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Original Article
Brief Report
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Volume 349:45-50 July 3, 2003 Number 1
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Adverse Effect of Nitrous Oxide in a Child with 5,10-Methylenetetrahydrofolate Reductase Deficiency
Rebecca R. Selzer, Ph.D., David S. Rosenblatt, M.D., Renata Laxova, M.D., and Kirk Hogan, M.D., J.D.

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 by Erbe, R. W.
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Nitrous oxide irreversibly oxidizes the cobalt atom of vitamin B12, thereby inhibiting the activity of the cobalamin-dependent enzyme methionine synthase (or 5-methyltetrahydrofolate–homocysteine S-methyltransferase; Enzyme Commission code EC 2.1.1.13). Methionine synthase catalyzes the remethylation of 5-methyltetrahydrofolate and homocysteine to tetrahydrofolate and methionine (Figure 1). Methionine, by way of its activated form, S-adenosylmethionine, is the principal substrate for methylation in many biochemical reactions, including assembly of the myelin sheath, methyl substitutions in neurotransmitters, and DNA synthesis in rapidly proliferating tissues.1

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Figure 1. The Folate and Homocysteine Metabolic Cycles and the Enzymatic Site of Nitrous Oxide Toxicity.

Co denotes cobalt.

 
We report . . . [Full Text of this Article]

Case Report

Methods

Fibroblast Culture and MTHFR Activity

Preparation and Sequence Analysis of Genomic DNA

RNA Analysis

Results

Enzyme Activity in Fibroblasts

Genomic DNA-Sequence Analysis

RNA Analysis

Discussion


Source Information

From the Departments of Anesthesiology (R.R.S., K.H.) and Medical Genetics (R.L.), University of Wisconsin Medical School, Madison; and the Departments of Human Genetics, Medicine, Pediatrics, and Biology, McGill University, Montreal (D.S.R.).

Address reprint requests to Dr. Hogan at the Department of Anesthesiology, B6/319 Clinical Sciences Center, 600 Highland Ave., Madison, WI 53792, or at khogan@facstaff.wisc.edu.


Related Letters:

Nitrous Oxide and 5,10-Methylenetetrahydrofolate Reductase
Burman J. F., Kaufman J. L., Hogan K., Erbe R. W.
Extract | Full Text | PDF  
N Engl J Med 2003; 349:1479-1480, Oct 9, 2003. Correspondence

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