非对称性二甲基精氨酸

非对称性二甲基精氨酸
	若非注明，所有数据均出自标准状态（25 ℃，100 kPa）下。

非对称性二甲基精氨酸（英文：Asymmetric dimethylarginine，简称ADMA）是一种自然存在于血浆内的化合物。它是在人体细胞内细胞质中发生的蛋白质修饰过程产生的代谢副产物，与精氨酸有着密切关系。ADMA会影响精氨酸产生一氧化氮的过程，一氧化氮是对内皮细胞及心血管健康的物质。

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发现

非对称性二甲基精氨酸的介入角色首次在伦敦被发现^[1]，今天生物化学及临床研究继而发现ADMA与心血管疾病、糖尿病、阳痿及其他肾脏疾病的关系。ADMA亦在非常重要的—氧化氮路径有着重大的影响。

人体内的合成及调节

非对称性二甲基精氨酸是在蛋白质的后翻译修饰中，经由甲基化所生成。这个反应是由一群称为S-腺苷基蛋氨酸蛋白质N-甲基转移酶（蛋白质甲基酶I及II）所催化。^[2]组成ADMA的甲基，是由代谢高半胱氨酸的中间物：S-腺苷基蛋氨酸所释出（高半胱氨酸是一种重要的血液化合物，心血管疾病的基因标志）。在合成后，ADMA会移向细胞外的空间，并进入血浆内。ADMA可以利用高效液相层析仪来量度。

ADMA的浓度会受普通或氧化后的低密度脂蛋白胆固醇大量的提升。^[3]因此，高内皮低密度脂蛋白会提升ADMA值，出现了一个循环效应，并且阻碍了能令血管舒张的一氧化氮。要减少ADMA，需要透过排泄尿素及以二甲基精氨酸二甲胺水解酶（DDAH）代谢。在体内生成二甲基精氨酸二甲胺水解酶或多酚抗氧化剂亦可减少高半胱氨酸的水平，减低患有心血管疾病的风险。

与治疗学的关系

由于非对称性二甲基精氨酸的高水平会对身体有害，导致如心血管疾病、代谢疾病及其他老年的疾病等，所以降低ADMA水平有着重要的治疗成效。但是，现时仍未能有效地控制ADMA水平及临床的经验。

由于脂质调节的异常情况与ADMA有所关联，有建议摄取游离脂肪酸可以控制ADMA水平。但是，研究却未能证实此种说法。^[4]^[5]

ADMA亦与高半胱氨酸的上升有所关联。^[6]^[7]^[8]有猜测认为可以透过摄取叶酸来调节高半胱氨酸的水平，但研究却认为这未能提供任何临床的好处及维生素B会相反增加心血管的压力。^[9]^[10]^[11]

有建议指摄取精氨酸可以直接控制ADMA水平。^[12]^[13]这不单能促进内皮的功能，且能减少心血管疾病的临床病征。^[14]^[15]但是，有些研究在临床的结果上有着差异^[16]及在控制高半胱氨酸时须加倍留意病人的状况。

他汀除了能影响血液内的胆固醇水平外，亦能增加一氧化氮及对心脏供血的直接影响。ADMA的上升会影响他汀的效用及病人对他汀的反应。^[17]

