維生素A的介紹

1、第五章維 生 素 A1Vitamin A History Ancient Egypt - cure night blindness by topical application of liver to eye Ancient Greeks - cure by eating liver 孫思邈(581-682年) 首先用豬肝治療“雀目”(夜盲癥) 1913 - 2 groups purified fat soluble factor needed for growth of rats - McCollum and Davis found it was in butter or egg yolk,

2、 not lard - Osborn and Mendel, found in cod liver oil and butter 1930 - structure identified; conversion of -carotene to Vit. A2一、維生素A的性質(zhì)、吸收與代謝 維生素A亦名視黃醇(Retinol,VA),在自然界中的多是全反式棕櫚酸酯。它的衍生物具有特殊的生理功能，如視黃醛(Retinyl Aldehyde VA醛)對(duì)暗適應(yīng)有效；甘露糖視黃醇磷酸(Mannosyl Retiny Phosphate MRP)也具有某些生理功能。3維生素A衍生物的分子式4567 維生素A

3、及其衍生物易氧化。氧化劑MnO2可使之成為醛,還原劑可將維生素A酸還原為醛或醇。 對(duì)堿較穩(wěn)定,但對(duì)酸不穩(wěn)定,使其脫氫或?qū)㈦p鍵重新排列。 在光或碘的作用下,全反式可變?yōu)檩^穩(wěn)定的11順式異構(gòu)體，在強(qiáng)光下形成二聚體或多聚體。8-胡蘿卜素結(jié)構(gòu)式910-胡蘿卜素水解為維生素A11Structure of Vitamin A and -Carotene 1213類胡蘿卜素化合物的生物活性（以-胡蘿卜生物活性為100%）類胡蘿卜素 活性 類胡蘿卜素活性-胡蘿卜素 100 -半胡蘿卜素 有-胡蘿卜素 5054 -apo-8-胡蘿卜醛 72-胡蘿卜素 4250 -apo-8-胡蘿卜酸 有-新胡蘿卜素 2040

4、脫水葉黃素 213，4去氫-胡蘿卜素 75 玉米黃素（隱黃質(zhì)） 57-胡蘿卜素 21反-順異構(gòu)體比全反式的活性要小-胡蘿卜素 5014二、維生素A及胡蘿卜素的代謝 1.維生素A的吸收 維生素A的吸收為主動(dòng)吸收,需要能量,速率比胡蘿卜素要快730倍. 食物中的維生素A為酯式在胰液或絨毛刷狀緣中的視黃酯酶分解為游離式進(jìn)入到小腸壁在腸內(nèi)細(xì)胞微粒體中被酯酶所酯化,合成為維生素A棕櫚酯. 攝取維生素A35小時(shí)后,吸收達(dá)到高峰. 維生素A的吸收也需要膽鹽.1516171819 Intestinal Absorption - Dietary retinyl esters must be hydrolyzed

5、 pancreatic carboxyl(Cholesterol ester) hydrolase retinyl ester hydrolase - beta carotene carotene 15,15 dioxygenase Passive diffusion of retinol into enterocyte Re-esterification in enterocyte(palmitate and stearate) - LRAT(lecithin retinol acyl transterase) - ARAT(acyl-coA:retinol acyltransferase

6、Packaging into chylomicra with triglycerides, cholesterol esters20 2. 維生素A的儲(chǔ)存 維生素A與乳糜微粒相結(jié)合由淋巴系統(tǒng)輸送到肝。 酯式水解進(jìn)入肝,然后又再酯化為棕櫚酸酯。 肝實(shí)質(zhì)細(xì)胞負(fù)責(zé)攝取及新進(jìn)入的維生素A代謝,一部分維生素A由實(shí)質(zhì)細(xì)胞轉(zhuǎn)入類脂儲(chǔ)存細(xì)胞,這類細(xì)胞中有許多類脂滴,85%的維生素A在類脂滴中。213. 維生素A的運(yùn)輸 肝內(nèi)儲(chǔ)存維生素A酯經(jīng)酯酶水解為醇式，與視黃醇結(jié)合蛋白（Retionl Binding Proetin,RBP）結(jié)合，再與前白蛋白（Prealbumin,PA）結(jié)合，形成維生素A-RBP-PA復(fù)合

