尿酸氧化酶降解尿酸作用机理及应用的文献计量学可视化分析

Bibliometric visualization analysis of the mechanism and applications of urate oxidase in uric acid degradation

摘要

尿酸氧化酶(Urate oxidase)是生物嘌呤代谢途径中的一种关键酶,可降低人体内尿酸含量,缓解和治疗由高尿酸引起的一系列疾病。本文采用文献计量学的方法对尿酸氧化酶相关文献进行了系统的分析和总结。通过对Web of Science Core Collection数据库中1980—2024年发表的2240篇尿酸氧化酶相关文献进行系统分析,发现2000年开始,研究者们对尿酸氧化酶的关注度越来越高,并对其展开了大量的研究。其中美国是发表文章最多的国家,重庆医科大学是发文量最突出的机构。Sensors and Actuators B-Chemical和Biosensors & Bioelectronic分别是发文量最高(36篇)和引用次数最多(2488次)的期刊。高被引文献分析显示,尿酸氧化酶相关主题关注度最高的是“高尿酸血症”、“拉布立酶”、“尿酸氧化酶结构及进化意义”。关键词聚类(uric acid、urate oxidase、hyperuricemia、gout、electrochemical biosensor)揭示了尿酸氧化酶从基础代谢机制(将尿酸氧化成尿囊素、过氧化氢和二氧化碳),到病理表型(高尿酸血症、痛风等),再到技术创新(生物传感器应用)的完整链条,为疾病研究、诊断工具开发及精准治疗提供了系统性视角。本研究以宏观的角度对尿酸氧化酶进行系统阐述,为后续的研究工作提供极具价值的指引方向。

Abstract

Urate oxidase, a key enzyme in the biological purine metabolism pathway, reduces the level of uric acid in the body and alleviates and treats a range of diseases caused by high uric acid. In this paper, the literature related to urate oxidase was systematically analyzed and summarized using bibliometric methods. A systematic analysis of 2240 urate oxidase-related papers published from 1980 to 2024 in the Web of Science Core Collection database revealed that researchers have been paying more attention to urate oxidase since 2000 and have conducted a large number of studies on it. The United States ranks as the country with the highest number of published articles, while Chongqing Medical University stands out as the institution with the most significant output. Sensors and Actuators B-Chemical and Biosensors & Bioelectronic were the journals with the highest number of articles (36) and citations (2488), respectively. Analysis of the highly cited literature shows that the topics of highest interest related to urate oxidase are “hyperuricemia” “rasburicase” and “Structure and evolutionary significance of urate oxidase”. Keyword clustering (uric acid, urate oxidase, hyperuricemia, gout, electrochemical biosensor) reveals the complete chain of urate oxidase from the underlying metabolic mechanism (oxidation of uric acid into allantoin, hydrogen peroxide, and carbon dioxide), to pathological phenotypes (hyperuricemia, gout, etc.), and to technological innovations (biologic sensor applications), providing a systematic perspective for disease research, diagnostic tool development and precision therapy. The present study provides a systematic description of urate oxidase from a macroscopic point of view, which will provide a valuable guideline for subsequent research.

关键词

尿酸氧化酶 / 尿酸 / 尿囊素 / 高尿酸血症 / 文献计量学

Key words

urate oxidase / uric acid / allantoin / hyperuricemia / bibliometrics

参考文献

[1] GIORDANO C, KARASIK O, KING—MORRIS K, et al. Uric acid as a marker of kidney disease: Review of the current literature[J]. Disease Markers, 2015, 2015(1): 382918.

[2] CABĂU G, CRIȘAN TO, KLÜCK V, et al. Urate—induced immune programming: Consequences for gouty arthritis and hyperuricemia[J]. Immunological Reviews, 2020, 294(1): 92-105.

[3] MANDAL A K, MOUNT D B. The molecular physiology of uric acid homeostasis[J]. Annual Review of Physiology, 2015, 77: 323-345.

