Clinical diagnostics for homocysteine: A rogue amino acid?

Expert Review of Molecular Diagnostics

Volumn 10, Issue 4, 2010, Pages 489-500

  Newton, Laura A A ^a   Sandhu, Kiran ^a   Livingstone, Callum ^b   Leslie, Ray ^a   Davis, James ^c  

^a NOTTINGHAM TRENT UNIVERSITY   (United Kingdom)

^b ROYAL SURREY COUNTY HOSPITAL   (United Kingdom)

^c UNIVERSITY OF ULSTER   (United Kingdom)

Author keywords

Analysis; Biomarker; Detection; Heart disease; Homocysteine

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); BIOLOGICAL MARKER; CYANOCOBALAMIN; FOLIC ACID; HOMOCYSTEINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NITRIC OXIDE; PYRIDOXINE; TRIPHENYLPHOSPHINE; VITAMIN B GROUP;

AGE DISTRIBUTION; AMINO ACID BLOOD LEVEL; AMINO ACID METABOLISM; AMINO ACID SYNTHESIS; CAPILLARY ELECTROPHORESIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CYANOCOBALAMIN DEFICIENCY; DEGENERATIVE DISEASE; DIAGNOSTIC VALUE; DIETARY INTAKE; DISEASE MARKER; FOLIC ACID DEFICIENCY; GAS CHROMATOGRAPHY; GENETIC DISORDER; HEREDITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HYPERHOMOCYSTEINEMIA; LIFESTYLE; MASS FRAGMENTOGRAPHY; MENTAL DISEASE; NEUROLOGIC DISEASE; NONHUMAN; OSTEOPOROSIS; PATHOPHYSIOLOGY; PREGNANCY COMPLICATION; PROTEIN STRUCTURE; PYRIDOXINE DEFICIENCY; REVIEW; SEX DIFFERENCE; VITAMIN DEFICIENCY;

EID: 77952522155     PISSN: 14737159     EISSN: 17448352     Source Type: Journal    
DOI: 10.1586/erm.10.19     Document Type: Review

References (98)

