唐志如 宋代軍 董國(guó)忠 孫志洪 李周權(quán)

(西南大學(xué)動(dòng)物科技學(xué)院,重慶 400716)

母豬營(yíng)養(yǎng)生理狀況直接影響胎兒及新生仔豬的生長(zhǎng)和健康?；蚋牧己蟮默F(xiàn)代母豬具有更高的繁殖力,其后代擁有更高的生長(zhǎng)潛力。然而,目前妊娠母豬的限飼方案限制了胎兒生長(zhǎng)所需營(yíng)養(yǎng)素的攝取,尤其是妊娠中期和后期的限飼。哺乳期間降低母豬采食量的飼養(yǎng)方式減少了乳中營(yíng)養(yǎng)物質(zhì)的供給,進(jìn)而導(dǎo)致大量母體組織中營(yíng)養(yǎng)物質(zhì)的動(dòng)員[1]。母體分解代謝狀況會(huì)限制胎兒及新生仔豬的生長(zhǎng),增加發(fā)病率及死亡率,其潛在的機(jī)理與胎兒及新生仔豬功能性氨基酸攝取量減少有關(guān)。功能性氨基酸不僅為動(dòng)物正常生長(zhǎng)及維持代謝所必需,而且是合成許多生物活性物質(zhì)的必需前體物質(zhì)[2]。具有特殊功能的氨基酸包括精氨酸、支鏈氨基酸、谷氨酸、色氨酸和脯氨酸。這些功能性氨基酸有利于處于分解代謝狀態(tài)的妊娠母豬胎兒的生長(zhǎng)、新生仔豬的健康及哺乳期母豬生產(chǎn)性能的發(fā)揮。

1 功能性氨基酸概述

由于支鏈的變化,氨基酸的生物學(xué)特性和功能也具有多樣性。妊娠期羊水[3]、1周齡新生仔豬血漿[4]及處于分解代謝狀態(tài)下的所有動(dòng)物血漿[5]中氨基酸濃度是變化的。母豬乳(哺乳第28天濃度為3.5 mmol/L)[6]、血漿 (0.5 ～1 mmol/L)[7]、骨胳肌(5～20 mmol/L)[8]、妊娠早期羊水(2～3 mmol/L)[9]及尿囊液(3 ～25 mmol/L)[3]中谷氨酸含量特別豐富。精氨酸及瓜氨酸(精氨酸前體)含量在妊娠早期豬及羊的尿囊液中特別豐富,分別為4 ～6 mmol/L和5 ～10 mmol/L[3,9]。

一直以來(lái),必需氨基酸在動(dòng)物營(yíng)養(yǎng)中的作用倍受關(guān)注[10]。近年來(lái),由于非必需氨基酸及必需氨基酸在代謝調(diào)控及生理上獨(dú)特的多樣化功能,人們對(duì)它們產(chǎn)生了更大的興趣。那些碳骨架不能為動(dòng)物所合成或者能合成但不能滿足動(dòng)物需要,必需通過(guò)飼糧供給才能滿足其維持、生長(zhǎng)和繁殖需要的氨基酸被定義為必需氨基酸[2]。必需氨基酸在正常情況下動(dòng)物體內(nèi)能充足合成,但在利用率相對(duì)于合成率增加的情況下,必需通過(guò)飼糧供給才能滿足需要[2]。非必需氨基酸是指那些動(dòng)物體內(nèi)能足夠合成以滿足需要的氨基酸[2]。動(dòng)物在成千上萬(wàn)年進(jìn)化過(guò)程中保存了合成為生存及繁殖所必需的氨基酸能力。

自然界中有300種以上的氨基酸,但只有20種參與動(dòng)物細(xì)胞蛋白質(zhì)的構(gòu)成(表1)。近年來(lái),有研究表明,一些氨基酸能調(diào)節(jié)細(xì)胞內(nèi)蛋白質(zhì)合成與降解,參與許多為生命及繁殖所必需生物活性物質(zhì)(一氧化氮、多胺、谷胱甘肽、核酸、激素和神經(jīng)遞質(zhì))的合成。

表1 動(dòng)物營(yíng)養(yǎng)性必需氨基酸與非必需氨基酸Table 1 Nutritionally essential and nonessential amino acids in animals