内部链接

参考

[1]
Vallance P., Leone A., Calver A., Collier J., Moncada S. Endogenous dimethyl-arginine as an inhibitor of nitric oxide synthesis. J. Cardiovasc. Pharmacol. 1992, 20 (Suppli. 12): S60–S62.
[2]
Rawal N, Rajpurohit R, Lischwe MA, Williams KR, Paik WK, Kim S. Structural specificity of substrate for S-adenosylmethionine:protein arginine N-methyltransferases. Biochim Biophys Acta. 1995, 1248 (1): 11–8. PMID 7536038.
[3]
Boger RH, Sydow K, Borlak J, Thum T, Lenzen H, Schubert B, Tsikas D, Bode-Boger SM. LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases. Circ Res. 2000, 87 (2): 99–105 [2006-09-25]. PMID 10903992. （原始内容存档于2009-08-05）.
[4]
Eid HM, Arnesen H, Hjerkinn EM, Lyberg T, Ellingsen I, Seljeflot I. Effect of diet and omega-3 fatty acid intervention on asymmetric dimethylarginine. Nutr Metab (Lond). 2006, 3: 4 [2006-09-25]. PMID 16396682. （原始内容存档于2012-05-24）.
[5]
Namiranian K, Mittermayer F, Artwohl M, Pleiner J, Schaller G, Mayer BX, Bayerle-Eder M, Roden M, Baumgartner-Parzer S, Wolzt M. Free fatty acids do not acutely increase asymmetrical dimethylarginine concentrations. Horm Metab Res. 2005, 37 (12): 768–72. PMID 16372232.
[6]
Krzyzanowska K, Mittermayer F, Krugluger W, Schnack C, Hofer M, Wolzt M, Schernthaner G. Asymmetric dimethylarginine is associated with macrovascular disease and total homocysteine in patients with type 2 diabetes. Atherosclerosis. 2006. PMID 16414052.
[7]
Dayal S, Lentz SR. ADMA and hyperhomocysteinemia. Vasc Med. 2005,. 10 Suppl 1: S27–33. PMID 16444866.
[8]
Stuhlinger MC, Stanger O. Asymmetric dimethyl-L-arginine (ADMA): a possible link between homocyst(e)ine and endothelial dysfunction. Curr Drug Metab. 2005, 6 (1): 3–14. PMID 15720202.
[9]
Zoungas S, McGrath BP, Branley P, Kerr PG, Muske C, Wolfe R, Atkins RC, Nicholls K, Fraenkel M, Hutchison BG, Walker R, McNeil JJ. Cardiovascular morbidity and mortality in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) in chronic renal failure: a multicenter, randomized, controlled trial. J Am Coll Cardiol. 2006, 47 (6): 1108–16. PMID 16545638.
[10]
Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease (PDF). N Engl J Med. 2006 [2006-09-25]. PMID 16531613. （原始内容 (PDF)存档于2009-07-08）.
[11]
Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K. Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction (PDF). N Engl J Med. 2006 [2006-09-25]. PMID 16531614. （原始内容 (PDF)存档于2009-07-08）.
[12]
Bode-Boger SM, Muke J, Surdacki A, Brabant G, Boger RH, Frolich JC. Oral L-arginine improves endothelial function in healthy individuals older than 70 years. Vasc Med. 2003, 8 (2): 77–81. PMID 14518608.
[13]
John P. Cooke. The Cardiovascular Cure. Random House. 2002. ISBN 978-0-7679-0881-8.
[14]
Rector TS, Bank AJ, Mullen KA, Tschumperlin LK, Sih R, Pillai K, Kubo SH. Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure. Circulation. 1996, 93 (12): 2135–41 [2006-09-25]. PMID 8925582. （原始内容存档于2011-06-08）.
[15]
Ceremuzynski L, Chamiec T, Herbaczynska-Cedro K. Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris. Am J Cardiol. 1997, 80 (3): 331–3. PMID 9264427.
[16]
Loscalzo J. L-arginine and atherothrombosis. J Nutr. 2004, 134 (10 Suppl): 2798S–2800S; discussion 2818S–2819S. PMID 15465788. （原始内容存档于2004-12-10）.
[17]
Janatuinen T, Laakso J, Laaksonen R, Vesalainen R, Nuutila P, Lehtimaki T, Raitakari OT, Knuuti J. Plasma asymmetric dimethylarginine modifies the effect of pravastatin on myocardial blood flow in young adults. Vasc Med. 2003, 8 (3): 185–9. PMID 14989559.

外部链接

[1] [1]
Vallance P., Leone A., Calver A., Collier J., Moncada S. Endogenous dimethyl-arginine as an inhibitor of nitric oxide synthesis. J. Cardiovasc. Pharmacol. 1992, 20 (Suppli. 12): S60–S62.

[2] [2]
Rawal N, Rajpurohit R, Lischwe MA, Williams KR, Paik WK, Kim S. Structural specificity of substrate for S-adenosylmethionine:protein arginine N-methyltransferases. Biochim Biophys Acta. 1995, 1248 (1): 11–8. PMID 7536038.

[3] [3]
Boger RH, Sydow K, Borlak J, Thum T, Lenzen H, Schubert B, Tsikas D, Bode-Boger SM. LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases. Circ Res. 2000, 87 (2): 99–105 [2006-09-25]. PMID 10903992. （原始内容存档于2009-08-05）.