1. White PC, Lawrence NS, Davis J, Compton RG. Electrochemically initiated 1, 4 additions: a versatile route to the determination of thiols. Anal. Chim. Acta 447 (1-2), 1-10 (2001).
2. Netto L E S, Oliveira M A D, Monteiro G et al. Reactive cysteine in proteins: protein folding, antioxidant defense, redox signaling and more. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 146 (1-2), 180-193 (2007).
3. Christopher S N G, Stevan BS. Contemporary management of Cystinuria. J. Endourol. 13 (9), 647 (2009).
4. Zuofeng C, Yanbing Z. Electrochemical recognition of single-methylene difference between cysteine and homocysteine. J. Electroanal. Chem. 624 (1-2), 9-13 (2008).
5. Humphrey LH, Fu R, Rogers K, Freeman M, Helfard M. Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis. Mayo Clin. Proc. 83, 1203-1212 (2008).
6. Martignoni E, Tassorelli C, Nappi G, Zangaglia R, Pacchetti C, Blandini F. Homocysteine and Parkinson's disease: a dangerous liaison? J. Neurol. Sci. 257, 31-37 (2007).
7. Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett. 580, 2994-3005 (2006).
8. Babiloni C, Bosco P, Ghidoni R et al. Homocysteine and electroencephalographic rhythms in Alzheimer disease: a multicentric study. Neuroscience 145, 942-954 (2007).
9. Cacciapuoti G, Manna C, Napoli D, Zappia V, Porcelli M. Homocysteineinduced endothelial cell adhesion is related to adenosine lowering and is not mediated by S-adenosylhomocysteine. FEBS Lett. 581, 4567-4570 (2007).
10. Stühlinger MC, Oka RK, Graf EE et al. Endothelial dysfunction induced by hyperhomocyst (e) inemia: role of asymmetric dimethylarginine. Circulation 933-938 (2003).
11. Luo F, Liu X, Wang S, Chen H. Effect of homocysteine on platelet activation induced by collagen. Nutrition 22, 69-75 (2006).
12. Tsai J, Perrella MA, Yoshimizumi M et al. Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. Proc. Natl Acad. Sci. USA 91, 6369-6373 (1994).
13. Buemi M, Marino D, Di Pasquale G et al. Effects of homocysteine on proliferation, necrosis, and apoptosis of vascular smooth muscle cells in culture and influence of folic acid. Thromb. Res. 104, 207-213 (2001).
14. Refsum H, Smith AD, Ueland PM et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin. Chem. 50, 3-32 (2004). Interesting article looking at all of the factors that can affect plasma homocysteine concentrations. This includes looking at different medical conditions, which are discussed in this article, but also looks at the other risk factors that we did not consider.
15. The Homocysteine Studies Collaboration. Homocysteine studies collaboration, Homocysteine and risk of ischemic heart disease and stroke: a meta analysis. JAMA 288 (16), 2015-2022 (2002).
16. 6 exert distinct effects on homocysteine, serine, and methionine kinetics. Am. J. Physiol. Endocrinol. Metab. 281, E1182-E1190 (2001).
17. Assies J, Lok A, Bockting CL et al. Fatty acids and homocysteine levels in patients with recurrent depression: an explorative pilot study. Prostaglandins Leukot. Essent. Fatty Acids 70, 349-356 (2004).
18. Holmes VA. Changes in haemostasis during normal pregnancy: does homocysteine play a role in maintaining homeostasis? Proc. Nutr. Soc. 62, 479-793 (2003).
19. Yazdanpanah N, Zillikens MC, Rivadeneira F et al. Effect of dietary B vitamins on BMD and risk of fracture in elderly men and women: the Rotterdam Study, Bone 41, 987-994 (2007).
20. Alley RA, Chen EL, Beyer TD, Prinz RA, Does homocysteine contribute to bone disease in hyperparathyroidism? Am. J. Surg. 195, 374-378 (2008).
21. Lubec B, Fang-Kircher S, Lubec T, Blom HJ, Boers G H J. Evidence for McKusick's hypothesis of deficient collagen crosslinking in patients with homocystinuria. Biochim. Biophys. Acta 1315, 159-162 (1996).
22. Diaz R. Update on the relationship between homocysteine, B-vitamins, and one-carbon metabolism in aging and neurodegenerative disease. Alzheimers Dement. 4, T200-T201 (2008).
23. Marcucci R, Zanazzi M, Bertoni E et al. Homocysteine-lowering therapy and carotid intima-media thickness in renal transplant recipients. Transplant. Proc. 37, 2491-2492 (2005).
24. Lim H, Cha Y, Chove R. Dietary intervention with emphasis on folate intake reduces serum lipids but not plasma homocysteine levels in hyperlipidemic patients. Nutr. Res. 28, 767-774 (2008).
25. Nekrassova O, Lawrence NS, Compton RG. Analytical determination of homocysteine: a review. Talanta 60, 1085-1095 (2003).
26. Jacobsen DW. Homocysteine and vitamins in cardiovascular disease. Clin. Chem. 44, 1833-1843 (1998).