2 功能性氨基酸的生物學(xué)作用

2.1 功能性氨基酸對(duì)細(xì)胞內(nèi)蛋白質(zhì)周轉(zhuǎn)的作用

2.1.1 亮氨酸

細(xì)胞內(nèi)蛋白質(zhì)不斷地合成與分解稱為蛋白質(zhì)周轉(zhuǎn),其被用來(lái)測(cè)定細(xì)胞內(nèi)蛋白質(zhì)平衡及細(xì)胞或組織氨基酸凈損失。20年前,亮氨酸被發(fā)現(xiàn)能刺激在分解代謝狀態(tài)下培養(yǎng)的骨骼肌蛋白質(zhì)合成,同時(shí)抑制其蛋白質(zhì)的降解[11]。體內(nèi)研究進(jìn)一步確定,通過(guò)口服亮氨酸或飼糧中添加亮氨酸來(lái)提高血漿中亮氨酸水平的方法能加速處于生理狀態(tài)下的新生仔豬蛋白質(zhì)的合成[12-13]。通過(guò)分子技術(shù)更深入的研究發(fā)現(xiàn),亮氨酸是通過(guò)刺激哺乳動(dòng)物雷帕霉素(rapamycin)靶信號(hào)(mTOR)加速肌肉蛋白質(zhì)合成的。mTOR磷酸化對(duì)亮氨酸水平升高的反應(yīng)導(dǎo)致p70S6激酶(p70S6K)和真核起始因子4E結(jié)合蛋白1(4E-BP1)的磷酸化,而4E-BP1能促進(jìn)多肽合成起始復(fù)合體[14]。亮氨酸抑制肌肉蛋白質(zhì)降解的機(jī)理是亮氨酸氨基轉(zhuǎn)移產(chǎn)生 α-酮異己酸[11]。另有研究表明,肝臟灌注亮氨酸減緩肝臟蛋白質(zhì)降解,原因可能是通過(guò)mTOR介導(dǎo),抑制自由噬菌體的生長(zhǎng),其主要機(jī)理是蛋白質(zhì)進(jìn)入溶酶體引起水解[14]。亮氨酸也能激活腸上皮細(xì)胞mTOR信號(hào)途徑[15]。

2.1.2 谷氨酸

在各種分解代謝情況下(受傷、化膿和哺乳),肌肉內(nèi)谷氨酸水平顯著下降,這與骨骼肌中蛋白質(zhì)負(fù)平衡有關(guān)[16],這提示氨基酸與蛋白質(zhì)周轉(zhuǎn)可能存在關(guān)聯(lián)。骨骼肌中注射谷氨酸鹽可加速蛋白質(zhì)合成并抑制蛋白質(zhì)分解[17]。近年來(lái)體內(nèi)研究進(jìn)一步證明,仔豬肌肉內(nèi)谷氨酸濃度和肌肉蛋白質(zhì)合成存在正相關(guān)關(guān)系[18-19]。谷氨酸還能刺激小腸黏膜蛋白質(zhì)合成并抑制蛋白質(zhì)水解[20]。谷氨酸在心肌細(xì)胞[21]和Jurkat細(xì)胞[22]中生理功能的作用機(jī)理還不清楚,但也可能與mTOR信號(hào)物質(zhì)有關(guān)。mTOR信號(hào)途徑的激活可能是在飼糧中添加L-谷氨酸可抑制早期斷奶仔豬小腸萎縮征的部分原因[23]。由于亮氨酸、異亮氨酸和纈氨酸是動(dòng)物組織(特別是骨骼肌)中合成谷氨酸的物質(zhì)[1],而谷氨酸又具有部分介導(dǎo)動(dòng)物支鏈氨基酸分解代謝的作用。所以,這種作用使得乳腺產(chǎn)生的谷氨酸比從血液循環(huán)中獲得的谷氨酸要多[24],且胎盤能合成并釋放大量的谷氨酸進(jìn)入胎兒血液循環(huán)[25],這對(duì)增加哺乳期乳腺及胎盤中谷氨酸的含量具有重要意義。

2.1.3 精氨酸

有研究表明,精氨酸能加速處于分解狀況下(感染、營(yíng)養(yǎng)失調(diào))豬小腸蛋白質(zhì)的合成[26]。然而,培養(yǎng)基中精氨酸的添加對(duì)哺乳動(dòng)物的肝細(xì)胞mTOR的磷酸化沒(méi)有影響[14]。這些發(fā)現(xiàn)可由以下事實(shí)得以解釋:由于肝細(xì)胞中具有高活性的精氨酸酶加速其分解,因此,肝細(xì)胞中精氨酸濃度極低(小于50 μmol/L)[27]。然而,新生仔豬腸道上皮細(xì)胞中精氨酸酶活力較低,這樣,細(xì)胞外精氨酸(腸魯米諾精氨酸)濃度上升可有效地增加細(xì)胞內(nèi)精氨酸濃度[28]。另有報(bào)道,精氨酸能激活mTOR和其他腸上皮細(xì)胞內(nèi)起介導(dǎo)信號(hào)作用的激酶[15],從而刺激蛋白質(zhì)合成,促進(jìn)損傷的腸上皮的修復(fù)。這為精氨酸利于新生仔豬腸道的完整性和腸道功能的發(fā)揮提供了一個(gè)研究機(jī)理[29]。近年來(lái)的研究還發(fā)現(xiàn),通過(guò)飼糧供給精氨酸[30]或內(nèi)源性精氨酸的合成代謝活化作用[31],可提高哺乳仔豬血漿中精氨酸水平,進(jìn)而提高骨骼肌和全身肌肉蛋白質(zhì)合成。這些合成代謝的影響與增加肌肉蛋白質(zhì)合成相關(guān)[32]。肌肉蛋白質(zhì)合成程度高于蛋白質(zhì)降解的事實(shí)提示精氨酸可能還具有調(diào)控新生仔豬肌肉蛋白質(zhì)降解的作用[32]。

