Format

Send to:

Choose Destination
See comment in PubMed Commons below
Clin Chem Lab Med. 2007;45(12):1700-3.

Defects in homocysteine metabolism: diversity among hyperhomocyst(e)inemias.

Author information

  • 1Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA. rmatthew@umich.edu

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 beta-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 beta-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 beta-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.

PMID:
17937607
[PubMed - indexed for MEDLINE]
PMCID:
PMC3098622
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for iFactory Icon for PubMed Central
    Loading ...
    Write to the Help Desk