[NutrMetab2006-Eid-4] [4]
Eid HM, Arnesen H, Hjerkinn EM, Lyberg T, Ellingsen I, Seljeflot I. Effect of diet and omega-3 fatty acid intervention on asymmetric dimethylarginine. Nutr Metab (Lond). 2006, 3: 4 [2006-09-25]. PMID 16396682. （原始内容存档于2012-05-24）.

[HormMetabRes2005-Namiranian-5] [5]
Namiranian K, Mittermayer F, Artwohl M, Pleiner J, Schaller G, Mayer BX, Bayerle-Eder M, Roden M, Baumgartner-Parzer S, Wolzt M. Free fatty acids do not acutely increase asymmetrical dimethylarginine concentrations. Horm Metab Res. 2005, 37 (12): 768–72. PMID 16372232.

[Atherosclerosis2006-Krzyzanowska-6] [6]
Krzyzanowska K, Mittermayer F, Krugluger W, Schnack C, Hofer M, Wolzt M, Schernthaner G. Asymmetric dimethylarginine is associated with macrovascular disease and total homocysteine in patients with type 2 diabetes. Atherosclerosis. 2006. PMID 16414052.

[VascMed2006-Dayal-7] [7]
Dayal S, Lentz SR. ADMA and hyperhomocysteinemia. Vasc Med. 2005,. 10 Suppl 1: S27–33. PMID 16444866.

[CurrDrugMetab2005-Stuhlinger-8] [8]
Stuhlinger MC, Stanger O. Asymmetric dimethyl-L-arginine (ADMA): a possible link between homocyst(e)ine and endothelial dysfunction. Curr Drug Metab. 2005, 6 (1): 3–14. PMID 15720202.

[JAmCollCardiol2006-Zoungas-9] [9]
Zoungas S, McGrath BP, Branley P, Kerr PG, Muske C, Wolfe R, Atkins RC, Nicholls K, Fraenkel M, Hutchison BG, Walker R, McNeil JJ. Cardiovascular morbidity and mortality in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) in chronic renal failure: a multicenter, randomized, controlled trial. J Am Coll Cardiol. 2006, 47 (6): 1108–16. PMID 16545638.

[NEJM2006a-10] [10]
Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease (PDF). N Engl J Med. 2006 [2006-09-25]. PMID 16531613. （原始内容 (PDF)存档于2009-07-08）.

[NEJM2006-Bonna-11] [11]
Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K. Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction (PDF). N Engl J Med. 2006 [2006-09-25]. PMID 16531614. （原始内容 (PDF)存档于2009-07-08）.

[VascMed2003-Bode-Boger-12] [12]
Bode-Boger SM, Muke J, Surdacki A, Brabant G, Boger RH, Frolich JC. Oral L-arginine improves endothelial function in healthy individuals older than 70 years. Vasc Med. 2003, 8 (2): 77–81. PMID 14518608.

[13] [13]
John P. Cooke. The Cardiovascular Cure. Random House. 2002. ISBN 978-0-7679-0881-8.

[14] [14]
Rector TS, Bank AJ, Mullen KA, Tschumperlin LK, Sih R, Pillai K, Kubo SH. Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure. Circulation. 1996, 93 (12): 2135–41 [2006-09-25]. PMID 8925582. （原始内容存档于2011-06-08）.

[15] [15]
Ceremuzynski L, Chamiec T, Herbaczynska-Cedro K. Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris. Am J Cardiol. 1997, 80 (3): 331–3. PMID 9264427.

[JNutr2004-Loscalzo-16] [16]
Loscalzo J. L-arginine and atherothrombosis. J Nutr. 2004, 134 (10 Suppl): 2798S–2800S; discussion 2818S–2819S. PMID 15465788. （原始内容存档于2004-12-10）.

[VascMed2003-Janatuinen-17] [17]
Janatuinen T, Laakso J, Laaksonen R, Vesalainen R, Nuutila P, Lehtimaki T, Raitakari OT, Knuuti J. Plasma asymmetric dimethylarginine modifies the effect of pravastatin on myocardial blood flow in young adults. Vasc Med. 2003, 8 (3): 185–9. PMID 14989559.

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