摘要
血管紧张素转化酶在血压调节中具有双重的作用，它将无催化活性的血管紧张素Ⅰ转化为具有活性的血管紧张素Ⅱ，同时，它还可催化降压物质舒缓激肽分解从而导致血压升高。食品蛋白质中存在着活性肽，其中对血管紧张素转化酶具有抑制作用的活性肽(降血压肽)的研究在国内外尤其引人注目，它可通过酶水解食品蛋白质而获得。
采用鸡蛋蛋黄蛋白质为原料，经超临界CO_2-乙醇萃取出蛋黄油和卵磷脂纯化蛋黄蛋白质，得到含量为74.68％的蛋黄蛋白质，蛋白质含量较传统的溶剂提取法提高了24％。经SDS—PAGE法测定，得蛋黄蛋白主要由35kDa、40kDa、67kDa和100kDa以上分子量的蛋白质组成。
用12种蛋白酶酶解蛋黄蛋白质，结果显示所用酶水解产物对ACE皆具有抑制作用；采用体外保温抑制实验将其中活性较好的6种酶解产物进行筛选，确定了产物对ACE的抑制类型，并筛选出酶L为制备蛋黄降血压肽的酶类，其水解产物的IC_(50)为1.19mg／mL。
考察了各因素对酶解的影响，得到蛋黄蛋白质酶解作用最适水解时间为300min、温度为45℃、pH为9.5、底物浓度为60g／L、加酶量为0.42g／kg，此时蛋黄蛋白质水解度为17.2％，氮溶解指数为89.09％，平均肽链长度为6.5。建立了酶解蛋黄蛋白质的水解动力学模型，得到其动力学方程为r=(270.2E_0-0.4125S_0)exp[-0.23(DH)]，动力学模型与实验结果吻合较好。
蛋黄水解液经活性炭脱色、采用截留分子量为10K和3.5K的超滤膜进行分离，所得蛋黄降血压肽超滤液对ACE抑制活性明显提高；用D61大孔阳离子交换树脂对分子量小于3.5kDa的水解液进行分离，确定了离子交换分离降血压肽的适宜条件为：采用pH4.1、浓度为0.05 mol／L的乙酸钠缓冲溶液+1.0mol／L的NaCl溶液，梯度洗脱，上样量为25mg／mL(湿树脂体积)，洗脱速度为0.5mL／min，在此条件下，肽的得率与活性回收率分别为67.2％和73.59％。
用Sephadex G-15对离子交换树脂分离出的穿透峰和洗脱峰分别进行分离和纯化，用RP-HPLC分离纯化最大活性组分峰，用RP-HPLC和高效毛细管电泳(HPCE)进行纯度鉴定，经薄层色谱分析和电喷雾质谱鉴定表征了降血压肽EY-1的结构序列为Leu-Tyr-Pro。
蛋黄水解液的功能研究实验表明，蛋黄水解液有较好的耐热、耐酸稳定性，并发现不同分子量范围的水解产物具有较好的抗油脂氧化性能。与肠道酶作用结果表明，蛋黄水解液与胃蛋白酶作用后其IC_(50)值由1.19mg／mL变为0.94mg／mL，与胰蛋白酶作用后产物的IC_(50)则增至3.19mg／mL，活性有一定的损失，并经毛细管电泳肽谱图得到证实。
Angiotensin-I-converting enzyme (ACE) is by definition associated with therenin-angiotensin system, which regulates peripheral blood pressure. The enzyme canincrease blood pressure by converting angiotensinⅠto the potent vasoconstrictor, angiotensinⅡ, and catalyse the degradation of bradykinin and enkephalins. Inhibition of ACE maytherefore exert an antihypertensive effect and potent synthetic inhibitors of ACE are usedextensively in the treatment of hypertension in humans. A number of ACE-inhibitory peptideshave been isolated and characterised from foods and protein hydrolysates, facilitatingimproved understanding oftheir structure-activity relationship.
As a raw materals, chicken egg yolk was degreased and purified by supercriticalextraction of carbon dioxide and ethanol. The egg yolk protein was obtained in purity of 74.68wt% which was 24 wt% higher than that by traditional method. It was manifested that themain components in the protain were composed of over 35kDa, 40kDa, 67kDa and 100Kdamolecules. The product protein was hydrolyzed by 12 types of protease for preparingantihypertensive peptides following alkaline dephosphorylation, respectively. IC_(50) of thehydrolysates for ACE was determined by high performance liquid chromatographic (HPLC).The stability against ACE for six kinds of hydrolyte which were of lower IC_(50) values amongtwelve were investigated following preincubation. The results showed that 12 types ofhydrolyte had the inhibition effect to ACE. Further more, the preincubation experimentalresults showed that the IC_(50) values of 5 kinds of the hydrolyte had no effect or increaseddespite of preincubation with ACE, and they can be regarded as inhibitor and substrate type.The hydrolyte obtained only from protease L showed that its IC_(50) value (IC_(50)=0.59mg.mL~(-1))against ACE was smaller than that before preincubation (IC_(50)=1.19mg.mL~(-1)) and could be regarded as a prodrug-type ACE inhibitor.
The relation between degree of hydrolysis (DH) of hydrolysate and its inhibition for ACEwas also investigated. The result showed that the optimal technologic conditions forhydrolyzing egg yolks were as following: hydrolysis time was 300 min, hydrolysistemperature 45℃, pH 9.5, the concentrate of substrate (S) 60g/L, and the ratio of enzyme tosubstrate (E/S) 0.42g/kg and then the DH, Nitrogen Solution Index (NSI) and the peptidechain length(PCL) were 17.2wt%, 89.09% and 6.5, respectively. Furthermore, the kineticmodel for the dehydration of egg yolk protein was concluded as:r=(270.2E_0-0.4125S_0)exp[-0.23(DH)], which the experimental results.
The hydrolyte of egg yolk protein was decolored with the active carbon and purified withultrafiitrate membrane which can block the molecules of 10 K and 3.5 K, respectively. Theinhibiting ability of the obtained product to ACE showed an evident increase. The hydrolyteof egg yolk protein with less than 3.5 kDa molecule was adsorbted by a D61 ion exchangeresin. The suitable separation conditions of ion exchange resin adsorption were as following:pH 4.1, the concentration of sodium acetate buffer in 0.05 mol/L plus sodium chloride in1.0mol/L, gradient washing with sampling in 25mg/mL (wet volume), and washing velocityat 0.5mL/min. As results, the yield and activity of the aimed peptide were 63.7% and 73.59%,respectively.
The penetration and desorption sections from ion exchange separation were furtherpurified by Sephadex G-15. The highest active component in the product was enriched andidentfied by RP-HPLC and HPCE. The ACEI sequence was finally testified as Leu-Tyr-Proby thin layer Chromatography and electron spray mass spectrum.
The functional test of egg yolk protein hydrate showed that it was of better heat and acidresistant, and also holds better antioxidant ability in a certain range of molecular weight. Theinteraction result with pepsin would cause its IC_(50) change from 1.19mg/mL to 0.94mg/mL,but that with steapsin would change its IC_(50) from 1.19mg/mL to 3.19mg/mL.
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