维基百科

眼晶体酸

化合物

眼晶体酸[1]或视晶酸（英语：Ophthalmic acid，ophthalmate，缩写OPH）是一种三肽，从化学结构上可称为L-γ-谷氨酰-L-α-氨基丁酰基甘氨酸。其为谷胱甘肽的类似物，与谷胱甘肽的区别在于将结构中半胱氨酸替换成了L-2-氨基丁酸。L-2-氨基丁酸是一种非蛋白质氨基酸，其没有半胱氨酸所具备的亲核性巯基，同时巯基也是谷胱甘肽各种重要功能的来源基团，因此眼晶体酸曾一度被错误地视为生物合成谷胱甘肽过程中产生的错误副产物。

眼晶体酸
IUPAC名
(N-(L-γ-Glutamyl)-(2S)-2-aminobutyryl)glycine
别名 视晶酸
识别
CAS号 495-27-2  checkY
PubChem 7018721
ChemSpider 5381695
SMILES
 
  • CC[C@H](NC(=O)CC[C@H](N)C(O)=O)C(=O)NCC(O)=O
ChEBI 84058
MeSH ophthalmic+acid
性质
化学式 C11H19N3O6
摩尔质量 289.29 g·mol−1
外观 白色晶体
若非注明，所有数据均出自标准状态（25 ℃，100 kPa）下。

2024年，Schomakers等人根据已有研究，提出了眼晶体酸是谷胱甘肽的一种调节因子的假设。其认为眼晶体酸作为谷胱甘肽调节三肽，影响细胞和细胞器谷胱甘肽的流入和流出，并调节与谷胱甘肽有关的反应和信号传导[2]。

生物合成

眼晶体酸由2-氨基丁酸作为原料合成，其涉及的酶和生产谷胱甘肽的酶一样，都是谷氨酸-半胱氨酸连接酶（英语：Glutamate–cysteine ligase）和谷胱甘肽合成酶（英语：Glutathione synthetase）。影响眼晶体酸生物合成的主要因素是半胱氨酸和2-氨基丁酸的局部相对浓度，以及它们的γ-谷氨酰中间产物[2]。

发现与分布

眼晶体酸最早于1956年在牛犊的晶状体中发现[3]。此后发现其是一种在普遍存在的代谢物。各种生物体中都发现了眼晶体酸，包括：

在高度动物体内各种器官组织中也广泛分布：包括大脑[16] 、眼[16] 、肝[16][14]、肾脏[14]、心脏[17]、生殖腺[32]、卵巢[24] 、肌肉[19]、脂肪组织[33]、血液[22]、血浆[34]、红细胞[15]以及粪便[9]。

在植物中，其存在于种子[7]、叶片[7]、果肉[8]、豆荚[9]等部位。

氧化应激标志争论

在2006年一项在小鼠施加过量对乙酰氨基酚的代谢学研究中，眼晶体酸经常别视为一种氧化应激标志物，将其浓度改变行为与受到氧化应激联系起来[34]。然而不同学者对其持有不同意见：

即使观测到了两者之间的相对变化[7][35]，但不意味着眼晶体酸增加与谷胱甘肽减少之间没有相关性。相对于健康标准值，两者可同增[13][23]同减[36][37]，或者眼晶体酸单独增加[24][38][11]。一项眼晶体酸与谷胱甘肽的昼夜节律追踪实验显示：眼晶体酸浓度有昼夜节律然而谷胱甘肽没有[39]。在同一时间，同一动物的不同组织之间眼晶体酸水平变化趋势的也有很大差异[40][41]。这些研究结果均表明眼晶体酸与谷胱甘肽之间没有相关性。

