Home Alteration of homocysteine catabolism in pre-eclampsia, HELLP syndrome and placental insufficiency
Article
Licensed
Unlicensed Requires Authentication

Alteration of homocysteine catabolism in pre-eclampsia, HELLP syndrome and placental insufficiency

  • Wolfgang Herrmann , Ulrich Hübner , Ines Koch , Rima Obeid , Ulrich Retzke and Jürgen Geisel
Published/Copyright: June 1, 2005

Abstract

Hyperhomocysteinemia is a risk factor in obstetrical complications such as pre-eclampsia, ‘hemolysis, elevated liver enzymes, low platelet’ (HELLP)-syndrome and placental insufficiency. The aim of our study was to investigate the alterations of homocysteine catabolism in these patients in relation to serum B-vitamins and renal function. Maternal fasting serum from preeclampsia (n = 24), HELLP (n = 20) and placental insufficiency (n = 25) patients at the time of diagnosis and pregnant controls (n = 34) was analyzed for homocysteine and its metabolites cystathionine and methylmalonic acid, the vitamins B6, B12 and folate, renal and additional parameters. Cystathionine, a parameter of homocysteine catabolism, was significantly increased in pre-eclampsia and HELLP compared with controls and placental insufficiency patients (mean concentrations: 343, 324, 248, 227 nmol/l; p=0.001). Homocysteine, folic acid, vitamin B6 and methylmalonic acid, however, did not differ significantly between groups. The main determinants of cystathionine are cystatin C and vitamin B6, whereas the main determinants of homocysteine are folate and uric acid. The strongest dependency of cystathionine on vitamin B6 was observed in pre-eclampsia and HELLP patients. The results suggest that the vitamin B6-dependent trans-sulfuration pathway is activated in pre-eclampsia and HELLP syndrome, probably by oxidative stress. Therefore, the demand for vitamin B6 is increased in these patients. Furthermore, renal dysfunction and low vitamin B6 levels contribute to the increase of cystathionine in pre-eclampsia and HELLP patients.

References

1 Hubel CA. Oxidative stress in the pathogenesis of pre-eclampsia. Proc Soc Exp Biol Med 1999; 222:222–35.10.1046/j.1525-1373.1999.d01-139.xSearch in Google Scholar

2 Krauss T, Emons G, Kuhn W, Augustin HG. Predictive value of routine circulating soluble endothelial cell adhesion molecule measurements during pregnancy. Clin Chem 2002; 48:1418–25.10.1093/clinchem/48.9.1418Search in Google Scholar

3 Johnson MR, Anim-Nyame N, Johnson P, Sooranna SR, Steer PJ. Does endothelial cell activation occur with intrauterine growth restriction? Br J Obstet Gynaecol 2002; 109:836–9.10.1111/j.1471-0528.2002.01045.xSearch in Google Scholar

4 Herrmann W. The importance of hyperhomocysteinemia as a risk factor for diseases: an overview. Clin Chem Lab Med 2001; 39:666–74.10.1515/CCLM.2001.110Search in Google Scholar

5 Stanger O, Weger M, Renner W, Konetschny R. Vascular dysfunction in hyperhomocyst(e)inemia. Implications for atherothrombotic disease. Clin Chem Lab Med 2001; 39:725–33.10.1515/CCLM.2001.121Search in Google Scholar

6 Yamamoto M, Hara H, Adachi T. Effects of homocysteine on the binding of extracellular-superoxide dismutase to the endothelial surface. FEBS Lett 2000; 486:159–62.10.1016/S0014-5793(00)02260-2Search in Google Scholar

7 Powers RW, Evans RW, Majors AK, Ojimba JI, Ness RB, Crombleholme WR, et al. Plasma homocysteine concentration is increased in pre-eclampsia and is associated with evidence of endothelial activation. Am J Obstet Gynecol 1998; 179:1605–11.10.1016/S0002-9378(98)70033-XSearch in Google Scholar