7、體后，才離開肝臟。經(jīng)血流入靶組織。 維生素A在一般情況下必須與蛋白質(zhì)結(jié)合，使之具有水溶性，并比較穩(wěn)定。 細(xì)胞膜對(duì)復(fù)合體有識(shí)別能力，但對(duì)未結(jié)合的維生素A無(wú)識(shí)別力，以致對(duì)維生素A的攝取失去控制，過多維生素A進(jìn)入細(xì)胞而產(chǎn)生毒性。 維生素A-RBP-PA復(fù)合體隨血流到腸粘膜、膀胱、角膜及上皮組織等靶細(xì)胞后，細(xì)胞膜上有RBP的特殊受體，可與RBP結(jié)合，并將維生素A釋放出來(lái)，進(jìn)入細(xì)胞內(nèi)。 維生素A進(jìn)入到靶細(xì)胞后，立即與細(xì)胞視黃醇結(jié)合蛋白（Cellular retinol Binding Protein,CRBP）相結(jié)合。 22Vitamin A, which circulates in the plasm

8、a as a complex with retinol-binding protein (RBP) leaves the binding protein, when the complex binds the cell surface receptor. The liberated retinol crosses the cell membrane via the receptor and is transferred to an intracellular binding protein, known as cellular retinol binding protein (CRBP). C

9、RBP then seems to deliver retinol to the target proteins that bring about the ultimate function. 23244. 維生素A的分解代謝及排出 視黃醇通過氧化轉(zhuǎn)變?yōu)榫S生素A酸，其中一部分異構(gòu)為順式。 大便中排出以葡糖視苷酸為主，為主要排出途徑。 尿中代謝產(chǎn)物一半為水溶性者，一半為脂溶性者。25維生素A的氧化代謝的可能途徑26維生素A的氧化代謝的可能途徑27285、胡蘿卜素的吸收 胡蘿卜素的微膠粒溶液在小腸內(nèi)吸收。 油溶液中者吸收最好，磷脂有助于形成微膠粒溶液而利于吸收。 膽鹽不但促進(jìn)胡蘿卜素運(yùn)輸至腸細(xì)胞，

10、助其與細(xì)胞表面相結(jié)合，并促進(jìn)胡蘿卜素的分解。 維生素E及其他抗氧化劑可保護(hù)側(cè)鏈的共軛雙鍵系統(tǒng)免于氧化。 胡蘿卜素吸收是擴(kuò)散性的，其吸收量與劑量大小有相反關(guān)系。 血漿中的類胡蘿卜素可分為-胡蘿卜素、葉黃素，番茄紅素及其他類胡蘿卜素，視攝入情況而定?？纱嬖谟诟?、脂肪、腎、皮膚及血管粥樣硬化的斑塊中。 29三、維生素A的生理功能 維生素A具有維持正常生長(zhǎng)、生殖、視覺及抗感染的功能，但其作用機(jī)理迄今尚未完全清楚。30311、維生素A與視覺的關(guān)系 視網(wǎng)膜上有兩種視細(xì)胞，即視桿細(xì)胞與視錐細(xì)胞，人類前者數(shù)量多，與暗視覺有關(guān)；后者數(shù)量少，與明視覺及色覺有關(guān)，他們都有視色素，由視蛋白與生色團(tuán)組成。 視桿細(xì)胞外段

11、含有視色素是感光部分。 323334視紫紅質(zhì)(rhodopsin)，由維生素A醛與視蛋白（opsin）結(jié)合而成。維生素A醛由維生素A氧化而來(lái)，經(jīng)異構(gòu)酶作用使其變?yōu)?1-順式維生素A醛。 維生素A醛由視蛋白之間的一級(jí)結(jié)構(gòu)是11-順維生素A醛的醛基與視蛋白中賴氨酸氨基形成希夫堿（Schiff base）鍵，隨之引起視蛋白高級(jí)結(jié)構(gòu)改變，產(chǎn)生相互保護(hù)的二級(jí)結(jié)構(gòu)，在黑暗中非常穩(wěn)定。 3536Vitamin A is almost exactly the same as one half of the yellow pigment in carrots, beta-carotene. Light caus

