Document Detail


Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology.
MedLine Citation:
PMID:  8364009     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mild homocysteinemia occurs surprisingly often in patients with premature vascular disease. We studied the possible enzymatic sources of this mild hyperhomocysteinemia and the control of homocysteine levels in plasma by treatment of patients with the cofactors and cosubstrates of homocysteine catabolism. We assessed homocysteine metabolism in 131 patients who had premature disease in their coronary, peripheral, or cerebrovascular circulation by using a standard oral methionine-load test. Impaired homocysteine metabolism occurred in 28 patients. We assayed levels of the primary enzymes of homocysteine catabolism in cultured skin fibroblast extracts from 15 of these 28 patients. The patients' cystathionine beta-synthase levels (3.68 +/- 2.52 nmol/h per milligram of cell protein, mean +/- SD) were markedly depressed compared with those from 31 healthy adult control subjects (7.61 +/- 4.49, P < .001). The patients' levels of 5-methyltetrahydrofolate: homocysteine methyltransferase were normal. While betaine: homocysteine methyltransferase was not expressed in skin fibroblasts, 24-hour urinary betaine and N,N-dimethylglycine measurements were consistent with normal or enhanced remethylation of homocysteine by betaine: homocysteine methyltransferase in the 13 patients tested. When treated daily with choline and betaine, pyridoxine, or folic acid, there was a normalization of the postmethionine plasma homocysteine level in 16 of 19 patients. Our results indicate that mild homocysteinemia in premature vascular disease may be caused by either a folate deficiency or deficiencies in cystathionine beta-synthase activity. It does not necessarily involve deficiencies of either 5-methyltetrahydrofolate:homocysteine methyltransferase or betaine:homocysteine methyltransferase. Effective treatment regimens are also defined.
Authors:
N P Dudman; D E Wilcken; J Wang; J F Lynch; D Macey; P Lundberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association     Volume:  13     ISSN:  1049-8834     ISO Abbreviation:  Arterioscler. Thromb.     Publication Date:  1993 Sep 
Date Detail:
Created Date:  1993-10-01     Completed Date:  1993-10-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9101388     Medline TA:  Arterioscler Thromb     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1253-60     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of New South Wales, Prince Henry Hospital, Little Bay, NSW, Australia.
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MeSH Terms
Descriptor/Qualifier:
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / metabolism
Adolescent
Adult
Aged
Betaine-Homocysteine S-Methyltransferase
Cerebrovascular Disorders / metabolism*
Coronary Disease / drug therapy,  metabolism*
Cystathionine beta-Synthase / metabolism
Female
Homocysteine / metabolism*
Humans
Male
Methionine / metabolism*
Methyltransferases / metabolism
Middle Aged
Peripheral Vascular Diseases / metabolism*
Vitamins / therapeutic use
Chemical
Reg. No./Substance:
0/Vitamins; 454-28-4/Homocysteine; 63-68-3/Methionine; EC 2.1.1.-/Methyltransferases; EC 2.1.1.13/5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; EC 2.1.1.5/BHMT protein, human; EC 2.1.1.5/Betaine-Homocysteine S-Methyltransferase; EC 4.2.1.22/Cystathionine beta-Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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