PMID- 16197295
OWN - NLM
STAT- MEDLINE
DCOM- 20051202
LR  - 20161018
IS  - 1434-6621 (Print)
IS  - 1434-6621 (Linking)
VI  - 43
IP  - 10
DP  - 2005
TI  - Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin 
      treatment in renal patients.
PG  - 1039-47
AB  - The role of hyperhomocysteinemia (HHcy) as a risk marker for cardiovascular 
      diseases in renal patients is a matter of controversy. The remethylation of 
      homocysteine (Hcy) to methionine in the kidneys is of great importance for Hcy 
      clearance. Hcy remethylation is markedly decreased in patients on hemodialysis, 
      but transsulfuration remains mostly unaffected. Markedly increased concentrations 
      of methylmalonic acid (MMA), as a metabolic marker of vitamin B12 deficiency, 
      have been found in approximately 70% of renal patients. This is in contrast to 
      normal concentrations of vitamin B12 usually reported in such patients. We 
      demonstrated in cell culture experiments that the uptake of vitamin B12 by 
      mononuclear cells from renal patients was lower than that taken up by cells from 
      controls. The lowering of MMA and Hcy concentrations in renal patients after B12 
      administration may indicate the presence of intracellular pre-treatment 
      deficiency. We administered folic acid (5 mg) plus vitamin B6 (50 mg) and B12 
      (0.7 mg) three times per week intravenously to hyperhomocysteinemic dialysis 
      patients. Hcy decreased after 4 weeks by 51%. Hcy was normalized in almost all 
      patients, while serum concentrations of MMA and cystathionine were reduced by 28% 
      and 26%, respectively. Cystathionine, an indicator for the transsulfuration 
      pathway, showed a drastic increase in renal disease and was only slightly lowered 
      by B-vitamin treatment. The increased cystathionine/cysteine ratio in renal 
      patients indicates possible impairment of the catabolism of cystathionine by 
      cystathionase. Moreover, renal failure is associated with severe abnormalities in 
      plasma concentrations of S-adenosyl Hcy (SAH) and S-adenosyl methionine (SAM), as 
      well as the SAM/SAH ratio. This ratio is an indicator of the availability of 
      methyl groups from SAM. Therapeutic doses of B-vitamins in dialysis patients led 
      to a limited improvement in the biomarkers of methylation and probably did not 
      have a significant effect on transmethylation potential in the cells. 
      Furthermore, elevated serum levels of asymmetric dimethylarginine (ADMA) in renal 
      patients, which are associated with a poor outcome for such patients, could be 
      lowered, but this effect was confined to patients who had no anemia. Future 
      studies may consider extending the duration of vitamin treatment, as well as 
      agents that may enhance the hydrolysis of SAH and cystathionine.
FAU - Herrmann, Wolfgang
AU  - Herrmann W
AD  - Department of Clinical Chemistry and Laboratory Medicine, School of Medicine, 
      Saarland University, Germany. kchwher@uniklinilum-saarland.de
FAU - Obeid, Rima
AU  - Obeid R
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Germany
TA  - Clin Chem Lab Med
JT  - Clinical chemistry and laboratory medicine
JID - 9806306
RN  - 0 (Vitamins)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Animals
MH  - Homocysteine/metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/*drug therapy/*metabolism
MH  - Kidney Diseases/*drug therapy/*metabolism
MH  - Methionine/*metabolism
MH  - Methylation
MH  - Vitamins/pharmacology/*therapeutic use
RF  - 74
EDAT- 2005/10/04 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/10/04 09:00
PHST- 2005/10/04 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/10/04 09:00 [entrez]
AID - 10.1515/CCLM.2005.182 [doi]
PST - ppublish
SO  - Clin Chem Lab Med. 2005;43(10):1039-47. doi: 10.1515/CCLM.2005.182.