12、es vitamin A to change shape from the bend cis form to the straight trans form. Our eyes sense light by seeing this change in shape.37 當(dāng)光照時(shí)，一個(gè)視紫紅質(zhì)接受一個(gè)光子后，維生素A醛在11-C上轉(zhuǎn)成全反維生素A醛，視蛋白的立體構(gòu)形也發(fā)生變化. 維生素A醛又經(jīng)視細(xì)胞外端的維生素A還原酶使成其變?yōu)榫S生素A，然后由色素上皮細(xì)胞微粒體中酯酶將其酯化而儲(chǔ)存于色素上細(xì)胞內(nèi)，需要時(shí)再異構(gòu)為11-順維生素A。 暗適應(yīng)按上述相反方式進(jìn)行，又形成視紫紅質(zhì)。 383940 暗時(shí)Na

13、+從視桿細(xì)胞內(nèi)段移到外段，形成暗電流（Dark current flow）。當(dāng)視紫紅質(zhì)經(jīng)光異構(gòu)后變?yōu)榍肮庖曌霞t質(zhì)（Prelumirhodopsin）, 所結(jié)合的Ca2+在視桿細(xì)胞外段釋放出來(lái)，中止了Na+流動(dòng)及暗電流，其結(jié)果產(chǎn)生電壓的波動(dòng)，這種電位差使神經(jīng)刺激加強(qiáng)傳入腦中發(fā)生光感，也可用視網(wǎng)膜電圖測(cè)定。41(1)11-cis retinal and opsin in a rod cell combine to form Rhodopsin.(2/3) Chemical changes occur following the absorption of a photon of light.(4)

14、 After transduction occurs metarhodopsin II dissociates into all-trans retinal which isomerises as the cycle begins again.(5) The key step in the mechanism is step 3 the transduction of photon reception to a neural action potential. 4243 維生素A進(jìn)入到色素上皮細(xì)胞內(nèi)以酯式儲(chǔ)存于胞漿的油滴內(nèi)。 暗適應(yīng)的眼中，有一半的維生素A為11-順式，在視桿細(xì)胞的外段有少量的

15、游離維生素A，其中60%為11-順式，生理上很重要。 維生素A缺乏時(shí)，首先肝內(nèi)儲(chǔ)存的維生素A釋放供給其他組織，肝的儲(chǔ)存量下降，血漿維生素A正常。 當(dāng)肝儲(chǔ)存量將近空竭時(shí)，血漿維生素A水平才下降，但由于視網(wǎng)膜的色素上皮組織有維生素A積累，視紫紅質(zhì)的維生素A醛下降較慢。 色素上皮細(xì)胞內(nèi)維生素A缺乏時(shí)，才有夜盲癥出現(xiàn)。 44Retinol is transported to the retina via the circulation, where it moves into retinal pigment epithelial cells. There, retinol is esterified

16、to form a retinyl ester that can be stored. When needed, retinyl esters are broken apart (hydrolyzed) and isomerized to form 11-cis retinol, which can be oxidized to form 11-cis retinal. 11-cis Retinal can be shuttled to the rod cell, where it binds to a protein called opsin to form the visual pigme

17、nt, rhodopsin (visual purple). Absorption of a photon of light4546Night blindness is also an early symptom 47Xerophtalmia This is a range of disorders that affect the eye and that can lead to blindness. The symptoms of xerophthalmia occur in approximately the following order: Nightblindness: The chi

18、ld can not see in the dim light, making child to fall over things and can not see to eat. Bitots spots: These are foamy, soapy and whitish patches on the white part (the conjunctiva) of the eye. They don抰 affect the sight in day light. Conjunctiva xerosis: This means dryness, slightl roughness or wr

19、inkles in the white part of the eye, which are usually wet, smooth and shiny. Changes of the tear ducts also lead to reduced wettability of the eye. Corneal lesions: If the clear part of the eye is damaged the person can抰 see properly and may go blind. Blindness is a seriously irreversible change. I