而且也有研究发现眼晶体酸在正常的组织中含量也很高，比如眼睛中，意味着其不仅仅存在于受到应激和疾病的组织中[29]。

后续也有研究推翻了2006年的小鼠实验，证实其研究方法不可靠[42][40]。

参考文献

  1. ^ 苏子仁，赖小平 (编). 汉英、英汉中草药化学成分词汇. 北京: 中国中医药出版社. 2006. ISBN 9787801569103. 
  2. ^ 2.0 2.1 Schomakers, Bauke V.; Jillings, Sonia L.; van Weeghel, Michel; Vaz, Frédéric M.; Salomons, Gajja S.; Janssens, Georges E.; Houtkooper, Riekelt H. Ophthalmic acid is a glutathione regulating tripeptide. The FEBS Journal. 2024-01-20 [2024-07-24]. ISSN 1742-464X. doi:10.1111/febs.17061  . （原始内容存档于2024-03-10） （英语）. 
  3. ^ Waley SG; Biochem. J. 64, 715 (1956)
  4. ^ Narainsamy, Kinsley; Farci, Sandrine; Braun, Emilie; Junot, Christophe; Cassier‐Chauvat, Corinne; Chauvat, Franck. Oxidative‐stress detoxification and signalling in cyanobacteria: the crucial glutathione synthesis pathway supports the production of ergothioneine and ophthalmate. Molecular Microbiology. 2016-02-09, 100 (1): 15–24. ISSN 0950-382X. doi:10.1111/mmi.13296  . 
  5. ^ Ito, Tomokazu; Yamauchi, Ayako; Hemmi, Hisashi; Yoshimura, Tohru. Ophthalmic acid accumulation in an Escherichia coli mutant lacking the conserved pyridoxal 5′-phosphate-binding protein YggS. Journal of Bioscience and Bioengineering. December 2016, 122 (6): 689–693. ISSN 1389-1723. doi:10.1016/j.jbiosc.2016.06.010. 
  6. ^ Fountain, Jake C.; Yang, Liming; Pandey, Manish K.; Bajaj, Prasad; Alexander, Danny; Chen, Sixue; Kemerait, Robert C.; Varshney, Rajeev K.; Guo, Baozhu. Carbohydrate, glutathione, and polyamine metabolism are central to Aspergillus flavus oxidative stress responses over time. 2019-01-03 [2023-11-18]. doi:10.1101/511170. 
  7. ^ 7.0 7.1 7.2 7.3 Servillo, Luigi; Castaldo, Domenico; Giovane, Alfonso; Casale, Rosario; D'Onofrio, Nunzia; Cautela, Domenico; Balestrieri, Maria Luisa. Ophthalmic acid is a marker of oxidative stress in plants as in animals. Biochimica et Biophysica Acta (BBA) - General Subjects. April 2018, 1862 (4): 991–998. ISSN 0304-4165. doi:10.1016/j.bbagen.2018.01.015. 
  8. ^ 8.0 8.1 Pinsorn, Pinnapat; Oikawa, Akira; Watanabe, Mutsumi; Sasaki, Ryosuke; Ngamchuachit, Panita; Hoefgen, Rainer; Saito, Kazuki; Sirikantaramas, Supaart. Metabolic variation in the pulps of two durian cultivars: Unraveling the metabolites that contribute to the flavor. Food Chemistry. December 2018, 268: 118–125. ISSN 0308-8146. doi:10.1016/j.foodchem.2018.06.066. 
  9. ^ 9.0 9.1 9.2 9.3 Baxter, Bridget; Oppel, Renee; Ryan, Elizabeth. Navy Beans Impact the Stool Metabolome and Metabolic Pathways for Colon Health in Cancer Survivors. Nutrients. 2018-12-22, 11 (1): 28. ISSN 2072-6643. PMC 6356708  . doi:10.3390/nu11010028  . 
  10. ^ Schomakers, Bauke V.; Hermans, Jill; Jaspers, Yorrick R.J.; Salomons, Gajja; Vaz, Frédéric M.; van Weeghel, Michel; Houtkooper, Riekelt H. Polar metabolomics in human muscle biopsies using a liquid-liquid extraction and full-scan LC-MS. STAR Protocols. June 2022, 3 (2): 101302. ISSN 2666-1667. PMC 9035783  . doi:10.1016/j.xpro.2022.101302  . 
  11. ^ 11.0 11.1 Ryabova, Alina; Cornette, Richard; Cherkasov, Alexander; Watanabe, Masahiko; Okuda, Takashi; Shagimardanova, Elena; Kikawada, Takahiro; Gusev, Oleg. Combined metabolome and transcriptome analysis reveals key components of complete desiccation tolerance in an anhydrobiotic insect. Proceedings of the National Academy of Sciences. 2020-07-28, 117 (32): 19209–19220. ISSN 0027-8424. PMC 7431039  . doi:10.1073/pnas.2003650117  . 