27. Kuan Y, Dear AE, Grigg MJ. Homocysteine: an aetiological contributore to peripheral vascular arterial disease. ANZ J. Surg. 72, 688-671 (2002).
28. Hague WM. Homocysteine and pregnancy. Best Pract. Res. Clin. Obstet. Gynaecol. 17, 459-469 (2003).
29. De la Calle M, Usandizaga R, Sancha M, Magdaleno F, Herranz A, Cabrillo E. Homocysteine, folic acid and B-group vitamins in obstetrics and gynaecology. Eur. J. Obstet. Gynecol. Reprod. Biol. 107, 125-134 (2003).
30. Kaul S, Zadeh AA, Shah PK. Homocysteine hypothesis for atherothrombotic cardiovascular disease. J. Am. Coll. Cardiol. 48, 914-923 (2006).
31. Wickramasighe SN. Diagnosis in megaloblastic anaemias. Blood Rev. 20, 299-318 (2006).
32. 12 defciency. J. Nutr. 126, 1266S-1272S (1996).
33. 12 and folate deficiency in older persons. Am. J. Clin. Nutr. 77, 1241-1247 (2003).
34. Williams HM, Lippok H, Doherty GH. Nitric oxide and peroxynitrite signalling triggers homocysteine mediated apoptosis in trigeminal sensory neurons in vitro. Neurosci. Res. 60, 380-388 (2008).
35. Ventura P, Panini R, Tremosini S, Salvioli G. A role for homocysteine increase in haemolysis of megaloblastic anaemias due to vitamin B12 and folate deficiency: results from an in vitro experience. Biochim. Biophys. Acta 1739, 33-42 (2004).
36. Schorah GJ, Devitt H, Lucock M, Dowell AC, The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study. Eur. J. Clin. Nutr. 52, 407-411 (1998).
37. Sakamoto W, Isomura H, Fujie K et al. Homocysteine attenuates the expression of osteocalcin but enhances osteopontin in MC3T3-E1 preosteoblastic cells. Biochim. Biophys. Acta 1740, 12-16 (2005).
38. Lipton SA, Kim W, Choi Y et al. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-daspartate receptor. Proc. Natl Acad. Sci. USA 94, 5923-5928 (1997).
39. Zieminska E, Stafej A, Lazarewicz, JW. Role of group I metabotropic glutamate receptors and NMDA receptors in homocysteine-evoked acute neurodegeneration of cultured cerebellar granule neurones. Neurochem. Int. 43, 481-492 (2003).
40. Algaidi SA, Christie LA, Jenkinson AM, Whalley L, Riedel G, Platt B. Long-term homocysteine exposure induces alterations in spatial learning, hippocampal signalling and synaptic plasticity. Exp. Neurol. 197, 8-21 (2006).
41. Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci. 26, 137-146 (2003).
42. Haidemenos A, Kontis D, Gazi A, Kallai E, Allin M, Lucia B. Plasma homocysteine, folate and B12 in chronic schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry 31, 1289-1296 (2007).
43. Gurbuz A, Karateke A, Mengulluoglu M. Elevated plasma homocysteine levels in preeclampsia and eclampsia. Int. J. Gynecol. Obstet. 87, 165-166 (2004).
44. Zhang H, Luo G, Liang Q, Wang Y et al. Neural tube defects and disturbed maternal folate- and homocysteine-mediated one-carbon metabolism. Exp. Neurol. 212, 515-521 (2008).
45. Oakley P Jr. Elimination of folic acidpreventable neural tube defects. Am. J. Prevent. Med. 35, 606-607 (2008).
46. Ellison J, Clark P, Walker ID, Greer IA. Effect of supplementation with folic acid throughout pregnancy on plasma homocysteine concentration. Thromb. Res. 114, 25-27 (2004).
47. Hutchinson S, Aplinn RT, Webb H et al. Molecular effects of homocysteine on cdEGF domain structure: insights into the pathogenesis of homocysteinuria. J. Mol. Biol. 346, 833-844 (2005).
48. Lawson-Yuen A, Levy HL, The use of betaine in the treatment of elevated homocysteine. Mol. Genet. Metab. 88, 201-207 (2006).
49. Yap S, Boers G H J, Wilcken B et al. Vascular outcome in patients with homocystinuria due to cystathionine β-synthase deficiency treated chronically: a multicenter observational study. Arterioscler. Thromb. Vasc. Biol. 21, 2080-2085 (2001).
50. Naughten ER, Yap S, Mayne PD. Newborn screening for homocystinuria: Irish and world experience. Eur. J. Pediatr. 157 (2), S84-S87 (1998).
51. Buysschaert M, Gala JL, Bessomo A, Hermans MP. C677T methylenetetrahydrofolate reductase mutation in Type 2 diabetic patients with and without hyperhomocysteinaemia. Diabet. Metab. 30, 349-354 (2004).
52. Todorovic, Z, Džoljic E, Novakovic I et al. Homocysteine serum levels and MTHFR C677T genotype in patients with Parkinson's disease, with and without levodopa therapy. J. Neurol. Sci. 248, 56-61 (2006).
53. Martin-Herrero F, Jiménez-Candil J, Martín-Moreiras J et al. Homocysteine, cause or consequence? Int. J. Cardiol. 129, 276-277 (2008).
54. Rasmussen K, Moller L. Total homocysteine measurement in clinical practice. Ann. Clin. Biochem. 37, 627-648 (2000).
