Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Định lượng nhiều loại phân tử trong huyết tương liên quan đến chuyển hóa một-carbon bằng phương pháp HPLC-MS/MS có khả năng thông lượng cao và tiêu tốn thể tích thấp
Tóm tắt
Nguy cơ mắc các bệnh mãn tính như bệnh tim mạch và ung thư đã được liên kết với các dấu hiệu sinh học liên quan đến chuyển hóa một-carbon, bao gồm một mạng lưới chuyển hóa với các con đường tương tác lẫn nhau. Để giải quyết sự phức tạp này trong các nghiên cứu dịch tễ học, chúng tôi đã thiết lập phương pháp HPLC-MS/MS pha loãng đồng vị để định lượng 12 dấu hiệu sinh học và các chuyển hóa. Tất cả quy trình xử lý mẫu đều được thực hiện bởi một hệ thống robot. Phép thử sử dụng 45 μL huyết tương, và việc xử lý mẫu bao gồm kết tủa protein bằng axit trichloroacetic. Các chất phân tích được tách trên cột Fortis Phenyl sử dụng pha di chuyển isocratic chứa nước, methanol và axit axetic. Methionine, methionine sulfoxide, choline, betaine, dimethylglycine, arginine, dimethylarginine đối xứng, dimethylarginine không đối xứng, homoarginine, creatinine, cystathionine và trimethyllysine đều cho thấy giới hạn phát hiện thấp hơn nhiều so với phân phối huyết tương của người khỏe mạnh ở phân vị thứ 5, hệ số biến thiên nằm trong khoảng 2.2-12.3 %, và tỷ lệ hồi phục đạt 80-131 %. Quy trình xử lý mẫu đơn giản, tiêu thụ thể tích thấp, khả năng phân tích nhiều ảnh hưởng và thời gian chạy ngắn của phương pháp này làm cho nó phù hợp cho việc định lượng chuyển hóa quy mô lớn từ các mẫu sinh học quý giá.
Từ khóa
#một-carbon #chuyển hóa #HPLC-MS/MS #dấu hiệu sinh học #định lượng nhiều loại #huyết tương #phương pháp phân tíchTài liệu tham khảo
Smulders YM, Blom HJ (2011) The homocysteine controversy. J Inherit Metab Dis 34(1):93–99. doi:10.1007/s10545-010-9151-1
Ueland PM (2011) Choline and betaine in health and disease. J Inherit Metab Dis 34(1):3–15. doi:10.1007/s10545-010-9088-4
Duthie SJ (2011) Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis. J Inherit Metab Dis 34(1):101–109. doi:10.1007/s10545-010-9128-0
Mangoni AA (2009) The emerging role of symmetric dimethylarginine in vascular disease. Adv Clin Chem 48:73–94
Finkelstein JD (1990) Methionine metabolism in mammals. J Nutr Biochem 1:228–237
Teerlink T (2005) ADMA metabolism and clearance. Vasc Med 10(Suppl 1):S73–S81
Tran CT, Leiper JM, Vallance P (2003) The DDAH/ADMA/NOS pathway. Atheroscler Suppl 4(4):33–40
Brosnan JT, Brosnan ME (2007) Creatine: endogenous metabolite, dietary, and therapeutic supplement. Annu Rev Nutr 27:241–261. doi:10.1146/annurev.nutr.27.061406.093621
Konstantinova SV, Tell GS, Vollset SE, Nygard O, Bleie O, Ueland PM (2008) Divergent associations of plasma choline and betaine with components of metabolic syndrome in middle age and elderly men and women. J Nutr 138(5):914–920
Moali C, Boucher JL, Sari MA, Stuehr DJ, Mansuy D (1998) Substrate specificity of NO synthases: detailed comparison of L-arginine, homo-L-arginine, their N omega-hydroxy derivatives, and N omega-hydroxynor-L-arginine. Biochemistry 37(29):10453–10460. doi:10.1021/bi980742tbi980742t
Moncada S, Higgs A (1993) The L-arginine-nitric oxide pathway. N Engl J Med 329(27):2002–2012. doi:10.1056/NEJM199312303292706
Cooke JP (2004) Asymmetrical dimethylarginine: the Uber marker. Circulation 109(15):1813–1818. doi:10.1161/01.CIR.0000126823.07732.D5
Bode-Boger SM, Scalera F, Kielstein JT, Martens-Lobenhoffer J, Breithardt G, Fobker M, Reinecke H (2006) Symmetrical dimethylarginine: a new combined parameter for renal function and extent of coronary artery disease. J Am Soc Nephrol 17(4):1128–1134. doi:10.1681/ASN.2005101119
Fliser D, Kronenberg F, Kielstein JT, Morath C, Bode-Boger SM, Haller H, Ritz E (2005) Asymmetric dimethylarginine and progression of chronic kidney disease: the mild to moderate kidney disease study. J Am Soc Nephrol 16(8):2456–2461. doi:10.1681/ASN.2005020179
