组氨酸脱羧酶.doc

组氨酸脱羧酶(HDC)催化作用组胺的形成,生物活性胺。代理控制HDC活动是有益的治疗histamine-mediated症状,如过敏和肠胃溃疡。我们的结果表明,食品包含强大的HDC抑制剂,这些食品有效成分可能是有用的设计临床可用HDC抑制剂。组胺是一种生物活性胺化学介质的过敏反应,神经递质,和胃酸分泌的诱导物(Shahid Khardori,汗,和非洲2011)。组氨酸脱羧酶(HDC。4.1.1.22)是唯一的酶参与了哺乳动物的组胺合成。抑制体内HDC活动降低组胺水平;因此,抑制HDC的代理活动将是有用的治疗histamine-mediated症状,如过敏、胃肠溃疡和炎症。然而,尽管收到重视,寻找HDC抑制剂没有足够成功,可能是因为困难处理酶和HDC的少量研究组织由于组胺释放是在许多炎症反应的主要活动之一,一个新的潜在的应用(-)-epigallocatechin-3-gallate在预防或治疗炎症 (Nitta et al., 2007 and Rodriguez-Caso et al., 2003)Histidine decarboxylase (HDC) catalyzes histamine formation from histidine. Histamine is a bioactive amine acting as a neurotransmitter as well as a chemical mediator. Phenolic food components have been tested for their ability to inhibit recombinant human HDC. Epicatechin gallate (ECG) was found to be a potent inhibitor as it inhibited HDC activity in a competitive manner with Ki = 10 M against L-histidine. Epigallocatechin gallate (EGCG) showed time-dependent inhibition which disappeared under anaerobic conditions. It is probable that time-dependent inhibition could be due to the result of autoxidation of EGCG. The initial burst observed for EGCG suggests that EGCG itself is involved in HDC inhibition as observed for ECG. Our present results have shown that the tested food components can inhibit HDC activity. This inhibition likely affects histamine biosynthesis and possibly leads t组氨酸脱羧酶(HDC)催化组氨酸的组胺的形成。组胺是一种生物活性胺作为一种神经递质以及化学介质。酚醛食品组件测试的能力抑制人类HDC重组。表儿茶素没食子酸盐(ECG)被发现是一个强有力的抑制剂,抑制HDC活动竞争的方式与Ki = 10M组氨酸。儿茶素没食子酸盐(EGCG)显示时间抑制而在厌氧条件下就会消失。时间很可能是抑制可能是由于EGCG的自氧化的结果。EGCG的初始破裂观察表明,EGCG本身参与HDC抑制作为心电图观察。我们目前的结果表明,测试食品成分可以抑制HDC活动。这种抑制作用可能影响组胺生物合成并可能导致tAbstract Histamine, a bioactive amine, is formed from histidine through histidine decarboxylase (HDC). The agent that controls histamine synthesis, i.e. activity of HDC, is beneficial for controlling histamine-related physiological actions, such as inflammation. In the present study, the ethyl acetate (EtOAc) extract of the berries of Pimenta dioica was investigated for its potency as an HDC inhibitor. Two quercetin glycosides from P. dioica, quercetin 3-O-d-glucuronide 6 -methyl ester and quercetin 3-O-(2-O-galloyl)glucoside were identified as potent HDC inhibitors (64% and 55% inhibition at 1 mM, respectively). The inhibitory rates of these quercetin glycosides were nearly comparable to that of epigallocatechin gallate, another HDC inhibitor (75% at 1 mM). The approach to seek active components from natural products is useful for obtaining HDC inhibitors.抽象的组胺,通过组氨酸生物活性胺,是由组氨酸脱羧酶(HDC)。代理控制组胺合成,即HDC的活动,有利于控制histamine-related生理行为,如炎症。在目前的研究中,乙酸乙酯(层)提取的浆果Pimenta dioica追究其效力HDC抑制剂。两个从p . dioica槲皮素苷,槲皮素3-O-d-glucuronide 6 -methyl酯和槲皮素3-O -葡萄糖苷(2-O-galloyl)被确定为有效的HDC抑制剂(分别为64%和55%抑制在1毫米)。槲皮素苷的抑制率几乎与儿茶素的另一个HDC抑制剂在1毫米(75%)。寻求从天然产物活性成分的方法是用于获取HDC抑制剂。