叶酸

叶酸
	IUPAC名; (2S)-2-[[4-[(2-amino-4-oxo-1H-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid; (2S)-2-[[4-[(2-氨基-4-氧代-1H-6-蝶啶基)甲氨基]苯甲基]氨基]戊二酸
别名	pteroyl-L-glutamic acid; vitamin B9, vitamin M; folacin, folic acid
识别
CAS号	59-30-3
SMILES	O=C(N[C@H](C(O)=O)CCC(O)=O)C1=CC=C(NCC2=NC(C(NC(N)=N3)=O)=C3N=C2)C=C1;
RTECS	LP5425000
性质
化学式	C19H19N7O6
摩尔质量	441.403 g·mol⁻¹
外观	橙黄色结晶
熔点	250 ℃ (523 K) 分解
溶解性（水）	2.5mg/l（20 ℃）
pKa	pKa1 : 2.3, pKa2 : 8.3
	若非注明，所有数据均出自一般条件（25 ℃，100 kPa）下。

叶酸
系统（IUPAC）命名名称
	(2S)-2-[[4-[(2-Amino-4-oxo-1H-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid
临床数据
读音	foe' lik
Drugs.com	Monograph
MedlinePlus	a682591
妊娠分级	US: A (人类研究中表明无风险) ; ;
给药途径	By mouth, IM, IV, sub-Q
合法状态
合法状态	US: OTC ;
药代动力学数据
生物利用度	50–100%
代谢	肝脏
排泄	肾脏
识别信息
CAS注册号	59-30-3
ATC代码	B03BB01
PubChem	CID 6037
IUPHAR/BPS	4563
DrugBank	DB00158
ChemSpider	5815
UNII	935E97BOY8
KEGG	C00504
ChEBI	CHEBI:27470
ChEMBL	CHEMBL1622
其他名称	FA, N-(4-{[(2-amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamic acid, pteroyl-L-glutamic acid, vitamin B9,vitamin Bc,vitamin M,folacin, pteroyl-L-glutamate
化学信息
化学式	C19H19N7O6
摩尔质量	441.40 g·mol−1
	SMILES n1c2C(=O)NC(N)=Nc2ncc1CNc3ccc(cc3)C(=O)N[C@H](C(O)=O)CCC(O)=O; ;
	InChI InChI=1S/C19H19N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,8,12,21H,5-7H2,(H,24,29)(H,27,28)(H,31,32)(H3,20,22,25,26,30)/t12-/m0/s1; Key:OVBPIULPVIDEAO-LBPRGKRZSA-N;
物理性质
熔点	250 °C（482 °F）（分解）
水溶液	1.6 mg/L (25 °C) mg/mL (20 °C)

叶酸（Folate、folic acid）也称为维生素B₉、维生素M、维生素B_c、蝶酰谷氨酸，属于维生素B的一种^[2]。叶酸可用于治疗由叶酸缺乏症引起的贫血^[2]。叶酸也是孕妇的营养补充品^[2]^[7]。在新生儿的神经管缺损病例中，有超过一半被认为肇因怀孕初期叶酸摄取不足所致^[8]。有超过50个国家利用加入叶酸的营养强化食品来减少神经管缺损的比例^[9]^[10]。长期补充叶酸和中风及心血管疾病风险的小幅下降有关^[11]。叶酸可以口服，也可以用注射的方式补充^[2]。

正常剂量下的叶酸不会造成副作用^[2]，但还不确定长期的高剂量摄取是否有需要关注的问题^[2]。不过已知高剂量的叶酸摄取会让维生素B12缺乏症的问题较不易被检查到^[8]。人体在制造DNA、RNA，以及制造细胞分裂需要的氨基酸代谢时，都必须用到叶酸^[8]。因为人体无法自行制造叶酸，因此叶酸属于人体必需的维生素^[12]。

叶酸摄取不足会造成叶酸缺乏症^[8]，会导致巨母红血球性贫血^[8]，症状包括疲劳、心悸、呼吸困难、舌头上的疮，以及皮肤或发色的变化^[8]，儿童若膳食摄入不足，一个月后会出现叶酸缺乏症^[13]。成人体内正常的叶酸总量在10,000–30,000µg，而血液中的浓度则为7 nmol/L（3 ng/mL）^[8]。

叶酸是在1931年至1943年之间发现的^[14]，由米切尔（H．K．Mitchell，1941）及其同事^[15]首次从菠菜叶中提取纯化出来，命名为叶酸^[16]。叶酸列在世界卫生组织基本药物标准清单中，是基础公卫体系中所需，最有效及安全的药物^[17]。2014年在开发中国家，每一剂的叶酸膳食补充品价格在0.001至0.005美金之间^[18]。叶酸的英文folic源自拉丁文的folium，意思就是叶子^[19]。在许多的食物中都含有叶酸，特别是深绿色的叶菜类以及肝^[8]。

