Startseite Hyperhomocysteinemia and macromolecule modifications in uremic patients
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Hyperhomocysteinemia and macromolecule modifications in uremic patients

  • Alessandra F. Perna , Rosanna Capasso , Cinzia Lombardi , Filomena Acanfora , Ersilia Satta und Diego Ingrosso
Veröffentlicht/Copyright: 21. September 2011
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 43 Heft 10

Abstract

Hyperhomocysteinemia is present in the majority of well-nourished chronic renal failure and uremic patients. Most observations reported in the literature come from studies carried out in end-stage renal disease patients treated with hemodialysis. The underlying mechanisms of the toxic effects of homocysteine in uremia related to cardiovascular disease and other disturbances are still under scrutiny. As a consequence, macromolecules (i.e., proteins and DNA) have been found to be altered to various extents. One of the mechanisms of homocysteine toxicity is related to the action of its metabolic precursor, S-adenosylhomocysteine, a powerful methyltransferase competitive inhibitor. Disruption of DNA methylation has been demonstrated to occur as a result of hyperhomocysteinemia, and/or is associated with vascular damage. DNA hypomethylation has been found in the mononuclear cell fraction of uremic patients with hyperhomocysteinemia. Proteins are also targets of homocysteine-dependent molecular damage. The formation of oxidative products with free cysteinyl residue thiol groups has been demonstrated to occur in blood. The latter also represents a mechanism for the transport of homocysteine in plasma. In addition, homocysteine thiolactone has been shown to react with free amino groups in proteins to form isopeptide bonds, in particular at the lysine residue level. Another type of isopeptide bond in proteins may result from the deamidation and isomerization of asparaginyl residues, yielding abnormal isoaspartyl residues, which have been demonstrated to be increased in uremic patients. Folate treatment exerts a partial, but significant, homocysteine-lowering effect in uremic patients and has been shown to improve the changes in macromolecules induced by high homocysteine levels. In conclusion, both DNA and proteins are structurally modified in uremia as a consequence of high homocysteine levels. The role of these macromolecule changes in inducing the clinical complications of hyperhomocysteinemia in these patients, although still conjectural in some respects, is at present sustained by several pieces of evidence.

Keywords: DNA methylation; hyperhomocysteinemia; isopeptide bonds; uremia
Corresponding author: Alessandra F. Perna, MD, PhD, First Division of Nephrology, School of Medicine and Surgery, S.U.N., via Sergio Pansini 5, 80138 Naples, Italy Phone: +39-081-5666668, Fax: +39-081-5665836,

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Published Online: 2011-9-21
Published in Print: 2005-10-1

©2005 by Walter de Gruyter Berlin New York

Artikel in diesem Heft

  1. Homocysteine research – where do we stand and where are we going?
  2. Hyperhomocysteinemia and arteriosclerosis: historical perspectives
  3. Homocysteine and heart failure: a review of investigations from the Framingham Heart Study
  4. Homocysteine and vascular disease in diabetes: a double hit?
  5. Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia
  6. Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?
  7. Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
  8. Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients
  9. Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy
  10. Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
  11. Hyperhomocysteinemia and macromolecule modifications in uremic patients
  12. Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients
  13. Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
  14. Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects
  15. Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
  16. A laboratory algorithm with homocysteine as the primary parameter reduces the cost of investigation of folate and cobalamin deficiency
  17. Betaine: a key modulator of one-carbon metabolism and homocysteine status
  18. Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
  19. Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
  20. Homocysteine in relation to cognitive performance in pathological and non-pathological conditions
  21. Homocysteine and B vitamins in mild cognitive impairment and dementia
  22. Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
  23. Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions
  24. Homocysteine – a newly recognised risk factor for osteoporosis
  25. Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women
  26. Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality
  27. Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
  28. Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
  29. Asymmetric dimethylarginine, homocysteine and renal function – is there a relation?
  30. Interactions between folate and aging for carcinogenesis
  31. The potential cocarcinogenic effect of vitamin B12 deficiency
  32. The vegetarian lifestyle and DNA methylation
https://doi.org/10.1515/CCLM.2005.181
Schlagwörter für diesen Artikel
DNA methylation; hyperhomocysteinemia; isopeptide bonds; uremia

Artikel in diesem Heft

  1. Homocysteine research – where do we stand and where are we going?
  2. Hyperhomocysteinemia and arteriosclerosis: historical perspectives
  3. Homocysteine and heart failure: a review of investigations from the Framingham Heart Study
  4. Homocysteine and vascular disease in diabetes: a double hit?
  5. Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia
  6. Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?
  7. Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
  8. Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients
  9. Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy
  10. Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
  11. Hyperhomocysteinemia and macromolecule modifications in uremic patients
  12. Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients
  13. Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
  14. Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects
  15. Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
  16. A laboratory algorithm with homocysteine as the primary parameter reduces the cost of investigation of folate and cobalamin deficiency
  17. Betaine: a key modulator of one-carbon metabolism and homocysteine status
  18. Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
  19. Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
  20. Homocysteine in relation to cognitive performance in pathological and non-pathological conditions
  21. Homocysteine and B vitamins in mild cognitive impairment and dementia
  22. Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
  23. Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions
  24. Homocysteine – a newly recognised risk factor for osteoporosis
  25. Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women
  26. Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality
  27. Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
  28. Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
  29. Asymmetric dimethylarginine, homocysteine and renal function – is there a relation?
  30. Interactions between folate and aging for carcinogenesis
  31. The potential cocarcinogenic effect of vitamin B12 deficiency
  32. The vegetarian lifestyle and DNA methylation
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