8 Leeda M, Riyazi N, de Vries JIP, Jakobs C, van Geijn HP, Dekker GA. Effects of folic acid and vitamin B6 supplementation on women with hyperhomocysteinemia and a history of pre-eclampsia or fetal growth restriction. Am J Obstet Gynecol 1998; 179:135–9.10.1016/S0002-9378(98)70263-7Search in Google Scholar

9 Rajkovic A, Mahomed K, Malinow MR, Sorensen TK, Woelk GB, Williams MA. Plasma homocyst(e)ine concentrations in eclamptic and pre-eclamptic African women postpartum. Obstet Gynecol 1999; 94:355–60.Search in Google Scholar

10 Wang J, Trudinger BJ, Duarte N, Wilcken DE, Wang XL. Elevated circulating homocyst(e)ine levels in placental vascular disease and associated pre-eclampsia. Br J Obstet Gynaecol 2000; 107:935–8.10.1111/j.1471-0528.2000.tb11095.xSearch in Google Scholar PubMed

11 Cotter A, Molloy AM, Scott JM, Daly SF. Elevated plasma homocysteine in early pregnancy: a risk factor for the development of severe pre-eclampsia. Am J Obstet Gynecol 2001; 185:781–5.10.1067/mob.2001.117304Search in Google Scholar PubMed

12 Murphy MM, Scott JM, McPartlin JM, Fernandez-Ballart JD. The pregnancy-related decrease in fasting plasma homocysteine is not explained by folic acid supplementation, hemodilution, or a decrease in albumin in a longitudinal study. Am J Clin Nutr 2002; 76:614–9.10.1093/ajcn/76.3.614Search in Google Scholar

13 Geisel J, Hübner U, Bodis M, Schorr H, Knapp JP, Obeid R, et al. The role of genetic factors in the development of hyperhomocysteinemia. Clin Chem Lab Med 2003; 41:1427–34.10.1515/CCLM.2003.219Search in Google Scholar

14 Cikot RJLM, Steegers-Theunissen RPM, Thomas CMG, De Boo TM, Merkus HMW, Steegers EAP. Longitudinal vitamin and homocysteine levels in normal pregnancy. Br J Nutr 2001; 85:49–58.10.1079/BJN2000209Search in Google Scholar

15 Herrmann W, Schorr H, Obeid R, Geisel J. Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomo-cysteinemia in vegetarians. Am J Clin Nutr 2003; 78:131–6.10.1093/ajcn/78.1.131Search in Google Scholar

16 Guttormsen AB, Ueland PM, Svarstad E, Refsum H. Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure. Kidney Int 1997; 52:495–502.10.1038/ki.1997.359Search in Google Scholar

17 Stabler SP, Marcell PD, Podell ER, Allen RH, Savage DG, Lindenbaum J. Elevation of total homocysteine in the serum of patients with cobalamin and folate deficiency detected by capillary gas chromatography-mass spectrometry. J Clin Invest 1988; 81:466–74.10.1172/JCI113343Search in Google Scholar

18 Mosharov E, Cranford MR, Banerjee J. The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes. Biochemistry 2000; 39:13005–11.10.1021/bi001088wSearch in Google Scholar

19 Taoka S, Lepore BW, Kabil Ö, Ojha S, Ringe D, Banerjee R. Human cystathionine β-synthase is a heme sensor protein. Evidence that the redox sensor is heme and not the vicinal cysteines in the CXXC motif seen in the crystal structure of the truncated enzyme. Biochemistry 2002; 42:10454–61.10.1021/bi026052dSearch in Google Scholar

20 Anim-Nyame N, Gamble J, Sooranna SR, Johnson MR, Steer PJ. Microvascular permeability is related to circulating levels of tumor necrosis factor-α in pre-eclampsia. Cardiovasc Res 2003; 58:162–9.10.1016/S0008-6363(02)00844-1Search in Google Scholar