  12. ^ Remø, Sofie Charlotte; Hevrøy, Ernst Morten; Breck, Olav; Olsvik, Pål Asgeir; Waagbø, Rune. Lens metabolomic profiling as a tool to understand cataractogenesis in Atlantic salmon and rainbow trout reared at optimum and high temperature. PLOS ONE. 2017-04-18, 12 (4): e0175491. ISSN 1932-6203. PMC 5395160  . doi:10.1371/journal.pone.0175491  . 
  13. ^ 13.0 13.1 Abasht, Behnam; Mutryn, Marie F.; Michalek, Ryan D.; Lee, William R. Oxidative Stress and Metabolic Perturbations in Wooden Breast Disorder in Chickens. PLOS ONE. 2016-04-20, 11 (4): e0153750. ISSN 1932-6203. PMC 4838225  . doi:10.1371/journal.pone.0153750  . 
  14. ^ 14.0 14.1 14.2 Orlowski, M; Wilk, S. Synthesis of ophthalmic acid in liver and kidney in vivo. Biochemical Journal. 1978-02-15, 170 (2): 415–419. ISSN 0306-3283. PMC 1183909  . PMID 637852. doi:10.1042/bj1700415. 
  15. ^ 15.0 15.1 Andres Ibarra, Rafael; Abbas, R.; Kombu, R. S.; Zhang, Guo-Fang; Jacobs, G.; Lee, Z.; Brunengraber, H.; Sanabria, J. R. Disturbances in the Glutathione/Ophthalmate Redox Buffer System in the Woodchuck Model of Hepatitis Virus-Induced Hepatocellular Carcinoma. HPB Surgery. 2011-09-18, 2011: 1–9. ISSN 0894-8569. PMC 3175733  . doi:10.1155/2011/789323  . 
  16. ^ 16.0 16.1 16.2 16.3 16.4 16.5 Tsuboi, Seiji; Hirota, Kazuhiro; Ogata, Kazumi; Ohmori, Shinji. Ophthalmic and norophthalmic acid in lens, liver, and brain of higher animals. Analytical Biochemistry. February 1984, 136 (2): 520–524. ISSN 0003-2697. doi:10.1016/0003-2697(84)90255-0. 
  17. ^ 17.0 17.1 Maekawa, Keiko; Hirayama, Akiyoshi; Iwata, Yuko; Tajima, Yoko; Nishimaki-Mogami, Tomoko; Sugawara, Shoko; Ueno, Noriko; Abe, Hiroshi; Ishikawa, Masaki; Murayama, Mayumi; Matsuzawa, Yumiko; Nakanishi, Hiroki; Ikeda, Kazutaka; Arita, Makoto; Taguchi, Ryo. Global metabolomic analysis of heart tissue in a hamster model for dilated cardiomyopathy. Journal of Molecular and Cellular Cardiology. June 2013, 59: 76–85. ISSN 0022-2828. doi:10.1016/j.yjmcc.2013.02.008. 
  18. ^ Kombu, Rajan S.; Zhang, Guo-Fang; Abbas, Rime; Mieyal, John J.; Anderson, Vernon E.; Kelleher, Joanne K.; Sanabria, Juan R.; Brunengraber, Henri. Dynamics of glutathione and ophthalmate traced with2H-enriched body water in rats and humans. American Journal of Physiology. Endocrinology and Metabolism. July 2009, 297 (1): E260–E269. ISSN 0193-1849. PMC 2711657  . PMID 19401458. doi:10.1152/ajpendo.00080.2009. 
  19. ^ 19.0 19.1 Janssens, Georges E.; Grevendonk, Lotte; Perez, Ruben Zapata; Schomakers, Bauke V.; de Vogel-van den Bosch, Johan; Geurts, Jan M. W.; van Weeghel, Michel; Schrauwen, Patrick; Houtkooper, Riekelt H.; Hoeks, Joris. Healthy aging and muscle function are positively associated with NAD+ abundance in humans. Nature Aging. 2022-02-17, 2 (3): 254–263. ISSN 2662-8465. doi:10.1038/s43587-022-00174-3. 
  20. ^ Garcia-Tsao, Guadalupe; Fortune, Brett. Faculty of 1000 evaluation for Systematic review of ophthalmate as a novel biomarker of hepatic glutathione depletion.. 2013-01-30. doi:10.3410/f.717969185.793470080  . 
  21. ^ Ophthalmic acid as a read-out for hepatic glutathione metabolism in humans. Journal of Clinical and Translational Research. 2017. ISSN 2424-810X. PMC 6412618  . doi:10.18053/jctres.03.2017s2.006  . 
  22. ^ 22.0 22.1 Kondoh, Hiroshi; Kameda, Masahiro; Yanagida, Mitsuhiro. Whole Blood Metabolomics in Aging Research. International Journal of Molecular Sciences. 2020-12-26, 22 (1): 175. ISSN 1422-0067. PMC 7796096  . doi:10.3390/ijms22010175  . 