对孕妇的重要性

由于叶酸对于神经管的形成有重要作用，因此孕妇在怀孕前摄入足够的叶酸对于胎儿的正常发育很重要。怀孕期间缺乏叶酸能够影响胎儿神经系统的发育。研究表明在怀孕前期和怀孕中补充足够的叶酸能够降低神经管畸形和唇裂胎儿的出生率^[20]。美国全国环境卫生科学研究所的研究人员在新一期《新英格兰医学杂志》上报告说，孕妇补充叶酸可防婴儿唇裂，但对于预防颚裂作用似乎不太明显^[21]。

自1998年1月1日起，美国已强制规定在某些谷物食品中强化叶酸，FDA规定每1KG谷物食品（面包、面粉、早餐谷物、大米等）强化1.4mg叶酸（美国卫生及公共服务部，1996年）。^[22]
加拿大、澳大利亚、墨西哥以及智利等国随后也效仿美国推行“叶酸强化”叶酸另外可以帮助乳汁增加细胞。^{[来源请求]}
70%接受调查的西班牙孕妇，没有补充叶酸。 ^[23]

叶酸的食物来源

从叶酸最初的提取和名称就能知道，叶酸大量存在于带叶的蔬菜中。菠菜、芦笋、芜菁、小白菜、莴苣、抱子甘蓝、花椰菜、黄豆、玉米、扁豆、豌豆、葵花籽的粗粮及其他带叶的蔬菜。水果包括哈密瓜、蜜瓜、香蕉、木莓、葡萄柚、草莓、以及橙汁、罐装菠萝汁、番茄汁等。动物食品如动物的肝脏、肾脏、禽肉及蛋类，如猪肝、鸡肉、牛肉、羊肉等也含有丰富的叶酸。但是由于烹饪时的高温对于叶酸的破坏和人体吸收效率不高的原因，日常饮食还是较难满足孕妇的叶酸需要。所以孕妇在怀孕期间（甚至怀孕前）补充人工合成的叶酸药物是必要的。^{[来源请求]}有研究表明男性服用叶酸也能增加精子的质量-减少染色体缺陷从而降低新生儿唐氏综合征发生的几率^[24]。

每日摄入量

国家卫生部及美国疾病控制中心均给出指导建议：孕妇建议每日摄入量0.4毫克，绝对不能随便选用大剂量的叶酸增补剂。^{[来源请求]}

美国国家医学院(IOM)建议成年人每日叶酸摄取量安全上限为1毫克，即1000微克。^[25]

叶酸药物要保存在干燥避光阴凉的地方。因为叶酸见水、见光都会分解。 WHO推荐孕妇每日摄入量为：0.4mg/day^[11]

