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酪啡肽(β-Casomorphin)的定义
β-酪啡肽是由β-酪蛋白消化产生的肽，长度为 4-11 个氨基酸【1】。 它们表现出阿片类药物或吗啡样功能【1】。
Beta-Casomorphins are peptides resulting from the digestion of beta-Casein and vary from 4-11 amino acids in length【1】. They exhibit opioid or morphine-like functions【1】.
酪啡肽(β-Casomorphin)的发现
β-酪啡肽首先从豚鼠回肠的酪蛋白消化物中纯化，基于其显示阿片类活性的能力【2】。
ß-Casomorphins were first purified from casein digest of guinea pig ileum based on their ability to show opioid activity【2】.
酪啡肽(β-Casomorphin)的分类
ß-酪啡肽是阿片肽【1】。已鉴定出几种天然存在的β-酪啡肽 (BCM)：牛 BCM-4、牛 BCM-5、牛 BCM-6、牛 BCM-7、牛 BCM-8、牛 BCM-11、人 BCM-7、人 BCM-8 。 已经合成了几种类似物，它们是天然存在的 BCM 的结构修饰变体【1】。
ß-Casomorphins are opioid peptides【1】. Several naturally occurring ß-Casomorphins (BCM) have been identified: Bovine BCM-4, Bovine BCM-5, Bovine BCM-6, Bovine BCM-7, Bovine BCM-8, Bovine BCM-11, Human BCM-7, Human BCM-81. Several analogues which are structurally modified variants of naturally occurring BCMs have been synthesized【1】.
酪啡肽(β-Casomorphin)的结构特点
BCM 的长度为 4-11 个氨基酸。天然存在的 BCM 的序列如下1所示：
牛 BCM-4 Tyr-Pro-Phe-Pro
牛 BCM-5 Tyr-Pro-Phe-Pro-Gly
牛 BCM-6 Tyr-Pro-Phe-Pro-Gly-Pro
牛 BCM-7 Tyr-Pro-Phe-Pro-Gly-Pro-Ile
牛 BCM-8 Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro
牛 BCM-11 Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-Asn-Ser-Leu
人 BCM-7 Tyr-Pro-Phe-Val-Glu-Pro-Ile
人 BCM-8 Tyr-Pro-Phe-Val-Glu-Pro-Ile-Pro
BCM类似物的一些序列如下所示：
H-Tyr-Pro-Phe-Pro-Gly-EtDA-Gly-II
H-Tyr-Pro-Phe-Pro-Gly-EtDA-Gly-Gly-II
H-Tyr-Pro-Phe-Pro-Gly-EtDA-Gly-Gly-CO-CH3
H-Tyr-Pro-Phe-Pro-Gly-EtDA-Gly-Gly-CO-CH2-CH2-COOH
酪啡肽(β-Casomorphin)的作用方式
关于 BCM 功能的确切机制目前还没有太多研究。众所周知，它们通过与细胞膜上的阿片受体结合来发挥阿片功能【4】。 最近的研究表明，BCM-7 是大脑中血管紧张素受体的高亲和力配体【4】。
Not much has been studies on the exact mechanism of BCM function. It is known that they exert their opioid functions by binding to opioid receptors on cell membranes【4】. Recent studies have shown that BCM-7 is a high affinity ligand for angiotensin receptor in the brain【4】.
酪啡肽(β-Casomorphin)的功能
BCM 对胃肠道产生影响。 例如，它们通过刺激胰岛素和生长抑素的分泌来影响餐后代谢，并调节肠道中氨基酸的转移【5】。 影响缺氧，因为已经表明，当给怀孕大鼠施用 BCM7 时，可以诱导其从缺氧状态中恢复。 BCM-5 和类似物参与大鼠旋转行为的产生【4】。 BCM-8 参与哺乳期间母亲和孩子之间的相互作用【7】。 最后，BCM 与多种疾病有关，包括 SIDS 和儿童自闭症【1】。
BCMs produce effects in the gastrointestinal tract. For instance they influence post prandial metabolism by stimulating the secretion of insulin and somatostatin and modulate transfer of amino acids in the intestine【5】. The affect hypoxia as it has been shown that BCM7 when administered to pregnant rats induces their recovery from hypoxic condition【4】. BCM-5 and analogs are involved in producing rotational behavior in rats6. BCM-8 is involved in interplay between mother and child during lactation【7】. Finally, BCMs have been implicated in several diseases including SIDS and childhood autism【1】.
酪啡肽(β-Casomorphin)的相关文献
1、Kamiñski S, Cieoeliñska A, Kostyra E (2007). Polymorphism of bovine beta-casein and its potential effect on human health. J Appl Genet, 48(3), 189–198.
2、Ramabadran K, Bansinath M (1989). Pharmacology of beta-casomorphins, opioid peptides derived from milk protein. Asia Pac J Pharmacol, 4, 45–58.
3、Sobirov MM, Khalikov ShKh, Saidov SS, Kodirov MZ, Zaitsev SV, Chichenkov ON, Varfolomeev SD (1994). Synthesis and biological activity of new analogs of beta-casomorphine-5. Bioorg Khim., 20(7), 740-50.
4、Book: Handbook of Biologically Active Peptides by Abba J. Kastin.
5、Zoghbi S, Trompette A, Claustre J, Homsi ME, Garzo´n J, Jourdan G, Scoazec JY and Plaisancie P (2006). Casomorphin-7 regulates the secretion and expression of gastrointestinal mucins through a opioid pathway. Am J Physiol Gastrointest Liver Physiol 290, G1105–G1113.
6、Marschitz HM, Terenius L, Grehn L, Ungerstedt U (1989). Rotational behaviour produced by intranigral injections of bovine and human beta-casomorphins in rats. Psychopharmacology (Berl), 99(3), 357-61.
7、Ivano DN, Richard JF, Hannu JTK, Yves LR, Chris TL, Inga T, Daniel T, Renger W, (2009). Review of the potential health impact of ß-casomorphins and related peptides. EFSA Scientific Report, 231, 1-107.
