livers, J Pathol, 238, pp. 531-542, (2016)
45678910111213