21 Zou CG, Banerjee R. Tumor necrosis factor-α induced targeted proteolysis of cystathionine β-synthase modulates redox homeostasis. J Biol Chem 2003; 278:16802–8.10.1074/jbc.M212376200Search in Google Scholar PubMed

22 Malmezat T, Breuillé D, Pouyet C, Buffière C, Denis P, Mirand PP, et al. Methionine transsulfuration is increased during sepsis in rats. Am J Physiol Endocrinol Metab 2000; 279:E1391–7.10.1152/ajpendo.2000.279.6.E1391Search in Google Scholar

23 Sturman JA, Cohen PA, Gaull G. Effects of deficiency of vitamin B6 on transsulfuration. Biochem Med 1969; 3:244–5.10.1016/0006-2944(69)90023-4Search in Google Scholar

24 Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R, et al. The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J Clin Invest 1996; 98:177–84.10.1172/JCI118763Search in Google Scholar PubMed PubMed Central

25 Herrmann W, Schorr H, Geisel J, Riegel W. Homocysteine, cystathionine, methylmalonic acid and B-vitamins in patients with renal disease. Clin Chem Lab Med 2001; 39:739–46.10.1515/CCLM.2001.123Search in Google Scholar PubMed

26 Sorensen TK, Malinov MR, Williams MA, King IB, Luthy DA. Elevated second-trimester serum homocyst(e)ine levels and subsequent risk of pre-eclampsia. Gynecol Obstet Invest 1999; 48:98–103.10.1159/000010148Search in Google Scholar PubMed

27 Hogg B, Tamura T, Johnston KE, Dubard MB, Goldenberg RL. Second-trimester plasma homocysteine levels and pregnancy-induced hypertension, pre-eclampsia, and intrauterine growth restriction. Am J Obstet Gynecol 2000; 183:805–9.10.1067/mob.2000.109044Search in Google Scholar PubMed

28 Infante-Rivard C, Rivard GE, Gauthier R, Theoret Y. Unexpected relationship between plasma homocysteine and intrauterine growth restriction. Clin Chem 2003; 49:1476–82.10.1373/49.9.1476Search in Google Scholar PubMed

29 van Guldner C, Kulik W, Berger R, Dijkstra DA, Jakobs C, Reijngoud DJ, et al. Homocysteine and methionine metabolism in ESRD: a stable isotope study. Kidney Int 1999; 56:1064–71.10.1046/j.1523-1755.1999.00624.xSearch in Google Scholar PubMed

30 McCaddon A, Regland B, Hudson P, Davies G. Functional vitamin B12 deficiency and Alzheimer disease. Neurology 2002; 58:1395–9.10.1212/WNL.58.9.1395Search in Google Scholar

31 Conrad KP, Lindheimer MD. Renal and cardiovascular alterations. In: Lindheimer MD, Roberts JM, Cunningham FG, editors. Chesley’s hypertensive disorders in pregnancy. Stamford, CT: Appleton & Lange, 1999:263–326.Search in Google Scholar

32 Powers RW, Majors AK, Kerchner LJ, Conrad KP. Renal handling of homocysteine during normal pregnancy and pre-eclampsia. J Soc Gynecol Invest 2004; 11:45–50.10.1016/j.jsgi.2003.07.007Search in Google Scholar PubMed

33 Stead LM, Au KP, Jacobs RL, Brosnan M, Brosnan JT. Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. Am J Physiol Endocrinol Metabol 2001; 281:E1095–100.10.1152/ajpendo.2001.281.5.E1095Search in Google Scholar

34 Wachstein M, Graffeo LW. Influence of vitamin B6 on the incidence of pre-eclampsia. Obstet Gynecol 1956; 8:177–80.Search in Google Scholar

35 Chang SJ. Adequacy of maternal pyridoxine supplementation during pregnancy in relation to the vitamin B6 status and growth of neonates at birth. J Nutr Sci Vitaminol 1999; 45:499–558.10.3177/jnsv.45.449Search in Google Scholar