Meinitzer A, Kielstein JT, Pilz S, Drechsler C, Ritz E, Boehm BO, Winkelmann BR, Marz W (2011) Symmetrical and asymmetrical dimethylarginine as predictors for mortality in patients referred for coronary angiography: the Ludwigshafen Risk and Cardiovascular Health study. Clin Chem 57(1):112–121. doi:10.1373/clinchem.2010.150854
Marz W, Meinitzer A, Drechsler C, Pilz S, Krane V, Kleber ME, Fischer J, Winkelmann BR, Bohm BO, Ritz E, Wanner C (2010) Homoarginine, cardiovascular risk, and mortality. Circulation 122(10):967–975. doi:10.1161/CIRCULATIONAHA.109.908988
Kielstein JT, Veldink H, Martens-Lobenhoffer J, Haller H, Burg M, Lorenzen JM, Lichtinghagen R, Bode-Boger SM, Kliem V (2011) SDMA is an early marker of change in GFR after living-related kidney donation. Nephrol Dial Transplant 26(1):324–328. doi:10.1093/ndt/gfq395
Mashima R, Nakanishi-Ueda T, Yamamoto Y (2003) Simultaneous determination of methionine sulfoxide and methionine in blood plasma using gas chromatography–mass spectrometry. Anal Biochem 313(1):28–33
Holm PI, Ueland PM, Kvalheim G, Lien EA (2003) Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry. Clin Chem 49(2):286–294
Kirsch SH, Herrmann W, Rabagny Y, Obeid R (2010) Quantification of acetylcholine, choline, betaine, and dimethylglycine in human plasma and urine using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 878(32):3338–3344. doi:10.1016/j.jchromb.2010.10.016
Teerlink T (2007) HPLC analysis of ADMA and other methylated L-arginine analogs in biological fluids. J Chromatogr B Analyt Technol Biomed Life Sci 851(1–2):21–29. doi:10.1016/j.jchromb.2006.07.024
Blackwell S, O’Reilly DS, Talwar D (2007) Biological variation of asymmetric dimethylarginine and related arginine metabolites and analytical performance goals for their measurement in human plasma. Eur J Clin Invest 37(5):364–371. doi:10.1111/j.1365-2362.2007.01798.x
Blackwell S, O’Reilly DS, Talwar DK (2009) HPLC analysis of asymmetric dimethylarginine (ADMA) and related arginine metabolites in human plasma using a novel non-endogenous internal standard. Clin Chim Acta 401(1–2):14–19. doi:10.1016/j.cca.2008.10.032
Jones CE, Darcy CJ, Woodberry T, Anstey NM, McNeil YR (2010) HPLC analysis of asymmetric dimethylarginine, symmetric dimethylarginine, homoarginine and arginine in small plasma volumes using a Gemini-NX column at high pH. J Chromatogr B Analyt Technol Biomed Life Sci 878(1):8–12. doi:10.1016/j.jchromb.2009.10.035
Marra M, Bonfigli AR, Testa R, Testa I, Gambini A, Coppa G (2003) High-performance liquid chromatographic assay of asymmetric dimethylarginine, symmetric dimethylarginine, and arginine in human plasma by derivatization with naphthalene-2,3-dicarboxaldehyde. Anal Biochem 318(1):13–17
Teerlink T, Nijveldt RJ, de Jong S, van Leeuwen PA (2002) Determination of arginine, asymmetric dimethylarginine, and symmetric dimethylarginine in human plasma and other biological samples by high-performance liquid chromatography. Anal Biochem 303(2):131–137. doi:10.1006/abio.2001.5575S0003269701955757
Meinitzer A, Puchinger M, Winklhofer-Roob BM, Rock E, Ribalta J, Roob JM, Sundl I, Halwachs-Baumann G, Marz W (2007) Reference values for plasma concentrations of asymmetrical dimethylarginine (ADMA) and other arginine metabolites in men after validation of a chromatographic method. Clin Chim Acta 384(1–2):141–148. doi:10.1016/j.cca.2007.07.006
Weaving G, Rocks BF, Bailey MP, Titheradge MA (2008) Arginine and methylated arginines in human plasma and urine measured by tandem mass spectrometry without the need for chromatography or sample derivatisation. J Chromatogr B Analyt Technol Biomed Life Sci 874(1–2):27–32. doi:10.1016/j.jchromb.2008.08.016
Huang LF, Guo FQ, Liang YZ, Li BY, Cheng BM (2004) Simultaneous determination of L-arginine and its mono- and dimethylated metabolites in human plasma by high-performance liquid chromatography-mass spectrometry. Anal Bioanal Chem 380(4):643–649. doi:10.1007/s00216-004-2759-y
El-Khoury JM, Bunch DR, Reineks E, Jackson R, Steinle R, Wang S (2012) A simple and fast liquid chromatography-tandem mass spectrometry method for measurement of underivatized L-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges. Anal Bioanal Chem 402(2):771–779. doi:10.1007/s00216-011-5462-9