20、t is important to recognise and treat early symptoms. Bitots spot 482、維生素A對(duì)糖蛋白合成的影響 缺乏維生素A的動(dòng)物的某些組織，如小腸、角膜、氣管上皮組織及血清等的特殊糖蛋白減少，給以維生素A或維生素A酸可以促進(jìn)其合成。 細(xì)胞膜表面的蛋白主要為糖蛋白，細(xì)胞膜的功能如接觸抑制、分化及識(shí)別環(huán)境的能力，可能與糖蛋白有關(guān)。 免疫球蛋白也是糖蛋白，維生素A營(yíng)養(yǎng)狀況影響免疫功能，可能與此有關(guān)。 49 維生素A在糖蛋白合成中變化分為三個(gè)步驟 (以甘露糖為例)形成維生素A磷酸酯（Retinylphosphate,RP）；由RP合成MRP(M

21、annosylretinyl phosphate,MRP) ，這一步驟在微粒體內(nèi)合成；將單糖轉(zhuǎn)移至糖蛋白上 50VA在糖蛋白合成中的作用 51 細(xì)胞膜表面蛋白主要是糖蛋白，糖蛋白的合成需要視黃醇，當(dāng)視黃醇缺乏時(shí)，糖蛋白合成受阻，黏膜上皮的正常結(jié)構(gòu)和功能改變，上皮組織發(fā)生鱗狀角化。523、清除自由基 -胡蘿卜素有很好的抗氧化作用，能通過提供電子抑制活性氧的生成達(dá)到清除自由基的目的。 -胡蘿卜素與維生素E兩者在抑制脂質(zhì)過氧化反應(yīng)過程中有協(xié)同增效作用。5354四、維生素A的需要量中國(guó)RDA成人每日800g.其中1/3最好來(lái)自視黃醇,即266 g; 2/3可為-胡蘿卜素,應(yīng)為5346=3204 g.5

22、5中國(guó)居民膳食維生素A推薦攝入量(RNI)年齡（歲）RNI*(gRE)年齡（歲）RNI*(gRE)040014男 800女 7000.5400188007001500孕婦： 初期8004600 中期9007700 晚期90011700乳母1200注：* 建議兒童及成人膳食維生素A約1/31/2以上來(lái)自動(dòng)物性食物；但孕婦膳食維生素A來(lái)源應(yīng)以植物性食物為主。 56Life Stage GroupRDA/AI* g/dayUL g/dayInfants 06 months712 months400*500*600600Children 13 years48 years300400600900Male

23、s 913 years1418 years19 - 70 years600900900170028003000Females 913 years1418 years19 - 70 years600700700170028003000Pregnancy 50 years75077028003000Lactation 50 years120013002800300057五、維生素缺乏癥 Vitamin A deficiency is a public health problem in 118 countries, especially in Africa and South-East Asia,

24、 once again hitting hardest young children and pregnant women in low-income countries. Crucial for maternal and child survival, supplying adequate vitamin A in high-risk areas can significantly reduce mortality. Conversely, its absence causes a needlessly high risk of disease and death. 5859Vitamin-

25、A DeficiencyEarly Stage Vitamin-A DeficiencyLate Stage 606162A few salient facts Between 100 and 140 million children are vitamin A deficient.An estimated 250 000 to 500 000 vitamin A-deficient children become blind every year, half of them dying within 12 months of losing their sight.Nearly 600 000

26、 women die from childbirth-related causes each year, the vast majority of them from complications which could be reduced through better nutrition, including provision of vitamin A.63Breastfeeding. Breast milk is a natural source of vitamin A. Promoting breastfeeding is the best way to protect babies

27、 from VAD.Vitamin A supplementation. For deficient children, the periodic supply of high-dose vitamin A in swift, simple, low-cost, high-benefit interventions has also produced remarkable results, reducing mortality by 23% overall and by up to 50% for acute measles sufferers.64Food fortification. Ta

28、king over where supplementation leaves off, food fortification (e.g. sugar in Guatemala) maintains vitamin A status, especially for high-risk groups and needy families.Home gardens. For vulnerable rural families (e.g. in Africa and South-East Asia), growing fruits and vegetables in home gardens complements dietary diversification and fortification and contributes to bette