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Defects in homocysteine metabolism: diversity among hyperhomocyst(e)inemias
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Rowena G. Matthews
Published/Copyright:
December 8, 2007
Abstract
There are now four genetic mouse models that induce hyperhomocyst(e)inemia by decreasing the activity of an enzyme involved in homocysteine metabolism: cystathionine β-synthase, methylenetetrahydrofolate reductase, methionine synthase and methionine synthase reductase. While each enzyme deficiency leads to murine hyperhomocyst(e)inemia, the accompanying metabolic profiles are significantly and often unexpectedly, different. Deficiencies in cystathionine β-synthase lead to elevated plasma methionine, while deficiencies of the remaining three enzymes lead to hypomethioninemia. The liver [S-adenosylmethionine]/[S-adenosylhomocysteine] ratio is decreased in mice lacking methylenetetrahydrofolate reductase or cystathionine β-synthase, but unexpectedly increased in mice with deficiencies in methionine synthase or methionine synthase reductase. Folate pool imbalances are observed in complete methylenetetrahydrofolate reductase deficiency, where methyltetra-hydrofolate is a minor component, and in methionine synthase reductase deficiency, where methyltetrahydrofolate is increased relative to wild-type mice. These differences illustrate the potential diversity among human patients with hyperhomocyst(e)inemia, and strengthen the argument that the pathologies associated with the dissimilar forms of the condition will require different treatments.
Clin Chem Lab Med 2007;45:1700–3.
Keywords: adenosylhomocysteine; adenosylmethionine; cystathionine β-synthase; folate; genetic mouse models; homocysteine; methionine synthase; methionine synthase reductase; methylenetetrahydrofolate reductase
Received: 2007-6-20
Accepted: 2007-7-30
Published Online: 2007-12-08
Published in Print: 2007-12-01
©2007 by Walter de Gruyter Berlin New York
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- Contents, Volume 45, 2007
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Articles in the same Issue
- Homocysteine research: alive and kicking!
- Homocysteine-lowering trials for prevention of vascular disease: protocol for a collaborative meta-analysis
- Perspective on the efficacy analysis of the Vitamin Intervention for Stroke Prevention trial
- Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients
- The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases
- Management of L-Dopa related hyperhomocysteinemia: catechol-O-methyltransferase (COMT) inhibitors or B vitamins? Results from a review
- Biomarkers of folate and vitamin B12 status in cerebrospinal fluid
- The role of hyperhomocysteinemia as well as folate, vitamin B6 and B12 deficiencies in osteoporosis – a systematic review
- Homocysteine, brain natriuretic peptide and chronic heart failure: a critical review
- Homocysteine, left ventricular dysfunction and coronary artery disease: is there a link?
- Hyperhomocysteinemia and high-density lipoprotein metabolism in cardiovascular disease
- Hyperhomocysteinemia, DNA methylation and vascular disease
- Measuring subclinical atherosclerosis: is homocysteine relevant?
- Plasma protein homocysteinylation in uremia
- Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease
- Hyperhomocysteinemia – association with renal transsulfuration and redox signaling in rats
- Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine
- Defects in homocysteine metabolism: diversity among hyperhomocyst(e)inemias
- The molecular basis of homocysteine thiolactone-mediated vascular disease
- Importance of folate-homocysteine homeostasis during early embryonic development
- Association between homocysteine, vitamin B6 concentrations and inflammation
- Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry
- Holotranscobalamin in laboratory diagnosis of cobalamin deficiency compared to total cobalamin and methylmalonic acid
- Haptocorrin in humans
- Small ubiquitin-like modifier-1 (SUMO-1) modification of thymidylate synthase and dihydrofolate reductase
- Decreased p66Shc promoter methylation in patients with end-stage renal disease
- Synergism between AT1 receptor and hyperhomocysteinemia during vascular remodeling
- Differential expression of γ-aminobutyric acid receptor A (GABAA) and effects of homocysteine
- The effect of B-vitamins on biochemical bone turnover markers and bone mineral density in osteoporotic patients: a 1-year double blind placebo controlled trial
- Acknowledgement
- Contents, Volume 45, 2007
- Author Index
- Subject Index
