Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia

• Published in: American journal of human genetics 1995, Vol.56 (1), p.142-150
• Main Authors: ENGBERSEN, A. M. T, FRANKEN, D. G, BOERS, G. H. J, STEVENS, E. M. B, TRIJBELS, F. J. M, BLOM, H. J
• Format: Article
• Language: English
• Subjects: 5,10-Methylenetetrahydrofolate Reductase (FADH2); Adult; Amino Acid Metabolism, Inborn Errors - blood; Amino Acid Metabolism, Inborn Errors - complications; Amino Acid Metabolism, Inborn Errors - enzymology; Amino Acid Metabolism, Inborn Errors - genetics; Aminoacid disorders; Biological and medical sciences; Cells, Cultured; Cystathionine beta-Synthase - analysis; Errors of metabolism; Female; Fibroblasts - enzymology; Homocysteine - blood; Hot Temperature; Humans; Lymphocytes - enzymology; Male; Medical sciences; Metabolic diseases; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases - chemistry; Oxidoreductases - deficiency; Oxidoreductases - genetics; Protein Denaturation; Risk Factors; Vascular Diseases - enzymology; Vascular Diseases - epidemiology; Vascular Diseases - etiology
• ISSN: 0002-9297; 1537-6605

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.