  23. ^ 23.0 23.1 Priolo, Carmen; Khabibullin, Damir; Reznik, Ed; Filippakis, Harilaos; Ogórek, Barbara; Kavanagh, Taylor R.; Nijmeh, Julie; Herbert, Zachary T.; Asara, John M.; Kwiatkowski, David J.; Wu, Chin-Lee; Henske, Elizabeth P. Impairment of gamma-glutamyl transferase 1 activity in the metabolic pathogenesis of chromophobe renal cell carcinoma. Proceedings of the National Academy of Sciences. 2018-06-11, 115 (27). ISSN 0027-8424. PMC 6142242  . doi:10.1073/pnas.1710849115  . 
  24. ^ 24.0 24.1 24.2 Fong, Miranda Y.; McDunn, Jonathan; Kakar, Sham S. Identification of Metabolites in the Normal Ovary and Their Transformation in Primary and Metastatic Ovarian Cancer. PLOS ONE. 2011-05-19, 6 (5): e19963. ISSN 1932-6203. PMC 3098284  . doi:10.1371/journal.pone.0019963  . 
  25. ^ Admin, Ada; Pipino, Caterina; Shah, Hetal; Prudente, Sabrina; Pietro, Natalia Di; Zeng, Lixia; Park, Kyoungmin; Trischitta, Vincenzo; Pennathur, Subramanian. Association of the 1q25 diabetes-specific coronary heart disease locus with alterations of the γ-glutamyl cycle and increased methylglyoxal levels in endothelial cells. 2020-07-10 [2023-11-18]. doi:10.2337/figshare.12616442. 
  26. ^ Kameda, Masahiro; Teruya, Takayuki; Yanagida, Mitsuhiro; Kondoh, Hiroshi. Frailty markers comprise blood metabolites involved in antioxidation, cognition, and mobility. Proceedings of the National Academy of Sciences. 2020-04-15, 117 (17): 9483–9489. ISSN 0027-8424. PMC 7196897  . doi:10.1073/pnas.1920795117  . 
  27. ^ Chaleckis, Romanas; Murakami, Itsuo; Takada, Junko; Kondoh, Hiroshi; Yanagida, Mitsuhiro. Individual variability in human blood metabolites identifies age-related differences. Proceedings of the National Academy of Sciences. 2016-03-28, 113 (16): 4252–4259. ISSN 0027-8424. PMC 4843419  . doi:10.1073/pnas.1603023113  . 
  28. ^ Masood, Afshan; Jacob, Minnie; Gu, Xinyun; Abdel Jabar, Mai; Benabdelkamel, Hicham; Nizami, Imran; Li, Liang; Dasouki, Majed; Abdel Rahman, Anas M. Distinctive metabolic profiles between Cystic Fibrosis mutational subclasses and lung function. Metabolomics. January 2021, 17 (1). ISSN 1573-3882. doi:10.1007/s11306-020-01760-5. 
  29. ^ 29.0 29.1 Sethna, Shirley S.; Gander, John E.; Rathbun, William B. Glutathione synthetase of bovine lens: Anomalies of the enzyme-catalyzed formation of ophthalmic acid. Current Eye Research. January 1984, 3 (7): 923–928. ISSN 0271-3683. doi:10.3109/02713688409167209. 
  30. ^ Waley, S. G. Acidic peptides of the lens. 3. The structure of ophthalmic acid. Biochemical Journal. 1958-01-01, 68 (1): 189–192. ISSN 0306-3283. PMC 1200251  . PMID 13522597. doi:10.1042/bj0680189. 
  31. ^ Schønheyder, F.; Ehlers, N.; Hust, B. Remarks on the Aqueous Humor/Plasma Ratios for Amino Acids and Related Compounds in Patients With Various Chronic Ocular Disorders. Acta Ophthalmologica. September 1975, 53 (4): 627–634. ISSN 1755-375X. doi:10.1111/j.1755-3768.1975.tb01781.x. 
  32. ^ Feuer, Sky K.; Donjacour, Annemarie; Simbulan, Rhodel K.; Lin, Wingka; Liu, Xiaowei; Maltepe, Emin; Rinaudo, Paolo F. Sexually Dimorphic Effect of In Vitro Fertilization (IVF) on Adult Mouse Fat and Liver Metabolomes. Endocrinology. 2014-11-01, 155 (11): 4554–4567. ISSN 0013-7227. PMC 4197990  . doi:10.1210/en.2014-1465  . 
