Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology

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Dudman, N. P. B.Department of Medicine, University of New South Wales, Prince Henry Hospital, Uttle Bay, UK (författare)

Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology

Artikel/kapitelEngelska1993

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American Heart Association,1993
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Nummerbeteckningar

LIBRIS-ID:oai:DiVA.org:liu-114161
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-114161URI
https://doi.org/10.1161/01.ATV.13.9.1253DOI

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Språk:engelska
Sammanfattning på:engelska

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Ämneskategori:art swepub-publicationtype

Anmärkningar

1049-8834 (Print) Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.
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.

Ämnesord och genrebeteckningar

NATURVETENSKAP Kemi Fysikalisk kemi hsv//swe
NATURAL SCIENCES Chemical Sciences Physical Chemistry hsv//eng
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

Biuppslag (personer, institutioner, konferenser, titlar ...)

Wilcken, D. E.Department of Medicine, University of New South Wales, Prince Henry Hospital, Uttle Bay, UK (författare)
Wang, J.Department of Medicine, University of New South Wales, Prince Henry Hospital, Uttle Bay, UK (författare)
Lynch, J. F.Department of Medicine, University of New South Wales, Prince Henry Hospital, Uttle Bay, UK (författare)
Macey, D.Department of Medicine, University of New South Wales, Prince Henry Hospital, Uttle Bay, UK (författare)
Lundberg, PeterLinköpings universitet,Avdelningen för radiologiska vetenskaper,Hälsouniversitetet,Centrum för medicinsk bildvetenskap och visualisering, CMIV,Region Östergötland, Radiofysikavdelningen US,Department of Biochemistry, University of Sydney, Sydney (P.L.), Australia(Swepub:liu)petlu11 (författare)
Department of Medicine, University of New South Wales, Prince Henry Hospital, Uttle Bay, UKAvdelningen för radiologiska vetenskaper (creator_code:org_t)

Sammanhörande titlar

Ingår i:Arteriosclerosis, Thrombosis and Vascular Biology: American Heart Association13:9, s. 1253-12601079-56421524-4636

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Arteriosclerosis, Thrombosis and Vascular Biology (Sök värdpublikationen i LIBRIS)

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Av författaren/redakt...: Dudman, N. P. B.; Wilcken, D. E.; Wang, J.; Lynch, J. F.; Macey, D.; Lundberg, Peter

Om ämnet

NATURVETENSKAP: NATURVETENSKAP; och Kemi; och Fysikalisk kemi

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Av lärosätet: Linköpings universitet

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