Homocysteine clearance and methylation flux rates in health and end-stage renal disease: association with S-adenosylhomocysteine

Hyperhomocysteinemia is a risk factor for cardiovascular disease and occurs frequently in end-stage renal disease (ESRD), but its pathogenesis is poorly understood. We aimed to evaluate one-carbon flux rates of methionine and homocysteine (Hcy) in ESRD patients and healthy controls. Transmethylation...

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Published in:American journal of physiology. Renal physiology 2004-08, Vol.56 (2), p.F215-F223
Main Authors: STAM, Frank, VAN GULDENER, Coen, TER WEE, Piet M, KULIK, Willem, SMITH, Desirée E. C, JAKOBS, Cornelis, STEHOUWER, Coen D. A, DE MEER, Kees
Format: Article
Language:English
Subjects:
Biological and medical sciences
Blood
Circulatory system
Fundamental and applied biological sciences. Psychology
Kidney diseases
Molecules
Vertebrates: urinary system
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Summary:Hyperhomocysteinemia is a risk factor for cardiovascular disease and occurs frequently in end-stage renal disease (ESRD), but its pathogenesis is poorly understood. We aimed to evaluate one-carbon flux rates of methionine and homocysteine (Hcy) in ESRD patients and healthy controls. Transmethylation (TM), remethylation (RM), and transsulfuration (TS), as well as Hcy clearance by TS (i.e., TS/plasma total Hcy concentration) and by RM (i.e., RM/plasma total Hcy concentration) were evaluated in relation to body composition, vitamins, and S-adenosylhomocysteine (AdoHcy) and S-adenosylmethionine (AdoMet) levels. After a fixed protein diet for 3 days, primed-continuous infusion of [2H3-methyl-1-13C]methionine was performed in the postabsorptive state in 12 hemodialysis patients and 16 healthy volunteers. Hcy clearance by TS (-80%, P < 0.001) and by RM (-77%, P < 0.001) in ESRD patients was decreased compared with healthy controls. The absolute flux rates of TM (-27%, P < 0.01) and RM (-28%, P = 0.02) were lower in the ESRD patients. After adjustment for age, TS was not significantly reduced. Whole blood AdoHcy was significantly elevated in ESRD and was a significant determinant of TM (standardized = -1.24, P = 0.01) and RM (standardized = -1.43, P = 0.03). In conclusion, patients with ESRD have impaired Hcy clearance by TS and RM. Elevated whole blood AdoHcy levels are associated with impaired RM and TM flux rates in these patients, and AdoHcy may be a key regulatory compound in one-carbon flux. [PUBLICATION ABSTRACT]
ISSN:1931-857X
1522-1466