Homocysteine and methionine metabolism in ESRD: A stable isotope study

Abstract

The conversion of homocysteine to methionine is substantially (approximately 30%) decreased in hemodialysis patients, whereas transsulfuration is not. Decreased remethylation may explain hyperhomocysteinemia in ESRD. This stable isotope technique is applicable for developing new and effective homocysteine-lowering treatment regimens in ESRD based on pathophysiological mechanisms.

Disturbed Homocysteine and Methionine Cycle Intermediates S-Adenosylhomocysteine and S-Adenosylmethionine Are Related to Degree of Renal Insufficiency in Type 2 Diabetes

“…On the other hand, a lower rate of plasma Hcy clearance was observed in HHcy in renal patients compared with healthy persons, which suggests a role for the kidney in the elimination of this aminothiol (33 ). The remethylation of Hcy to methionine is lower in hemodialysis patients (34 ). In addition, Hcy remethylation was shown to be impaired in dialysis patients despite serum concentrations of vitamin B 12 and folate being well above those found in the general population (4 ).…”

Hyperhomocysteinemia Associated With Decreased Renal Transsulfuration Activity in Dahl S Rats

“…Most (85% to 100%) patients with end-stage renal disease have hHcys. 15 It has been indicated that the hHcys in end-stage renal disease is induced by the abnormality of Hcys metabolism in the kidneys but not simply because of reduced glomerular filtration of Hcys. 10,15,16 Although these observations suggest a major role for the kidneys in Hcys elimination, the role of the kidneys in the development of hHcys and the possible mechanisms leading to impaired clearance of Hcys by the kidneys have yet to be elucidated.…”

Remethylation and transsulfuration of methionine in cirrhosis: Studies with L -[2 H3 -methyl-1-13 C]methionine

“…13 CO 2 arises either from transsulfuration of HCY to cysteine, decarboxylation of AdoMET or transamination, and subsequent decarboxylation of MET. Decarboxylation of AdoMET is a minor pathway in healthy subjects.…”

“…Metabolism of MET and its investigation with stable isotopes. If L-[ 2 H 3 -methyl-1- 13 C]methionine (m/z ϭ ϩ 4) enters the MET cycle, the methyl label will get lost during transmethylation from AdoMET to AdoHCY. Remethylated MET then can be detected in plasma with a mass of m/z ϭ ϩ 1.…”

“…This approach using either continuously infused or orally administered tracer has been previously used to investigate MET metabolism in healthy subjects [9][10][11][12] and patients with end-stage renal disease. 13 …”