55. Hansen RE, Winther JR. An introduction to methods for analyzing thiols and disulfides: reactions, reagents, and practical considerations. Anal. Biochem. 394 (2), 147-158 (2009). Provides a comprehensive outline of the difficulties involved in the derivatization and selective detection of a broad range different thiol species, including homocysteine.
56. Chwatko G, Bald E. Determination of different species of homocysteine in human plasma by high-performance liquid chromatography with ultraviolet detection. J. Chromatogr. A 949 (1-2), 141-151 (2002).
57. Tcherkas YV, Denisenko AD. Simultaneous determination of several amino acids, including homocysteine, cysteine and glutamic acid, in human plasma by isocratic reversed-phase high-performance liquid chromatography with fluorimetric detection. J. Chromatogr. A 913 (1-2), 309-313 (2001).
58. Chou S, Ko L, Yang C. High performance liquid chromatography with fluorimetric detection for the determination of total homocysteine in human plasma: method and clinical applications. Anal. Chim. Acta 429 (2), 331-336 (2001).
59. Ducros, V, Schmitt D, Pernod G, Faure H, Polack B, Favier A. Gas chromatographic-mass spectrometric determination of total homocysteine in human plasma by stable isotope dilution: method and clinical applications. J. Chromatogr. B 729 (1-2), 333-339 (1999).
60. Myung S, Kim M, Min H, Yoo E, Kim K. Determination of homocysteine and its related compounds by solid-phase microextraction-gas chromatography-mass spectrometry. J. Chromatogr. B 727 (1-2), 1-8 (1999).
61. Ivanov AR, Nazimov IV, Baratova, L. Determination of biologically active low-molecular-mass thiols in human blood: I. Fast qualitative and quantitative, gradient and isocratic reversed-phase high-performance liquid chromatography with photometric and fluorescence detection. J. Chromatogr. A 895 (1-2), 157-166 (2000).
62. Caussé E, Issac C, Malatray P et al. Assays for total homocysteine and other thiols by capillary electrophoresis-laser-induced fluorescence detection: I. Preanalytical condition studies. J. Chromatogr. A 895 (1-2), 173-178 (2000).
63. Bald E, Kaniowska E, Chwatko G, Glowacki R. Liquid chromatographic assessment of total and protein-bound homocysteine in human plasma. Talanta 50 (6), 1233-1243 (2000).
64. Mukai Y, Togawa T, Suzuki T, Ohata, K, Tanabe S. Determination of homocysteine thiolactone and homocysteine in cell cultures using high-performance liquid chromatography with fluorescence detection. J. Chromatogr. B 767 (2), 263-268 (2002).
65. Minniti G, Piana A, Armani U, Cerone R. Determination of plasma and serum homocysteine by high-performance liquid chromatography with fluorescence detection. J. Chromatogr. A 828 (1-2), 401-405 (1998).
66. Chassaing C, Gonin J, Wilcox CS, Wainer IW. Determination of reduced and oxidized homocysteine and related thiols in plasma by thiol-specific pre-column derivatization and capillary electrophoresis with laser-induced fuorescence detection. J. Chromatogr. B 735, 219-227 (1999).
67. Amarnath K, Amarnath, Valentine HL, Valentine WM. A specific HPLC-UV method for the determination of cysteine and related aminothiols in biological samples. Talanta 60 (6), 1229-1238 (2003).
68. Nolin TD, McMenamin ME, Himmelfarb J. Simultaneous determination of total homocysteine, cysteine, cysteinylglycine, and glutathione in human plasma by highperformance liquid chromatography: application to studies of oxidative stress. J. Chromatogr. B 852, 554-561 (2007).
69. Zhang G, Liu D, Shuang S, Choi, M M F. A homocysteine biosensor with eggshell membrane as an enzyme immobilization platform. Sens. Actuators B Chem. 114 (2), 936-942 (2006).
70. Accinni R, Bartesaghi S, De Leo G et al. Screening of homocysteine from newborn blood spots by high-performance liquid chromatography with coulometric array detection. J. Chromatogr. A 896 (1-2), 183-189 (2000).
71. Agüí L, Peña-Farfal C, Yáñez-Sedeño P, Pingarrón JM. Electrochemical determination of homocysteine at a gold nanoparticle-modified electrode. Talanta 74 (3), 412-420 (2007).
72. Gong K, Dong Y, Xiong S, Chen Y, Mao L. Novel electrochemical method for sensitive determination of homocysteine with carbon nanotube-based electrodes. Biosens. Bioelect. 20 (2), 253-259 (2004).
73. Chen Z, Zu Y. Electrochemical recognition of single-methylene difference between cysteine and homocysteine. J. Electroanal. Chem. 624 (1-2), 9-13 (2008).
74. Cataldi T R I, Nardiello D. A pulsed potential waveform displaying enhanced detection capabilities towards sulfurcontaining compounds at a gold working electrode. J. Chromatogr. A 1066 (1-2), 133-142 (2005).
75. Jandik P, Cheng J, Evrovski J, Avdalovic N. Simultaneous analysis of homocysteine and methionine in plasma. J. Chromatogr. B 759 (1), 145-151 (2001).