[4] HAFEZ R M, ABDEL—RAHMAN T M, NAGUIB R M. Uric acid in plants and microorganisms: Biological applications and genetics—A review[J]. Journal of Advanced Research, 2017, 8(5): 475-486.

[5] GHERGHINA M E, PERIDE I, TIGLIS M, et al. Uric acid and oxidative stress—relationship with cardiovascular, metabolic, and renal impairment[J]. International Journal of Molecular Sciences, 2022, 23(6): 3188.

[6] FATHALLAH—SHAYKH S A, CRAMER M T. Uric acid and the kidney[J]. Pediatric Nephrology, 2014, 29(6): 999-1008.

[7] ICHIDA K, MATSUO H, TAKADA T, et al. Decreased extra—renal urate excretion is a common cause of hyperuricemia[J]. Nature Communications, 2012, 3: 764.

[8] YANAI H, ADACHI H, HAKOSHIMA M, et al. Molecular biological and clinical understanding of the pathophysiology and treatments of hyperuricemia and its association with metabolic syndrome, cardiovascular diseases and chronic kidney disease[J]. International Journal of Molecular Sciences, 2021, 22(17): 9221.

[9] CHEN G, TAN M L, LI K K, et al. Green tea polyphenols decreases uric acid level through xanthine oxidase and renal urate transporters in hyperuricemic mice[J]. Journal of Ethnopharmacology, 2015, 175: 14-20.

[10] CHOI Y J, YOON Y, LEE K Y, et al. Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis[J]. The FASEB Journal, 2014, 28(7): 3197-3204.

[11] YAO T K, LEE R P, WU W T, et al. Advances in gouty arthritis management: integration of established therapies, emerging treatments, and lifestyle interventions[J]. International Journal of Molecular Sciences, 2024, 25(19): 10853.

[12] WU Z D, YANG X K, HE Y S, et al. Environmental factors and risk of gout[J]. Environmental Research, 2022, 212: 113377.

[13] LIN A Q, SUN Z Y, XU X Q, et al. Self—cascade uricase/catalase mimics alleviate acute gout[J]. Nano Letters, 2022, 22(1): 508-516.

[14] PASCART T, RICHETTE P. Investigational drugs for hyperuricemia, an update on recent developments[J]. Expert Opinion on Investigational Drugs, 2018, 27(5): 437-444.

[15] LIU C W, KE S R, TSENG G S, et al. Elevated serum uric acid is associated with incident hypertension in the health according to various contemporary blood pressure guidelines[J]. Nutrition, Metabolism, and Cardiovascular Diseases, 2021, 31(4): 1209-1218.

[16] SAPANKAEW T, THADANI PON K, RUENROENGBUN N, et al. Efficacy and safety of urate—lowering agents in asymptomatic hyperuricemia: Systematic review and network meta—analysis of randomized controlled trials[J]. BMC Nephrology, 2022, 23(1): 223.

[17] CHEUK D K L, CHIANG A K S, CHANG C F, et al. Urate oxidase for the prevention and treatment of tumour lysis syndrome in children with cancer[J]. The Cochrane Database of Systematic Reviews, 2014(8): CD006945.

[18] JEHA S, PUI C H. Recombinant urate oxidase (rasburicase) in the prophylaxis and treatment of tumor lysis syndrome[J]. Contributions to Nephrology, 2005, 147: 69-79.

[19] TERKELTAUB R. Emerging urate—lowering drugs and pharmacologic treatment strategies for gout: a narrative review[J]. Drugs, 2023, 83(16): 1501-1521.

[20] LEE I R, YANG L T, SEBETSO G, et al. Characterization of the complete uric acid degradation pathway in the fungal pathogen Cryptococcus neoformans[J]. PLoS One, 2013, 8(5): e64292.

[21] ZHANG R, GAO S J, ZHU C Y, et al. Characterization of a novel alkaline Arxula adeninivorans urate oxidase expressed in Escherichia coli and its application in reducing uric acid content of food[J]. Food Chemistry, 2019, 293: 254-262.