  33. ^ Offord, R E; Philippe, J; Davis, J G; Halban, P A; Berger, M. Inhibition of degradation of insulin by ophthalamic acid and by a bovine pancreatic proteinase inhibitor. Biochemical Journal. 1979-07-15, 182 (1): 249–251. ISSN 0264-6021. PMC 1161257  . PMID 315228. doi:10.1042/bj1820249. 
  34. ^ 34.0 34.1 Soga, Tomoyoshi; Baran, Richard; Suematsu, Makoto; Ueno, Yuki; Ikeda, Satsuki; Sakurakawa, Tadayuki; Kakazu, Yuji; Ishikawa, Takamasa; Robert, Martin; Nishioka, Takaaki; Tomita, Masaru. Differential Metabolomics Reveals Ophthalmic Acid as an Oxidative Stress Biomarker Indicating Hepatic Glutathione Consumption. Journal of Biological Chemistry. June 2006, 281 (24): 16768–16776. ISSN 0021-9258. doi:10.1074/jbc.m601876200  . 
  35. ^ Carretero, Aitor; León, Zacarías; García-Cañaveras, Juan Carlos; Zaragoza, Ángela; Gómez-Lechón, María José; Donato, María Teresa; Lahoz, Agustín. In vitro/in vivo screening of oxidative homeostasis and damage to DNA, protein, and lipids using UPLC/MS-MS. Analytical and Bioanalytical Chemistry. 2014-06-27, 406 (22): 5465–5476. ISSN 1618-2642. doi:10.1007/s00216-014-7983-5. 
  36. ^ Brunelli, Laura; Caiola, Elisa; Marabese, Mirko; Broggini, Massimo; Pastorelli, Roberta. Capturing the metabolomic diversity of KRAS mutants in non-small-cell lung cancer cells. Oncotarget. 2014-05-12, 5 (13): 4722–4731. ISSN 1949-2553. PMC 4148094  . doi:10.18632/oncotarget.1958  . 
  37. ^ Mehta, Hemal H.; Xiao, Jialin; Ramirez, Ricardo; Miller, Brendan; Kim, Su-Jeong; Cohen, Pinchas; Yen, Kelvin. Metabolomic profile of diet-induced obesity mice in response to humanin and small humanin-like peptide 2 treatment. Metabolomics. June 2019, 15 (6). ISSN 1573-3882. PMC 6554247  . doi:10.1007/s11306-019-1549-7  . 
  38. ^ Lee, Jaeyong; Kang, Eun Sil; Kobayashi, Sho; Homma, Takujiro; Sato, Hideyo; Seo, Han Geuk; Fujii, Junichi. The viability of primary hepatocytes is maintained under a low cysteine-glutathione redox state with a marked elevation in ophthalmic acid production. Experimental Cell Research. December 2017, 361 (1): 178–191. ISSN 0014-4827. doi:10.1016/j.yexcr.2017.10.017. 
  39. ^ Goede, Paul; Wüst, Rob C. I.; Schomakers, Bauke V.; Denis, Simone; Vaz, Frédéric M.; Pras‐Raves, Mia L.; Weeghel, Michel; Yi, Chun‐Xia; Kalsbeek, Andries; Houtkooper, Riekelt H. Time‐restricted feeding during the inactive phase abolishes the daily rhythm in mitochondrial respiration in rat skeletal muscle. The FASEB Journal. 2022-01-15, 36 (2). ISSN 0892-6638. doi:10.1096/fj.202100707r  . hdl:20.500.11755/74eab261-4c7d-4293-b7fb-8389b96134d7  . 
  40. ^ 40.0 40.1 Ophthalmic acid as a read-out for hepatic glutathione metabolism in humans. Journal of Clinical and Translational Research. 2017. ISSN 2424-810X. PMC 6412618  . doi:10.18053/jctres.03.2017s2.006  . 
  41. ^ Ghosh, Sujoy; Forney, Laura A.; Wanders, Desiree; Stone, Kirsten P.; Gettys, Thomas W. An integrative analysis of tissue-specific transcriptomic and metabolomic responses to short-term dietary methionine restriction in mice. PLOS ONE. 2017-05-16, 12 (5): e0177513. ISSN 1932-6203. PMC 5433721  . doi:10.1371/journal.pone.0177513  . 
  42. ^ Kaur, Gurnit; Leslie, Elaine M.; Tillman, Holly; Lee, William M.; Swanlund, Diane P.; Karvellas, Constantine J. Detection of Ophthalmic Acid in Serum from Acetaminophen-Induced Acute Liver Failure Patients Is More Frequent in Non-Survivors. PLOS ONE. 2015-09-25, 10 (9): e0139299. ISSN 1932-6203. PMC 4583290  . doi:10.1371/journal.pone.0139299  . 
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