Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland.
Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, 02-089 Warsaw, Poland.
Biomolecules. 2024 Jul 19;14(7):869. doi: 10.3390/biom14070869.
Molybdenum (Mo) is an essential element for human life, acting as a cofactor in various enzymes crucial for metabolic homeostasis. This review provides a comprehensive insight into the latest advances in research on molybdenum-containing enzymes and their clinical significance. One of these enzymes is xanthine oxidase (XO), which plays a pivotal role in purine catabolism, generating reactive oxygen species (ROS) capable of inducing oxidative stress and subsequent organ dysfunction. Elevated XO activity is associated with liver pathologies such as non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Aldehyde oxidases (AOs) are also molybdenum-containing enzymes that, similar to XO, participate in drug metabolism, with notable roles in the oxidation of various substrates. However, beneath its apparent efficacy, AOs' inhibition may impact drug effectiveness and contribute to liver damage induced by hepatotoxins. Another notable molybdenum-enzyme is sulfite oxidase (SOX), which catalyzes the conversion of sulfite to sulfate, crucial for the degradation of sulfur-containing amino acids. Recent research highlights SOX's potential as a diagnostic marker for HCC, offering promising sensitivity and specificity in distinguishing cancerous lesions. The newest member of molybdenum-containing enzymes is mitochondrial amidoxime-reducing component (mARC), involved in drug metabolism and detoxification reactions. Emerging evidence suggests its involvement in liver pathologies such as HCC and NAFLD, indicating its potential as a therapeutic target. Overall, understanding the roles of molybdenum-containing enzymes in human physiology and disease pathology is essential for advancing diagnostic and therapeutic strategies for various health conditions, particularly those related to liver dysfunction. Further research into the molecular mechanisms underlying these enzymes' functions could lead to novel treatments and improved patient outcomes.
钼(Mo)是人体生命必需的元素,作为各种代谢稳态关键酶的辅因子发挥作用。本综述全面介绍了含钼酶的最新研究进展及其临床意义。这些酶之一是黄嘌呤氧化酶(XO),它在嘌呤分解代谢中起着关键作用,生成能够诱导氧化应激和随后的器官功能障碍的活性氧(ROS)。XO 活性升高与肝脏病变有关,如非酒精性脂肪性肝病(NAFLD)和肝细胞癌(HCC)。醛氧化酶(AOs)也是含钼酶,与 XO 相似,参与药物代谢,在各种底物的氧化中起重要作用。然而,在其明显的疗效之下,AOs 的抑制可能会影响药物的有效性,并导致肝毒素引起的肝损伤。另一种值得注意的含钼酶是亚硫酸氧化酶(SOX),它催化亚硫酸盐转化为硫酸盐,这对含硫氨基酸的降解至关重要。最近的研究强调了 SOX 作为 HCC 诊断标志物的潜力,在区分癌性病变方面具有很高的灵敏度和特异性。含钼酶的最新成员是线粒体酰胺氧化还原酶(mARC),它参与药物代谢和解毒反应。新出现的证据表明其与 HCC 和 NAFLD 等肝脏病变有关,表明其作为治疗靶点的潜力。总之,了解含钼酶在人体生理和疾病病理中的作用对于推进各种健康状况(特别是与肝功能障碍相关的状况)的诊断和治疗策略至关重要。对这些酶功能的分子机制的进一步研究可能会导致新的治疗方法和改善患者的预后。