36 Schuster K, Bailey LB, Mahan CS. Effect of maternal pyridoxine HCl supplementation on the vitamin B6 status of mother and infant and on pregnancy outcome. J Nutr 1984; 114:977–88.10.1093/jn/114.5.977Search in Google Scholar

37 Holdsworth CD, Atkinson M, Dossett JA, Hall R. An assessment of the diagnostic and prognostic value of serum vitamin B12 levels in liver disease. Gut 1964; 5:601–6.10.1136/gut.5.6.601Search in Google Scholar

38 Hernández-Díaz S, Werler MM, Louik C, Mitchell AA. Risk of gestational hypertension to folic acid supplementation during pregnancy. Am J Epidemiol 2002; 156:806–12.10.1093/aje/kwf129Search in Google Scholar

39 Sanchez SE, Zhang C, Malinow MR, Ware-Jauregui S, Larrabure G, Williams MA. Plasma folate, vitamin B12, and homocyst(e)ine concentrations in pre-eclamptic and normotensive Peruvian women. Am J Epidemiol 2001; 153:474–80.10.1093/aje/153.5.474Search in Google Scholar

40 Ray JG, Mamdani MM. Association between folic acid food fortification and hypertension or pre-eclampsia in pregnancy. Arch Intern Med 2002; 162:1776–7.10.1001/archinte.162.15.1776Search in Google Scholar

41 Chappell LC, Seed PT, Briley AL, Kelly FJ, Lee R, Hunt BJ, et al. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial. Lancet 1999; 354:810–6.10.1016/S0140-6736(99)80010-5Search in Google Scholar

Received: 2004-4-8
Accepted: 2004-8-20
Published Online: 2005-6-1
Published in Print: 2004-10-1

© Walter de Gruyter

Articles in the same Issue

  1. The significance of serum γ-glutamyltransferase in cardiovascular diseases
  2. Anti-tissue transglutaminase antibodies in inflammatory bowel disease: new evidence
  3. Expression level of MDR1 message in peripheral blood leukocytes from healthy adults: a competitive nucleic acid sequence-based amplification assay for its determination
  4. Characteristics of prolinase against various iminodipeptides in erythrocyte lysates from a normal human and a patient with prolidase deficiency
  5. Alteration of homocysteine catabolism in pre-eclampsia, HELLP syndrome and placental insufficiency
  6. Immune system-mediated endothelial damage is associated with NO and antioxidant system disorders
  7. Bone marrow microvascular density and angiogenic growth factors in multiple myeloma
  8. The insulin-like growth factor system in the circulation of patients with viral infections
  9. Time course of systemic markers of inflammation in patients presenting with acute coronary syndromes
  10. Age- and sex-related reference values for serum insulin concentration and its biological determinants in a French healthy population. The STANISLAS cohort
  11. Potential pitfalls of comparative measurements of reticulocytes with flow cytometry and microscopy in prematures and infants
  12. Screening of antinuclear antibodies: comparison between enzyme immunoassay based on nuclear homogenates, purified or recombinant antigens and immunofluorescence assay
  13. Analytical and diagnostic accuracy of the EliA™ automated enzyme fluoroimmunoassay for antineutrophil cytoplasmic autoantibody detection
  14. A particle-enhanced turbidimetric immunoassay for quantitative determination of orosomucoid in urine: development, validation and reference values
  15. Analytical performance and clinical results of a fully automated MEIA system for brain natriuretic peptide assay: comparison with a point of care testing method
  16. Multicentre performance evaluation of the E170 Module for MODULAR ANALYTICS
  17. Congress of Clinical Chemistry and Laboratory Medicine Annual meeting of the German United Society for Clinical Chemistry and Laboratory Medicine (DGKL), Düsseldorf, Germany, November 22-24, 2004
Downloaded on 14.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/CCLM.2004.228/html
Scroll to top button