参考文献

引用

↑ Folic Acid. The PubChem Project. [2017-12-18].
↑ ^2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 ^2.6 ^2.7 ^2.8 Folic Acid. Drugs.com. American Society of Health-System Pharmacists. 2010-01-01 [2016-09-01].
↑ Fenech, Michael. Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2012-05, 733 (1–2): 21–33. PMID 22093367. doi:10.1016/j.mrfmmm.2011.11.003.
↑ Definition of vitamin Bc. Medical-dictionary.thefreedictionary.com. [2012-09-09].
↑ Darby, William J.; Jones, Edgar. Treatment of Sprue with Synthetic L. casei Factor (Folic Acid, Vitamin M).. Experimental Biology and Medicine. 1945-11-01, 60 (2): 259–262 [2014-12-13]. doi:10.3181/00379727-60-15154P.
↑ Folic Acid, The PubChem Project, [2014-08-19]
↑ Bibbins-Domingo, Kirsten; Grossman, David C.; Curry, Susan J.; Davidson, Karina W.; Epling, John W.; García, Francisco A.R.; Kemper, Alex R.; Krist, Alex H.; Kurth, Ann E.; Landefeld, C. Seth; Mangione, Carol M.; Phillips, William R.; Phipps, Maureen G.; Pignone, Michael P.; Silverstein, Michael; Tseng, Chien-Wen. Folic Acid Supplementation for the Prevention of Neural Tube Defects. JAMA. 2017-01-10, 317 (2): 183. doi:10.1001/jama.2016.19438.
↑ ^8.0 ^8.1 ^8.2 ^8.3 ^8.4 ^8.5 ^8.6 ^8.7 Dietary supplement fact sheet: Folate. Health Information. Office of Dietary Supplements, US National Institutes of Health. [2016-09-01].
↑ Bailey, Lynn B. Folate in Health and Disease, Second Edition. CRC Press. 2009: 198. ISBN 9781420071252 （英语）.
↑ Obeid, R; Herrmann, W. The emerging role of unmetabolized folic acid in human diseases: myth or reality?. Current drug metabolism. 2012-10, 13 (8): 1184–95. PMID 22746304.
↑ Li Y, Huang T, Zheng Y, Muka T, Troup J, Hu FB. Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2016, 5 (8): e003768. PMC 5015297 . PMID 27528407. doi:10.1161/JAHA.116.003768.
↑ Pommerville, Glendale Community College Jeffrey C. Alcamo's Fundamentals of Microbiology: Body Systems. Jones & Bartlett Publishers. 2009: 511. ISBN 9780763787127 （英语）.
↑ Marino, Bradley S.; Fine, Katie Snead. Blueprints Pediatrics. Lippincott Williams & Wilkins. 2009: 131. ISBN 9780781782517 （英语）.
↑ Pond, Wilson G.; Nichols, Buford L.; Brown, Dan L. Adequate Food for All: Culture, Science, and Technology of Food in the 21st Century. CRC Press. 2009: 148. ISBN 9781420077544 （英语）.
↑ Mitchell HK, Snell EE, Williams RJ (1941). "The concentration of "folic acid"". J Am Chem Soc. 63 (8): 2284.[doi:10.1021/ja01853a512]
↑ Hoffbrand AV & Weir DG (2001) The history of folic acid. Br J Haematol 113, 579-589.
↑ WHO Model List of Essential Medicines (19th List) (PDF). World Health Organization. 2015-04 [2016-12-08].
↑ Folic Acid. International Drug Price Indicator Guide. [2016-09-01]. ^{[永久失效链接]}
↑ Chambers Concise Dictionary. Allied Publishers. 2004: 451. ISBN 979-8186-06236-3 （英语）.
↑ Goh YI & Koren G (2008) Folic acid in pregnancy and fetal outcomes. J Obstet Gynaecol 28, 3-13
↑ 存档副本. [2008-08-27].
↑ 中国营养学会. 《中国居民膳食营养素参考摄入量》. 北京: 中国轻工业出版社. 2006年2月: 356. ISBN 9787501928958 （简体中文）.
↑ El 80% de las mujeres no acuden al médico para planificar el embarazo (新闻稿). EL Pais. 2013-09-10 [2013-10-10] （西班牙语）.
↑ Medical News: Extra Folate for Men May Reduce Birth Defects - in Care, Diet & Nutrition from MedPage Today
↑ Institute of Medicine (US) Food and Nutrition Board. Dietary Reference Intakes: A Risk Assessment Model for Establishing Upper Intake Levels for Nutrients, Institute of Medicine, 1998. Washington, DC: National Academies Press (US). 1998: 第57页. ISBN 9787501928958 （英语）.

来源

http://www.who.int/elena/titles/guidance_summaries/daily_iron_pregnancy/en/
This article contains information from the public domain resource at http://ods.od.nih.gov/factsheets/Folate-HealthProfessional/
Herbert V. Folic Acid. Shils ME, Olson J, Shike M, Ross AC (编). Modern nutrition in health and disease 9th. Baltimore: Williams and Wilkins. 1999. ISBN 0-683-30769-X.
Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B₆, folate, vitamin B₁₂, pantothenic acid, biotin, and choline / a report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients. Washington, D.C.: National Academy Press. 1998. ISBN 0-309-06554-2.
Dietary Guidelines Advisory Committee, Agricultural Research Service, United States Department of Agriculture (USDA). Report of the Dietary Guidelines Advisory Committee on the Dietary Guidelines for Americans, 2010. https://web.archive.org/web/20110317053443/http://www.cnpp.usda.gov/DGAs2010-DGACReport.htm

外部链接

生物化学链接

[1] Folic Acid. The PubChem Project. [2017-12-18].

[AHFS2016-2] 2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 ^2.6 ^2.7 ^2.8 Folic Acid. Drugs.com. American Society of Health-System Pharmacists. 2010-01-01 [2016-09-01].

[Folate_2011-3] Fenech, Michael. Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2012-05, 733 (1–2): 21–33. PMID 22093367. doi:10.1016/j.mrfmmm.2011.11.003.

[Definition_of_vitamin_Bc-4] Definition of vitamin Bc. Medical-dictionary.thefreedictionary.com. [2012-09-09].

[darby1945-5] Darby, William J.; Jones, Edgar. Treatment of Sprue with Synthetic L. casei Factor (Folic Acid, Vitamin M).. Experimental Biology and Medicine. 1945-11-01, 60 (2): 259–262 [2014-12-13]. doi:10.3181/00379727-60-15154P.