2.2 功能性氨基酸對(duì)胎兒生長(zhǎng)的作用

亮氨酸、谷氨酸和精氨酸對(duì)妊娠期胚胎、胎盤和胎兒發(fā)育具有重要作用[33-34]。豬和綿羊妊娠前3個(gè)月羊水及尿囊液中谷氨酸和精氨酸濃度增加25～80倍,這個(gè)階段對(duì)胎盤的生長(zhǎng)發(fā)育很關(guān)鍵[3]。另外,妊娠的第11天到第15天,羊子宮液這2種氨基酸和亮氨酸的濃度增加10～50倍[35]。這些在特定時(shí)期異常豐富的氨基酸通過(guò)細(xì)胞內(nèi)蛋白質(zhì)周轉(zhuǎn)及細(xì)胞增殖調(diào)控,在胚胎形成、著床,胎盤生長(zhǎng)、發(fā)育和胎兒生長(zhǎng)過(guò)程中起到關(guān)鍵作用[36]。在妊娠第30天到分娩期間母豬飼糧中添加1.0%L-精氨酸,活仔數(shù)量提高23%,總產(chǎn)仔窩重增加28%[37]。這個(gè)報(bào)道首次發(fā)現(xiàn)了通過(guò)營(yíng)養(yǎng)干預(yù)每頭母豬產(chǎn)仔數(shù)量的增加大于2頭。

2.3 功能性氨基酸對(duì)激素分泌和代謝的調(diào)控作用

許多多肽和低分子量激素是由特定氨基酸合成的(表2)。例如,酪氨酸是合成腎上腺素、去甲腎上腺素和甲狀腺素的前體。氨基酸也是內(nèi)分泌細(xì)胞分泌激素的有效調(diào)控者[38]。精氨酸能刺激胰島素、生長(zhǎng)激素、泌乳激素、胰高血糖素和胎盤催乳激素的分泌[39]。谷氨酸和亮氨酸能增加胰腺β-細(xì)胞胰島素的分泌[38]。飼糧中添加谷氨酸能通過(guò)一種未知的機(jī)理減少斷奶仔豬糖皮質(zhì)激素的產(chǎn)生[40]。這些氨基酸可以部分地介導(dǎo)飼糧蛋白質(zhì)對(duì)機(jī)體蛋白質(zhì)、脂肪和葡萄糖代謝及動(dòng)物生產(chǎn)性能和動(dòng)物產(chǎn)品品質(zhì)的影響。

除了影響血漿激素水平外,氨基酸直接參與中間代謝調(diào)控和飼糧營(yíng)養(yǎng)素的利用:1)精氨酸是N-乙酰谷氨酸酯合成酶(一種用谷氨酸和乙酰輔酶A作為底物線粒體酶)變構(gòu)增活因子[27]。精氨酸和谷氨酸能促進(jìn)機(jī)體的尿素循環(huán)。2)丙氨酸抑制丙酮酸激酶,進(jìn)而調(diào)控糖的合成和糖酵解,以保證在采食食物時(shí)肝細(xì)胞的凈糖產(chǎn)生量[2]。3)谷氨酸和天冬氨酸可減少與糖酵解相關(guān)物質(zhì)的線粒體跨膜轉(zhuǎn)化作用,進(jìn)而調(diào)節(jié)糖酵解和細(xì)胞氧化還原狀態(tài)[41]。4)精氨酸和苯丙氨酸調(diào)節(jié)三磷酸鳥(niǎo)苷環(huán)水解酶I表達(dá)和活性,進(jìn)而增強(qiáng)四氫生物蝶呤對(duì)精氨酸-環(huán)烷油合成作用和對(duì)芳香氨基酸羥基化作用的有效性[42]。精氨酸-環(huán)烷油途徑也可以通過(guò)許多其他氨基酸(賴氨酸、谷氨酸、巰基丁氨酸)調(diào)控來(lái)發(fā)揮它們的生理作用[43]。5)精氨酸和它的代謝物調(diào)節(jié)有關(guān)線粒體生物合成和底物氧化作用關(guān)鍵蛋白質(zhì)和酶(腺苷-磷酸激活的蛋白激酶、過(guò)氧化物酶體增殖因子活化受體-γ和活化劑-α)的表達(dá),進(jìn)而減少肥胖動(dòng)物脂肪含量[44-45]。6)蛋氨酸、甘氨酸和絲氨酸在一碳代謝過(guò)程中起到重要作用,利于蛋白質(zhì)和DNA甲基化,進(jìn)而調(diào)節(jié)基因表達(dá)和蛋白活性[46]。另外,氨基酸代謝在肝、骨骼肌、小腸和免疫細(xì)胞中的調(diào)節(jié)作用使谷氨酸最大程度轉(zhuǎn)化為腎氨水,因此,氨基酸可調(diào)節(jié)動(dòng)物體內(nèi)的酸堿平衡[16]。

