跳至內容

眼晶體酸

維基百科，自由的百科全書
眼晶體酸
IUPAC名
(N-(L-γ-Glutamyl)-(2S)-2-aminobutyryl)glycine
別名 視晶酸
識別
CAS號 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
性質
化學式 C11H19N3O6
摩爾質量 289.29 g·mol−1
外觀 白色晶體
若非註明，所有數據均出自標準狀態（25 ℃，100 kPa）下。

眼晶體酸[1]或視晶酸（英語：Ophthalmic acid，ophthalmate，縮寫OPH）是一種三肽，從化學結構上可稱為L-γ-穀氨醯-L-α-氨基丁醯基甘氨酸。其為穀胱甘肽的類似物，與穀胱甘肽的區別在於將結構中半胱氨酸替換成了L-2-氨基丁酸。L-2-氨基丁酸是一種非蛋白質胺基酸，其沒有半胱氨酸所具備的親核性巰基，同時巰基也是穀胱甘肽各種重要功能的來源基團，因此眼晶體酸曾一度被錯誤地視為生物合成穀胱甘肽過程中產生的錯誤副產物。

2024年，Schomakers等人根據已有研究，提出了眼晶體酸是穀胱甘肽的一種調節因子的假設。其認為眼晶體酸作為穀胱甘肽調節三肽，影響細胞和細胞器穀胱甘肽的流入和流出，並調節與穀胱甘肽有關的反應和信號傳導[2]。

生物合成

眼晶體酸由2-氨基丁酸作為原料合成，其涉及的酶和生產穀胱甘肽的酶一樣，都是穀氨酸-半胱氨酸連接酶（英語：Glutamate–cysteine ligase）和穀胱甘肽合成酶（英語：Glutathione synthetase）。影響眼晶體酸生物合成的主要因素是半胱氨酸和2-氨基丁酸的局部相對濃度，以及它們的γ-穀氨醯中間產物[2]。

發現與分布

眼晶體酸最早於1956年在牛犢的晶狀體中發現[3]。此後發現其是一種在普遍存在的代謝物。各種生物體中都發現了眼晶體酸，包括：

在高度動物體內各種器官組織中也廣泛分布：包括大腦[16] 、眼[16] 、肝[16][14]、腎臟[14]、心臟[17]、生殖腺[32]、卵巢[24] 、肌肉[19]、脂肪組織[33]、血液[22]、血漿[34]、紅血球[15]以及糞便[9]。

在植物中，其存在於種子[7]、葉片[7]、果肉[8]、豆莢[9]等部位。

氧化應激標誌爭論

在2006年一項在小鼠施加過量對乙醯氨基酚的代謝學研究中，眼晶體酸經常別視為一種氧化應激標誌物，將其濃度改變行為與受到氧化應激聯繫起來[34]。然而不同學者對其持有不同意見：

即使觀測到了兩者之間的相對變化[7][35]，但不意味著眼晶體酸增加與穀胱甘肽減少之間沒有相關性。相對於健康標準值，兩者可同增[13][23]同減[36][37]，或者眼晶體酸單獨增加[24][38][11]。一項眼晶體酸與穀胱甘肽的晝夜節律追蹤實驗顯示：眼晶體酸濃度有晝夜節律然而穀胱甘肽沒有[39]。在同一時間，同一動物的不同組織之間眼晶體酸水平變化趨勢的也有很大差異[40][41]。這些研究結果均表明眼晶體酸與穀胱甘肽之間沒有相關性。

而且也有研究發現眼晶體酸在正常的組織中含量也很高，比如眼睛中，意味著其不僅僅存在於受到應激和疾病的組織中[29]。

後續也有研究推翻了2006年的小鼠實驗，證實其研究方法不可靠[42][40]。

參考文獻

  1. ^ 蘇子仁，賴小平 (編). 汉英、英汉中草药化学成分词汇. 北京: 中國中醫藥出版社. 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 可免費查閱. （原始內容存檔於2024-03-10） （英語）. 
  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 可免費查閱. 
  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 可免費查閱. doi:10.3390/nu11010028 可免費查閱. 
  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 可免費查閱. doi:10.1016/j.xpro.2022.101302 可免費查閱. 
  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 可免費查閱. doi:10.1073/pnas.2003650117 可免費查閱. 
  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 可免費查閱. doi:10.1371/journal.pone.0175491 可免費查閱. 
  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 可免費查閱. doi:10.1371/journal.pone.0153750 可免費查閱. 
  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 可免費查閱. 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 可免費查閱. doi:10.1155/2011/789323 可免費查閱. 
  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 可免費查閱. 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 可免費查閱. 
  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 可免費查閱. doi:10.18053/jctres.03.2017s2.006 可免費查閱. 
  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 可免費查閱. doi:10.3390/ijms22010175 可免費查閱. 
  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 可免費查閱. doi:10.1073/pnas.1710849115 可免費查閱. 
  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 可免費查閱. doi:10.1371/journal.pone.0019963 可免費查閱. 
  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 可免費查閱. doi:10.1073/pnas.1920795117 可免費查閱. 
  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 可免費查閱. doi:10.1073/pnas.1603023113 可免費查閱. 
  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 可免費查閱. 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 可免費查閱. doi:10.1210/en.2014-1465 可免費查閱. 
  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 可免費查閱. 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 可免費查閱. 
  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 可免費查閱. doi:10.18632/oncotarget.1958 可免費查閱. 
  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 可免費查閱. doi:10.1007/s11306-019-1549-7 可免費查閱. 
  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 可免費查閱. hdl:20.500.11755/74eab261-4c7d-4293-b7fb-8389b96134d7 可免費查閱. 
  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 可免費查閱. doi:10.18053/jctres.03.2017s2.006 可免費查閱. 
  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 可免費查閱. doi:10.1371/journal.pone.0177513 可免費查閱. 
  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 可免費查閱. doi:10.1371/journal.pone.0139299 可免費查閱. 
取自「https://zh.wikipedia.org/w/index.php?title=眼晶体酸&oldid=84496827」