[22] KRATZER J T, LANASPA M A, MURPHY M N, et al. Evolutionary history and metabolic insights of ancient mammalian uricases[J]. Proceedings of the National Academy of Science, 2014, 111(10): 3763-3768.

[23] WU X W, LEE C C, MUZNY D M, et al. Urate oxidase: Primary structure and evolutionary implications[J]. Proceedings of the National Academy of Sciences of the United States of America, 1989, 86(23): 9412-9416.

[24] XIAN J N, GUO X, LI B, et al. Screening, characterization and expression of microbial urate oxidase[J]. Chinese Journal of Biotechnology, 2018, 34(7): 1147-1155.

[25] HAFEZ R M, ABDEL—RAHMAN T M, NAGUIB R M. Uric acid in plants and microorganisms: Biological applications and genetics—A review[J]. Journal of Advanced Research, 2017, 8(5): 475-486.

[26] YIM B T, SIMS—MCCALLUM R P, CHONG P H. Rasburicase for the treatment and prevention of hyperuricemia[J]. The Annals of Pharmacotherapy, 2003, 37(7/8): 1047-1054.

[27] SCHLESINGER N, LIPSKY P E. Pegloticase treatment of chronic refractory gout: Update on efficacy and safety[J]. Seminars in Arthritis and Rheumatism, 2020, 50(3): S31-S38.

[28] PUI C H, MAHMOUD H H, WILEY J M, et al. Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients with leukemia or lymphoma[J]. Journal of Clinical Oncology, 2001, 19(3): 697-704.

[29] GOLDMAN S C, HOLCENBERG J S, FINKLESTEIN J Z, et al. A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis[J]. Blood, 2001, 97(10): 2998-3003.

[30] WU X W, MUZNY D M, CHI LEE C, et al. Two independent mutational events in the loss of urate oxidase during hominoid evolution[J]. Journal of Molecular Evolution, 1992, 34(1): 78-84.

[31] WU X W, LEE C C, MUZNY D M, et al. Urate oxidase: Primary structure and evolutionary implications[J]. Proceedings of the National Academy of Sciences of the United States of America, 1989, 86(23): 9412-9416.

[32] ODA M, SATTA Y, TAKENAKA O, et al. Loss of urate oxidase activity in hominoids and its evolutionary implications[J]. Molecular Biology and Evolution, 2002, 19(5): 640-653.

[33] COIFFIER B, MOUNIER N, BOLOGNA S, et al. Efficacy and safety of rasburicase (recombinant urate oxidase) for the prevention and treatment of hyperuricemia during induction chemotherapy of aggressive non—Hodgkin’s lymphoma: Results of the GRAAL1 (Groupe d’Etude des Lymphomes de l’Adulte Trial on Rasburicase Activity in Adult Lymphoma) study[J]. Journal of Clinical Oncology, 2003, 21(23): 4402-4406.

[34] CAIRO M S, BISHOP M. Tumour lysis syndrome: New therapeutic strategies and classification[J]. British Journal of Haematology, 2004, 127(1): 3-11.

[35] COLLOC’H N, EL HAJJI M, BACHET B, et al. Crystal Structure of the protein drug urate oxidase—inhibitor complex at 2.05 Å resolution[J]. Nature Structural Biology, 1997, 4(11): 947-952.

[36] PUI C H, RELLING M, LASCOMBES F, et al. Urate oxidase in prevention and treatment of hyperuricemia associated with lymphoid malignancies[J]. Leukemia, 1997, 11(11): 1813-1816.

[37] WU X, WAKAMIYA M, VAISHNAV S, et al. Hyperuricemia and urate nephropathy in urate oxidase—deficient mice.[J]. Proceedings of the National Academy of Sciences of the United States of America, 1994, 91(2): 742-746.

[38] CLEVELAND B M, LEONARD S S, KLANDORF H, et al. Urate oxidase knockdown decreases oxidative stress in a murine hepatic cell line[J]. Oxidative Medicine and Cellular Longevity, 2009, 2(2): 93-98.

