维生素A的介绍

1、第五章维 生 素 A1Vitamin A History Ancient Egypt - cure night blindness by topical application of liver to eye Ancient Greeks - cure by eating liver 孙思邈(581-682年) 首先用猪肝治疗“雀目”(夜盲症) 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、维生素A的性质、吸收与代谢 维生素A亦名视黄醇(Retinol,VA),在自然界中的多是全反式棕榈酸酯。它的衍生物具有特殊的生理功能，如视黄醛(Retinyl Aldehyde VA醛)对暗适应有效；甘露糖视黄醇磷酸(Mannosyl Retiny Phosphate MRP)也具有某些生理功能。3维生素A衍生物的分子式4567 维生素A

3、及其衍生物易氧化。氧化剂MnO2可使之成为醛,还原剂可将维生素A酸还原为醛或醇。 对碱较稳定,但对酸不稳定,使其脱氢或将双键重新排列。 在光或碘的作用下,全反式可变为较稳定的11顺式异构体，在强光下形成二聚体或多聚体。8-胡萝卜素结构式910-胡萝卜素水解为维生素A11Structure of Vitamin A and -Carotene 1213类胡萝卜素化合物的生物活性（以-胡萝卜生物活性为100%）类胡萝卜素 活性 类胡萝卜素活性-胡萝卜素 100 -半胡萝卜素 有-胡萝卜素 5054 -apo-8-胡萝卜醛 72-胡萝卜素 4250 -apo-8-胡萝卜酸 有-新胡萝卜素 2040

4、脱水叶黄素 213，4去氢-胡萝卜素 75 玉米黄素（隐黄质） 57-胡萝卜素 21反-顺异构体比全反式的活性要小-胡萝卜素 5014二、维生素A及胡萝卜素的代谢 1.维生素A的吸收 维生素A的吸收为主动吸收,需要能量,速率比胡萝卜素要快730倍. 食物中的维生素A为酯式在胰液或绒毛刷状缘中的视黄酯酶分解为游离式进入到小肠壁在肠内细胞微粒体中被酯酶所酯化,合成为维生素A棕榈酯. 摄取维生素A35小时后,吸收达到高峰. 维生素A的吸收也需要胆盐.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. 维生素A的储存 维生素A与乳糜微粒相结合由淋巴系统输送到肝。 酯式水解进入肝,然后又再酯化为棕榈酸酯。 肝实质细胞负责摄取及新进入的维生素A代谢,一部分维生素A由实质细胞转入类脂储存细胞,这类细胞中有许多类脂滴,85%的维生素A在类脂滴中。213. 维生素A的运输 肝内储存维生素A酯经酯酶水解为醇式，与视黄醇结合蛋白（Retionl Binding Proetin,RBP）结合，再与前白蛋白（Prealbumin,PA）结合，形成维生素A-RBP-PA复合

7、体后，才离开肝脏。经血流入靶组织。 维生素A在一般情况下必须与蛋白质结合，使之具有水溶性，并比较稳定。 细胞膜对复合体有识别能力，但对未结合的维生素A无识别力，以致对维生素A的摄取失去控制，过多维生素A进入细胞而产生毒性。 维生素A-RBP-PA复合体随血流到肠粘膜、膀胱、角膜及上皮组织等靶细胞后，细胞膜上有RBP的特殊受体，可与RBP结合，并将维生素A释放出来，进入细胞内。 维生素A进入到靶细胞后，立即与细胞视黄醇结合蛋白（Cellular retinol Binding Protein,CRBP）相结合。 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. 维生素A的分解代谢及排出 视黄醇通过氧化转变为维生素A酸，其中一部分异构为顺式。 大便中排出以葡糖视苷酸为主，为主要排出途径。 尿中代谢产物一半为水溶性者，一半为脂溶性者。25维生素A的氧化代谢的可能途径26维生素A的氧化代谢的可能途径27285、胡萝卜素的吸收 胡萝卜素的微胶粒溶液在小肠内吸收。 油溶液中者吸收最好，磷脂有助于形成微胶粒溶液而利于吸收。 胆盐不但促进胡萝卜素运输至肠细胞，