Davids M, Swieringa E, Palm F, Smith DE, Smulders YM, Scheffer PG, Blom HJ, Teerlink T (2012) Simultaneous determination of asymmetric and symmetric dimethylarginine, l-monomethylarginine, l-arginine, and l-homoarginine in biological samples using stable isotope dilution liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 900:38–47. doi:10.1016/j.jchromb.2012.05.025
Ueland PM, Midttun O, Windelberg A, Svardal A, Skalevik R, Hustad S (2007) Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry. Clin Chem Lab Med 45(12):1737–1745. doi:10.1515/CCLM.2007.339
Blanchard J (1981) Evaluation of the relative efficacy of various techniques for deproteinizing plasma samples prior to high-performance liquid chromatographic analysis. J Chromatogr 226(2):455–460
Hustad S, Eussen S, Midttun O, Ulvik A, van de Kant PM, Morkrid L, Gislefoss R, Ueland PM (2012) Kinetic modeling of storage effects on biomarkers related to B vitamin status and one-carbon metabolism. Clin Chem 58(2):402–410. doi:10.1373/clinchem.2011.174490
Yue B, Pattison E, Roberts WL, Rockwood AL, Danne O, Lueders C, Mockel M (2008) Choline in whole blood and plasma: sample preparation and stability. Clin Chem 54(3):590–593. doi:10.1373/clinchem.2007.094201
Midttun O, Hustad S, Ueland PM (2009) Quantitative profiling of biomarkers related to B-vitamin status, tryptophan metabolism and inflammation in human plasma by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 23:1371–1379
Tsikas D, Wolf A, Mitschke A, Gutzki FM, Will W, Bader M (2010) GC-MS determination of creatinine in human biological fluids as pentafluorobenzyl derivative in clinical studies and biomonitoring: inter-laboratory comparison in urine with Jaffe, HPLC and enzymatic assays. J Chromatogr B Analyt Technol Biomed Life Sci 878(27):2582–2592. doi:10.1016/j.jchromb.2010.04.025
Marchi I, Viette V, Badoud F, Fathi M, Saugy M, Rudaz S, Veuthey JL (2010) Characterization and classification of matrix effects in biological samples analyses. J Chromatogr A 1217(25):4071–4078. doi:10.1016/j.chroma.2009.08.061
Melnyk S, Pogribna M, Pogribny I, Hine RJ, James SJ (1999) A new HPLC method for the simultaneous determination of oxidized and reduced plasma aminothiols using coulometric electrochemical detection. J Nutr Biochem 10(8):490–497
Sigit JI, Hages M, Brensing KA, Frotscher U, Pietrzik K, von Bergmann K, Lutjohann D (2001) Total plasma homocysteine and related amino acids in end-stage renal disease (ESRD) patients measured by gas chromatography–mass spectrometry–comparison with the Abbott IMx homocysteine assay and the HPLC method. Clin Chem Lab Med 39(8):681–690
Atzler D, Mieth M, Maas R, Bøger RH, Schwedhelm E (2011) Stable isotope dilution assay for liquid chromatography–tandem mass spectrometric determination of l-homoarginine in human plasma. J Chromatogr B 879:2294–2298
Midttun O, Hustad S, Schneede J, Grotmol T, Hoff G, Ueland P (2007) Plasma vitamin B6 forms and their relations to transsulfuration metabolites in a large-scale population-based study. Am J Clin Nutr 86:131–138
Allen RH, Stabler SP, Savage DG, Lindenbaum J (1993) Metabolic abnormalities in cobalamin (vitamin B12) and folate deficiency. FASEB J 7(14):1344–1353
Holm PI, Ueland PM, Vollset SE, Midttun O, Blom HJ, Keijzer MB, den Heijer M (2005) Betaine and folate status as cooperative determinants of plasma homocysteine in humans. Arterioscler Thromb Vasc Biol 25(2):379–385
Windelberg A, Arseth O, Kvalheim G, Ueland PM (2005) Automated assay for the determination of methylmalonic acid, total homocysteine, and related amino acids in human serum or plasma by means of methylchloroformate derivatization and gas chromatography–mass spectrometry. Clin Chem 51(11):2103–2109
Ringseis R, Hanisch N, Seliger G, Eder K (2010) Low availability of carnitine precursors as a possible reason for the diminished plasma carnitine concentrations in pregnant women. BMC Pregnancy Childbirth 10:17. doi:10.1186/1471-2393-10-17