[6] Folic Acid, The PubChem Project, [2014-08-19]

[USPSTF2017-7] Bibbins-Domingo, Kirsten; Grossman, David C.; Curry, Susan J.; Davidson, Karina W.; Epling, John W.; García, Francisco A.R.; Kemper, Alex R.; Krist, Alex H.; Kurth, Ann E.; Landefeld, C. Seth; Mangione, Carol M.; Phillips, William R.; Phipps, Maureen G.; Pignone, Michael P.; Silverstein, Michael; Tseng, Chien-Wen. Folic Acid Supplementation for the Prevention of Neural Tube Defects. JAMA. 2017-01-10, 317 (2): 183. doi:10.1001/jama.2016.19438.

[NIH2016-8] 8.0 ^8.1 ^8.2 ^8.3 ^8.4 ^8.5 ^8.6 ^8.7 Dietary supplement fact sheet: Folate. Health Information. Office of Dietary Supplements, US National Institutes of Health. [2016-09-01].

[9] Bailey, Lynn B. Folate in Health and Disease, Second Edition. CRC Press. 2009: 198. ISBN 9781420071252 （英语）.

[10] Obeid, R; Herrmann, W. The emerging role of unmetabolized folic acid in human diseases: myth or reality?. Current drug metabolism. 2012-10, 13 (8): 1184–95. PMID 22746304.

[Li2016-11] Li Y, Huang T, Zheng Y, Muka T, Troup J, Hu FB. Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2016, 5 (8): e003768. PMC 5015297 . PMID 27528407. doi:10.1161/JAHA.116.003768.

[12] Pommerville, Glendale Community College Jeffrey C. Alcamo's Fundamentals of Microbiology: Body Systems. Jones & Bartlett Publishers. 2009: 511. ISBN 9780763787127 （英语）.

[13] Marino, Bradley S.; Fine, Katie Snead. Blueprints Pediatrics. Lippincott Williams & Wilkins. 2009: 131. ISBN 9780781782517 （英语）.

[14] Pond, Wilson G.; Nichols, Buford L.; Brown, Dan L. Adequate Food for All: Culture, Science, and Technology of Food in the 21st Century. CRC Press. 2009: 148. ISBN 9781420077544 （英语）.

[15] Mitchell HK, Snell EE, Williams RJ (1941). "The concentration of "folic acid"". J Am Chem Soc. 63 (8): 2284.[doi:10.1021/ja01853a512]

[16] Hoffbrand AV & Weir DG (2001) The history of folic acid. Br J Haematol 113, 579-589.

[WHO19th-17] WHO Model List of Essential Medicines (19th List) (PDF). World Health Organization. 2015-04 [2016-12-08].

[18] Folic Acid. International Drug Price Indicator Guide. [2016-09-01]. ^{[永久失效链接]}

[19] Chambers Concise Dictionary. Allied Publishers. 2004: 451. ISBN 979-8186-06236-3 （英语）.

[20] Goh YI & Koren G (2008) Folic acid in pregnancy and fetal outcomes. J Obstet Gynaecol 28, 3-13

[21] 存档副本. [2008-08-27].

[22] 中国营养学会. 《中国居民膳食营养素参考摄入量》. 北京: 中国轻工业出版社. 2006年2月: 356. ISBN 9787501928958 （简体中文）.

[23] El 80% de las mujeres no acuden al médico para planificar el embarazo (新闻稿). EL Pais. 2013-09-10 [2013-10-10] （西班牙语）.

[24] Medical News: Extra Folate for Men May Reduce Birth Defects - in Care, Diet & Nutrition from MedPage Today

[25] Institute of Medicine (US) Food and Nutrition Board. Dietary Reference Intakes: A Risk Assessment Model for Establishing Upper Intake Levels for Nutrients, Institute of Medicine, 1998. Washington, DC: National Academies Press (US). 1998: 第57页. ISBN 9787501928958 （英语）.

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叶酸


IUPAC名 (2S)-2-[[4-[(2-amino-4-oxo-1H-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid^[6] (2S)-2-[[4-[(2-氨基-4-氧代-1H-6-蝶啶基)甲氨基]苯甲基]氨基]戊二酸
别名	pteroyl-L-glutamic acid; vitamin B₉, vitamin M; folacin, folic acid
识别
CAS号	59-30-3
SMILES	O=C(N[C@H](C(O)=O)CCC(O)=O)C1=CC=C(NCC2=NC(C(NC(N)=N3)=O)=C3N=C2)C=C1
RTECS	LP5425000
性质
化学式	C₁₉H₁₉N₇O₆
摩尔质量	441.403 g·mol⁻¹
外观	橙黄色结晶
熔点	250 ℃ (523 K) 分解
溶解性（水）	2.5mg/l（20 ℃）
pK_a	pK_a₁ : 2.3, pK_a₂ : 8.3
若非注明，所有数据均出自一般条件（25 ℃，100 kPa）下。