表2 氨基酸在動(dòng)物體內(nèi)代謝所產(chǎn)生的重要含氮物質(zhì)及其功能Table 2 Important nitrogenous products from amino acid metabolism and their functions in animals

續(xù)表2

2.4 功能性氨基酸對(duì)免疫功能的作用

蛋白質(zhì)的缺乏可損害動(dòng)物免疫功能,增加動(dòng)物對(duì)疾病的易感性,降低了許多血漿氨基酸的利用率,特別是谷氨酸、精氨酸、色氨酸和半胱氨酸[47]。谷氨酸、精氨酸和半胱氨酸增強(qiáng)免疫功能的作用現(xiàn)已被確定[48-49]。谷氨酸是淋巴細(xì)胞的主要能量物質(zhì)[50],為淋巴細(xì)胞的增殖和免疫功能所必需[49]。谷氨酸還能提高噬菌細(xì)胞的噬菌活性,刺激T-淋巴細(xì)胞產(chǎn)生細(xì)胞因子和B-淋巴細(xì)胞產(chǎn)生抗體[49,51]。半胱氨酸利用率的降低是限制谷胱甘肽、低分子量硫醇及一些關(guān)鍵抗氧化劑合成的主要因素[48]。因此,飼糧中添加N-乙酰半胱氨酸(一種穩(wěn)定的半胱氨酸前體)能大大提高處于各種疾病狀態(tài)下的動(dòng)物免疫功能[52]。精氨酸可誘導(dǎo)環(huán)烷油合成酶的合成,而環(huán)烷油是病原菌和病毒細(xì)胞的毒素[53]。前人試驗(yàn)結(jié)果已經(jīng)表明,飼糧中添加精氨酸能提高哺乳仔豬[54]和妊娠母豬免疫功能[55]。

近年來(lái),人們對(duì)色氨酸和脯氨酸的免疫功能產(chǎn)生了更濃厚的興趣?；加新苑窝椎呢i血漿色氨酸水平持續(xù)下降[5]。色氨酸分解代謝對(duì)巨噬細(xì)胞和淋巴細(xì)胞功能至關(guān)重要。據(jù)報(bào)道,口服色氨酸能增強(qiáng)先天免疫應(yīng)答[56]。鄰氨基苯甲酸(一種色氨酸代謝物,由吲哚胺2,3-加雙氧酶代謝途徑而來(lái))能抑制促炎癥反應(yīng)的輔助性T細(xì)胞-1因子和阻止自體免疫神經(jīng)性炎癥[57]。Ha等[58]發(fā)現(xiàn)由于小腸脯氨酸氧化酶缺乏而引起的脯氨酸代謝受阻損害腸道免疫系統(tǒng)。由脯氨酸氧化而來(lái)的主要介導(dǎo)物是過(guò)氧化氫,它是病原菌的細(xì)胞毒素,也是一種信號(hào)分子。據(jù)推測(cè),在胚胎和新生仔豬發(fā)育期間,豬胎盤和仔豬小腸高活性的脯氨酸氧化酶對(duì)保護(hù)胎兒和新生仔豬組織免受感染起到關(guān)鍵作用[31,59]。

3 小 結(jié)

功能性氨基酸是合成許多生物活性化合物的必需前體物質(zhì),對(duì)妊娠、哺乳期母豬和新生仔豬的健康、生長(zhǎng)、發(fā)育、繁殖及代謝等多方面起到重要的作用。因此,制定功能性氨基酸的母豬飼養(yǎng)計(jì)劃將更有利于其生產(chǎn)性能的發(fā)揮。但母豬飼糧的最佳功能性氨基酸需要量仍需作進(jìn)一步研究。

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