眼晶體酸

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
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-穀氨酰-L-α-氨基丁酰基甘氨酸。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氨基酸，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。

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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-穀氨酰中間產物^[2]。

發現與分佈

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：

各種細菌^[4]^[5]
各種真菌^[6]
各類無情緣關係的植物^[7]^[8]^[9]
各種線蟲^[10]，如秀麗隱杆線蟲
各種昆蟲^[11]
各種有脊椎動物：魚類^[12]；鳥類^[13]；齧齒動物^[14]^[15]^[16]^[17] 、兔子^[16]以及人類^[9]^[18]^[19]^[20]^[21]^[22]^[23]^[24]^[25]^[26]^[27]^[28]等哺乳動物^[29]^[30]^[16]^[31]。

在高度動物體內各種器官組織中也廣泛分佈：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]、紅細胞^[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酰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]，但不意味着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，意味着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

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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.
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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 . （原始內容存檔於2024-03-10）（英語）.
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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.
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[1] [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.

[:14-2] [2]
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 . （原始內容存檔於2024-03-10）（英語）.

[3] [3]
Waley SG; Biochem. J. 64, 715 (1956)

[4] [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] [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] [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.

[:0-7] [7]
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.

[:1-8] [8]
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.

[:2-9] [9]
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] [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 .

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