10、助其与细胞表面相结合，并促进胡萝卜素的分解。 维生素E及其他抗氧化剂可保护侧链的共轭双键系统免于氧化。 胡萝卜素吸收是扩散性的，其吸收量与剂量大小有相反关系。 血浆中的类胡萝卜素可分为-胡萝卜素、叶黄素，番茄红素及其他类胡萝卜素，视摄入情况而定。可存在于肝、脂肪、肾、皮肤及血管粥样硬化的斑块中。 29三、维生素A的生理功能 维生素A具有维持正常生长、生殖、视觉及抗感染的功能，但其作用机理迄今尚未完全清楚。30311、维生素A与视觉的关系 视网膜上有两种视细胞，即视杆细胞与视锥细胞，人类前者数量多，与暗视觉有关；后者数量少，与明视觉及色觉有关，他们都有视色素，由视蛋白与生色团组成。 视杆细胞外段

11、含有视色素是感光部分。 323334视紫红质(rhodopsin)，由维生素A醛与视蛋白（opsin）结合而成。维生素A醛由维生素A氧化而来，经异构酶作用使其变为11-顺式维生素A醛。 维生素A醛由视蛋白之间的一级结构是11-顺维生素A醛的醛基与视蛋白中赖氨酸氨基形成希夫碱（Schiff base）键，随之引起视蛋白高级结构改变，产生相互保护的二级结构，在黑暗中非常稳定。 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 当光照时，一个视紫红质接受一个光子后，维生素A醛在11-C上转成全反维生素A醛，视蛋白的立体构形也发生变化. 维生素A醛又经视细胞外端的维生素A还原酶使成其变为维生素A，然后由色素上皮细胞微粒体中酯酶将其酯化而储存于色素上细胞内，需要时再异构为11-顺维生素A。 暗适应按上述相反方式进行，又形成视紫红质。 383940 暗时Na

13、+从视杆细胞内段移到外段，形成暗电流（Dark current flow）。当视紫红质经光异构后变为前光视紫红质（Prelumirhodopsin）, 所结合的Ca2+在视杆细胞外段释放出来，中止了Na+流动及暗电流，其结果产生电压的波动，这种电位差使神经刺激加强传入脑中发生光感，也可用视网膜电图测定。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 维生素A进入到色素上皮细胞内以酯式储存于胞浆的油滴内。 暗适应的眼中，有一半的维生素A为11-顺式，在视杆细胞的外段有少量的

15、游离维生素A，其中60%为11-顺式，生理上很重要。 维生素A缺乏时，首先肝内储存的维生素A释放供给其他组织，肝的储存量下降，血浆维生素A正常。 当肝储存量将近空竭时，血浆维生素A水平才下降，但由于视网膜的色素上皮组织有维生素A积累，视紫红质的维生素A醛下降较慢。 色素上皮细胞内维生素A缺乏时，才有夜盲症出现。 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、维生素A对糖蛋白合成的影响 缺乏维生素A的动物的某些组织，如小肠、角膜、气管上皮组织及血清等的特殊糖蛋白减少，给以维生素A或维生素A酸可以促进其合成。 细胞膜表面的蛋白主要为糖蛋白，细胞膜的功能如接触抑制、分化及识别环境的能力，可能与糖蛋白有关。 免疫球蛋白也是糖蛋白，维生素A营养状况影响免疫功能，可能与此有关。 49 维生素A在糖蛋白合成中变化分为三个步骤 (以甘露糖为例)形成维生素A磷酸酯（Retinylphosphate,RP）；由RP合成MRP(M

21、annosylretinyl phosphate,MRP) ，这一步骤在微粒体内合成；将单糖转移至糖蛋白上 50VA在糖蛋白合成中的作用 51 细胞膜表面蛋白主要是糖蛋白，糖蛋白的合成需要视黄醇，当视黄醇缺乏时，糖蛋白合成受阻，黏膜上皮的正常结构和功能改变，上皮组织发生鳞状角化。523、清除自由基 -胡萝卜素有很好的抗氧化作用，能通过提供电子抑制活性氧的生成达到清除自由基的目的。 -胡萝卜素与维生素E两者在抑制脂质过氧化反应过程中有协同增效作用。5354四、维生素A的需要量中国RDA成人每日800g.其中1/3最好来自视黄醇,即266 g; 2/3可为-胡萝卜素,应为5346=3204 g.5

22、5中国居民膳食维生素A推荐摄入量(RNI)年龄（岁）RNI*(gRE)年龄（岁）RNI*(gRE)040014男 800女 7000.5400188007001500孕妇： 初期8004600 中期9007700 晚期90011700乳母1200注：* 建议儿童及成人膳食维生素A约1/31/2以上来自动物性食物；但孕妇膳食维生素A来源应以植物性食物为主。 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、维生素缺乏症 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