title: Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia.
abstract: Thermolability of 5,10-methylenetetrahydrofolate reductase (MTHFR) was examined as a possible cause of mild hyperhomocysteinemia in patients with premature vascular disease. Control subjects and vascular patients with mild hyperhomocysteinemia and with normohomocysteinemia were studied. The mean (+/- SD) specific MTHFR activity in lymphocytes of 22 control subjects was 15.6 (+/- 4.7) nmol CH2O/mg protein/h (range: 9.1-26.6), and the residual activity (+/- SD) after heat inactivation for 5 min at 46 degrees C was 55.3 (+/- 12.0)% (range: 35.9-78.3). By measurement of MTHFR activity, two distinct subgroups of hyperhomocysteinemic patients became evident. One group (n = 11) had thermolabile MTHFR with a mean (+/- SD) specific activity of 8.7 (+/- 2.1) nmol CH2O/mg protein/h (range: 5.5-12.7) and a residual activity, after heat inactivation, ranging from 0% to 33%. The other group (n = 28) had normal specific activity (+/- SD) of 21.5 (+/- 7.2) nmol CH2O/mg protein/h (range: 10.0-39.0) and a normal residual activity (+/- SD) of 53.8 (+/- 9.2)% (range: 33.1-71.5) after heat inactivation. The mean (+/- SD) specific activity of 29 normohomocysteinemic patients was 20.7 (+/- 6.5) nmol CH2O/mg protein/h (range: 9.4-33.8), and the mean (+/- SD) residual activity after heat inactivation was 58.2 (+/- 10.2)% (range: 43.0-82.0). Thus, in 28% of the hyperhomocysteinemic patients with premature vascular disease, abnormal homocysteine metabolism could be attributed to thermolabile MTHFR.
authors: Department of Pediatrics, University Hospital Nijmegen, The Netherlands.
authors: A M
authors: AM
authors: Engbersen
authors: D G
authors: DG
authors: Franken
authors: G H
authors: GH
authors: Boers
authors: E M
authors: EM
authors: Stevens
authors: F J
authors: FJ
authors: Trijbels
authors: H J
authors: HJ
authors: Blom
mesh_terms: D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D002478:Cells, Cultured; D003541:Cystathionine beta-Synthase / Q000032:analysis; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006710:Homocysteine / Q000097:blood*; D006358:Hot Temperature; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D010088:Oxidoreductases / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics; D011489:Protein Denaturation; D012307:Risk Factors; D014652:Vascular Diseases / Q000201:enzymology / Q000453:epidemiology / Q000209:etiology*
chemical_list: D006710:Homocysteine; D010088:Oxidoreductases; D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003541:Cystathionine beta-Synthase