76. Lawrence NS, Deo RP, Wang J. Detection of homocysteine at carbon nanotube paste electrodes. Talanta 63 (2), 443-449 (2004).
77. Windelberg A, Årseth O, Kvalheim G, Uelandclin PM. 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, 2103-2109 (2005).
78. Gempel K, Gerbitz K, Casetta B, Bauer MF. Rapid determination of total homocysteine in blood spots by liquid chromatography-electrospray ionization-tandem mass spectrometry. Clin. Chem. 46, 122-123 (2000).
79. Guan X, Hoffman B, Dwivedi C, Matthees DP. A simultaneous liquid chromatography/mass spectrometric assay of glutathione, cysteine, homocysteine and their disulfides in biological samples. J. Pharm. Biomed. Anal. 31 (2), 251-261 (2003).
80. Kuhn J, Götting C, Kleesiek K. Rapid micro-scale assay for homocysteine by liquid chromatography-tandem mass spectrometry. Clin. Biochem. 39 (2), 164-166 (2006).
81. Li S, Jia J, Liu G, Wang W, Cai Y, Wang Y, Yu C. Improved and simplified LC-ESI-MS/MS method for homocysteine determination in human plasma: application to the study of cardiovascular diseases. J. Chromatogr. B 870 (1), 63-67 (2008).
82. Glowacki R, Bald E. Fully automated method for simultaneous determination of total cysteine, cysteinylglycine, glutathione and homocysteinein plasma by HPLC with UV absorbance detection. J. Chromatogr. B 877 (28), 3400-3404 (2009).
83. Chen W, Zhao Y, Seefeldt T, Guan X. Determination of thiols and disulfides via HPLC quantification of 5-thio-2-nitrobenzoic acid. J. Pharm. Biomed. Anal. 48 (5), 1375-1380 (2008).
84. Ricci F, Arduini F, Amine A, Moscone D, Palleschi G. Characterisation of Prussian blue modified screen-printed electrodes for thiol detection. J. Electroanal. Chem. 563 (2), 229-237 (2004).
85. Ducros V, Demuth K, Sauvant M et al. Methods for homocysteine analysis and biological relevance of the results. J. Chromatogr. B 781, 207-226 (2002).
86. Caussé E, Siri N, Bellet H et al. Plasma homocysteine determined by capillary electrophoresis with laser-induced fluorescence detection. Clin. Chem. 45, 412-414 (1999).
87. Kang SH, Wei W, Yeung ES. On-column derivatization for the analysis of homocysteine and other thiols by capillary electrophoresis with laser-induced fluorescence detection. J. Chromatogr. B 744 (1), 149-156 (2000).
88. Duarte NL, Wang XL, Wilcken D E L. Effects of anticoagulant and time of plasma separation on measurement of homocysteine. Clin. Chem. 48, 665-668 (2002).
89. Demuth K, Ducros V, Michelsohn S, Paul J. Evaluation of Advia Centaur® automated chemiluminescence immunoassay for determining total homocysteine in plasma. Clin. Chim. Acta 349, 113-120 (2004).
90. Yu HH, Joubran R, Asmi M et al. Agreement among four homocysteine assays and results in patients with coronary atherosclerosis and controls. Clin. Chem. 46, 258-264 (2000).
91. Shipchandler MT, Moore EG. Rapid, fully automated measurement of plasma homocyst (e) ine with the Abbott lMx Analyzer. Clin. Chem. 41, 991-994 (1995).
92. Pernet P, Cuzon G, Lim SK, Labau N, Laghzal AC, Vaubourdolle M. Plasma homocysteine measurement with ion exchange chromatography (Jeol Aminotac 500): a comparison with the Abbott IMx assay. Med. Principles Pract. 15, 149-152 (2006).
93. Zappacosta B, Persichilli S, Minucci A et al. Evaluation of a new enzymatic method for homocysteine measurement. Clin. Biochem. 39, 62-66 (2006). Presents an overview a commercially available homocysteine analyzer that has provided a more suitable means of homocysteine analysis than the more conventional laboratory methods used, offering a more rapid and cost-effective means of analysis. This article highlights the technological advances in homocysteine analysis.
94. Roberts RF, Roberts WL. Performance characteristics of a recombinant enzymatic cycling assay for quantification of total homocysteine in serum or plasma. Clin. Chim. Acta 344 (1-2), 95-99 (2004).
95. Haltmayer M, Mueller T, Gegenhuber A, Poelz W. Comparison of the automated AxSYM and ADVIA centaur immunoassays for homocysteine determination. Clin. Lab. 50, 175-180 (2004).
96. Wood D, Wray R, Poulter N et al. JBS 2: Joint British Societies Guidelines on prevention of cardiovascular disease in clinical practice. Heart 91 (Suppl. 5), 1-52 (2005).
97. Malinow MR, Bostom AG, Krauss RM Homocysteine, diet and cardiovascular diseases: a statement for healthcare professionals from the nutrition committee, American Heart Association. Circulation 99, 178-182 (1999).
98. Bradley A, Maron MD, Loscalzo J. The treatment of hyperhomocysteinaemia. Ann. Rev. Med. 60, 39-54 (2009).