title: Low whole-blood S-adenosylmethionine and correlation between 5-methyltetrahydrofolate and homocysteine in coronary artery disease.
abstract: Mild elevation of plasma homocysteine is an independent risk factor for vascular disease. We studied the role of 5-methyltetrahydrofolate (5-MTHF), the folate form directly involved in homocysteine metabolism, in contrast to previous studies, which used total folate measurements, in 70 coronary artery disease (CAD) patients and control subjects. We also measured S-adenosylmethionine (SAM), which controls the activity of critical enzymes of homocysteine metabolism. Fasting plasma total homocysteine was elevated (> 12.4 mumol/L for women, > 13.3 mumol/L for men) in 17% of patients, in accordance with earlier studies. These patients showed lower 5-MTHF (12.4 +/- 1.0 mumol/L, mean +/- SD) than control subjects (24.2 +/- 15.0, P < .001), and there was a clear correlation (multiple linear regression analysis: P = .002) of this relevant form of folate with homocysteine. However, 37% of the normohomocysteinemic patients also revealed similarly low 5-MTHF levels, suggesting that a decrease of 5-MTHF does not necessarily cause hyperhomocysteinemia. SAM was significantly decreased in patients (1.4 +/- 0.4 mumol/L) compared with control subjects (1.8 +/- 0.3, P < .001) but was not correlated to homocysteine or 5-MTHF. The correlation between homocysteine and 5-MTHF that was found in CAD patients but not in control subjects confirms the direct relationship between these compounds in vivo. The new finding of low SAM in patients demands further studies, since it might indicate that low levels pose risk and that SAM might be a protective factor against the development of CAD.
authors.affiliation: Metabolic Unit, University Children's Hospital, Basel, Switzerland.
authors.forename: F M
authors.initials: FM
authors.lastname: Loehrer
authors.forename: C P
authors.initials: CP
authors.lastname: Angst
authors.forename: W E
authors.initials: WE
authors.lastname: Haefeli
authors.forename: P P
authors.initials: PP
authors.lastname: Jordan
authors.forename: R
authors.initials: R
authors.lastname: Ritz
authors.forename: B
authors.initials: B
authors.lastname: Fowler
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D008716:Methionine Adenosyltransferase / Q000378:metabolism; D008745:Methylation; D008875:Middle Aged; D012307:Risk Factors; D012436:S-Adenosylmethionine / Q000097:blood / Q000172:deficiency*; D013763:Tetrahydrofolates / Q000097:blood*
chemical_list: D007527:Isoenzymes; D013763:Tetrahydrofolates; D006710:Homocysteine; D012436:S-Adenosylmethionine; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D008716:Methionine Adenosyltransferase; C005984:5-methyltetrahydrofolate