Evidence for disturbed S-adenosylmethionine:S-adenosylhomocysteine ratio in patients with end-stage renal failure:: A cause for disturbed methylation reactions?

被引:99
作者
Loehrer, FMT
Angst, CP
Brunner, FP
Haefeli, WE
Fowler, B [1 ]
机构
[1] Univ Basel, Childrens Hosp, Metab Unit, CH-4005 Basel, Switzerland
[2] Univ Basel Hosp, Dept Med, Div Clin Pharmacol, Basel, Switzerland
[3] Univ Basel Hosp, Dept Med, Div Nephrol, Basel, Switzerland
[4] Univ Basel, Dept Pharm, CH-4005 Basel, Switzerland
关键词
S-adenosylhomocysteine; S-adenosylmethionine; cardiovascular disease; end-stage renal disease; homocysteine; methylation;
D O I
10.1093/ndt/13.3.656
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Background. Elevated homocysteine concentrations have been associated with premature arteriosclerosis and with impairment of key methylation reactions through accumulation of the homocysteine metabolite S-adenosylhomocysteine. In end-stage renal failure high homocysteine concentrations are commonly found but thus far the concentrations of related adenosylated metabolites in plasma have not been assessed. Methods. In this prospective study we determined plasma homocysteine and related metabolites in 25 patients on regular haemodialysis, and in 40 healthy volunteers. Blood samples from patients were drawn immediately before and in 10 patients additionally after the dialysis session. Results. Folic acid and vitamin B-12 in plasma were similar in patients (mean+/-SEM 25+/-2 nmol/l and 400+/-41 pmol/l respectively) and controls (24+/-3 and 324+/-23 respectively). In patients plasma homocysteine, S-adenosylmethionine and S-adenosylhomocysteine were markedly elevated (36.6+/-3.6 mu mol/l, 381+/-32 nmol/l and 1074+/-55 nmol/l respectively) compared to the control values (6.8+/-0.4 mu mol/l, 60+/-3 nmol/l and 24.4+/-1.1 nmol/l respectively) whereas the molar ratio of plasma S-adenosylmethionine and S-adenosylhomocysteine was significantly decreased (0.36+/-0.02 and 2.7+/-0.2 in patients and controls respectively). Haemodialysis failed to normalize the abnormal levels of these metabolites. Conclusion. Since the ratio of S-adenosylmethionine : S-adenosylhomocysteine is closely linked to the activity of numerous enzymatic methylation reactions, these results suggest that methylation may be impaired in these patients.
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页码:656 / 661
页数:6
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