Alkaloids inhibiting l-histidine decarboxylase from Sinomenium acutumHDC has been shown to have greatly reduced activity at neutral or alkaline pH. This is largely a substrate binding effect in that the enzyme has a Km of 0.3 mM at pH 4.8 and 100 mM at pH 7 15. The X-ray model at pH 4.8 5 and 6 represents the active form of HDC; here we present the structure of the less active form of HDC at pH 8 (HDC-8).Histamine is the causative agent of scombroid poisoning, a food-borne chemical hazard. Scombroid poisoning is usually a mild illness with a variety of symptoms, including rash, urticaria, nausea, vomiting, diarrhea, flushing, and tingling and itching of the skin (Taylor, 1986). Severity of the symptoms can vary considerably with the amount of histamine ingested and the individual s sensitivity to histamine (Russell & Maretic, 1986). Scombroid fish, such as tuna, mackerel, bonito, and saury, that contain high levels of free histidine in their muscle, are often implicated in scombroid poisoning incidents (Taylor, 1986). However, several species of nonscombroid fish, such as mahi-mahi, bluefish, herring and sardine, have often been implicated in incidents of scombroid poisoning组胺是鲜鱼的病原体中毒,食物的化学危害。鲜鱼中毒通常是一个温和的疾病与各种各样的症状,包括皮疹、荨麻疹、恶心、呕吐、腹泻、冲洗、刺痛和痒的皮肤(泰勒,1986)。症状的严重程度相差很大的组胺摄取和各个年代对组胺(Russell & Maretic,1986)。鲜鱼的鱼,如金枪鱼、鲭鱼、鲣鱼、秋刀鱼,含有高水平的免费组氨酸的肌肉,往往涉及鲜鱼中毒事件(泰勒,1986)。然而,数种nonscombroid鱼类,如mahi-mahi、竹荚鱼的时候,鲱鱼和沙丁鱼,经常涉及鲜鱼中毒的事件虱目鱼(查诺斯查诺斯)是一个重要的aquacultured鱼的印度洋地区,尤其是菲律宾、印尼和台湾(陈,1990)。组氨酸,约441毫克/ 100克,是最著名的游离氨基酸(FAA)中发现的白色肌肉虱目鱼,占总数的80%法斯的鱼(- 12、Shiau &柴,1990)。虱目鱼有FAA模式类似于洄游鱼类,如鲭鱼、金枪鱼和箭鱼,也拥有非常高水平的组氨酸在白色肌肉(Konosu山口,1982和铃木et al .,1987)。蔡,最近,龚,魏,和黄(2005)报道,虱目鱼基质比是旗鱼组胺形成的细菌组氨酸脱羧在高温( 15 C)。然而,不像鲭鱼、金枪鱼、箭鱼、旗鱼组胺中毒,由于消费的牛奶组织胺(Histamine)是一种活性胺化合物，化学式是C5H9N3，分子量是111。作为身体内的一种化学传导物质，可以影响许多细胞的反应，包括过敏，发炎反应，胃酸分泌等，也可以影响脑部神经传导，会造成想睡觉等效果。 组织胺存在于肥满细胞内，亦存在于肺、肝及胃的粘膜组织内。它在过敏与发炎的调节上扮演一个很重要角色。组织胺属于一种化学讯息，亦是aminergic neurotransmitter，参与中枢与周边的多重生理功能。在中枢系统，组织胺是由特定的神经所合成例如位在posterior hypothalamus 的tuberomammillary nucleus，神经细胞多向延伸至大脑其他区域与脊椎，因此暗示组织胺可能参与睡眠，荷尔蒙的分泌，体温调节，食欲与记忆形成等功能，另外还位于formatio reticularis与telencephan；在周边部分，组织胺主要储存在mast cell, basophils 和enterochromaffin cells，可引起痒、打喷嚏、流鼻水等现象，此外组织胺结合到血管平滑肌上的接受器(H1R)导致血管扩张因而产生局部水肿，组织胺会使肺的气管平滑肌收缩引起呼吸道狭窄进而呼吸困难，肠道平滑肌收缩降低血压以及增加心跳(tachycardia)等多项生理反应。 中国生物制品学杂志2010年11月第23卷第11期ChinJBiologicalsNovember2010，Vol.23No.11组胺（Histamine，HA）是由组氨酸脱羧酶（Histidinedecarboxylase，HDC）催化L-组氨酸脱羧生成的一种重要生理活性介质。适量的生物胺在人和动物活性细胞中发挥着重要的生理作用，但在人体内积累量较高时，会产生毒性作用1。食品中组胺最大允许水平为50100mgkg2。由于发酵食品中的组胺多由微生物通过分泌脱羧酶而生成，因此，控制原料中的微生物生长和抑制发酵剂中生物胺的形成对发酵食品的安全性至关重要。组胺（Histamine，HA）是由组氨酸脱羧酶（Histidinedecarboxylase，HDC）催化L-组氨酸脱羧生成的一种重要生理活性介质。适量的生物胺在人和动物活性细胞中发挥着重要的生理作用，但在人体内积累量较高时，会产生毒性作用1。食品中组胺最大允许水平为50100mgkg2。由于发酵食品中的组胺多由微生物通过分泌脱羧酶而生成，因此，控制原料中的微生物生长和抑制发酵剂中生物胺的形成对发酵食品的安全性至关重要。目前，乳酸菌为发酵食品加工中常用的微生物发酵剂3，主要有：乳杆菌属、乳球菌属、肠球菌属、明串珠菌属等。国外研究者正在对产组胺的微生物发酵剂进行分子生物学方面的研究，从而控制组胺的形成，但尚无突破性进展。Lactobacillussakei、Te-tragenococcus