[39] RODRIGUEZ M, CAMPARA M, HAAF C. Rasburicase in cancer—related hyperuricemia[J]. Drugs of Today, 2011, 47(8): 591-603.

[40] WEI D H, HUANG X Q, QIAO Y, et al. Catalytic mechanisms for cofactor—free oxidase—catalyzed reactions: Reaction pathways of uricase—catalyzed oxidation and hydration of uric acid[J]. ACS Catalysis, 2017, 7(7): 4623-4636.

[41] ZHAO R, LI Z M, SUN Y Q, et al. Engineered Escherichia coli Nissle 1917 with urate oxidase and an oxygen—recycling system for hyperuricemia treatment[J]. Gut Microbes, 2022, 14(1): 2070391.

[42] HAYASHI H. Degradation of peroxisomal catalase and urate oxidase of rat liver[J]. Biochimica et Biophysica Acta (BBA)—General Subjects, 1979, 585(2): 220-228.

[43] CORTES J, MOORE J O, MAZIARZ R T, et al. Control of plasma uric acid in adults at risk for tumor Lysis syndrome: Efficacy and safety of rasburicase alone and rasburicase followed by allopurinol compared with allopurinol alone—results of a multicenter phase III study[J]. Journal of Clinical Oncology, 2010, 28(27): 4207-4213.

[44] ZHAO R C, ZHANG Y M, RUAN B L, et al. Nanourchin—like uricase—poly(L—proline) conjugate with retained enzymatic activity, mitigated immunogenicity, and sustained efficacy upon repeated administrations[J]. Angewandte Chemie International Edition, 2025, 64(20): e202425559.

[45] WANG Q W, WEN X, KONG J M. Recent progress on uric acid detection: A review[J]. Critical Reviews in Analytical Chemistry, 2020, 50(4): 359-375.

[46] LIANG X, CHEN Y X, WEN K, et al. Urate oxidase loaded in PCN—222(Fe) with peroxidase—like activity for colorimetric detection of uric acid[J]. Journal of Materials Chemistry B, 2021, 9(34): 6811-6817.

[47] FALO HU N T, MCSHANE M J. An optical urate biosensor based on urate oxidase and long—lifetime metalloporphyrins[J]. Sensors, 2020, 20(4): 959.

[48] LU F, YANG Y L, LIU Y C, et al. Point—of—care testing (POCT) of patients with a high concentration of uric acid by using alginate hydrogel microspheres embedded with CdZnTeS QDs and urate oxidase (Alg@QDs—UOxMSs)[J]. Analyst, 2021, 146(3): 949-955.

[49] YANG M, SUN Z J, JIN H, et al. Urate oxidase—loaded MOF electrodeposited on boron nanosheet—doxorubicin complex as multifunctional nano—enzyme platform for enzymatic and ratiometric electrochemical biosensing[J]. Talanta, 2022, 243: 123359.

[50] KOYAMA Y, ICHIKAWA T, NAKANO E. Cloning, sequence analysis, and expression in Escherichia coli of the gene encoding the Candida utilis urate oxidase (uricase)[J]. Journal of Biochemistry, 1996, 120(5): 969-973.

[51] MAHMOUD H, LEVERGER G, PATTE C, et al. Advances in the management of malignancy—associated hyperuricaemia[J]. British Journal of Cancer, 1998, 77(4): 18-20.

[52] CHIU Y C, HSU T S, HUANG C Y, et al. Molecular elucidation of a urate oxidase from Deinococcus radiodurans for hyperuricemia and gout therapy[J]. International Journal of Molecular Sciences, 2021, 22(11): 5611.

基金资助

齐鲁工业大学(山东省科学院)重点创新项目(2024ZDZX03)

齐鲁工业大学(山东省科学院)科教产融合试点工程重大创新专项(2025ZDZX14)

中央引导地方科技发展专项基金项目(YDZX2024015)

中央引导地方科技发展专项基金项目(YDZX2023006)

2023年省级重点研发计划(乡村振兴科技创新促进计划)(2023TZXD003)