期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 286, 期 2, 页码 E272-E279出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00351.2003
关键词
methionine; methylation cycle; cystathionine
资金
- NCRR NIH HHS [M01 RR-00082] Funding Source: Medline
- NIDDK NIH HHS [DK-56274, DK-42033] Funding Source: Medline
Hyperhomocysteinemia in humans is associated with genetic variants of several enzymes of folate and one-carbon metabolism and deficiencies of folate and vitamins B-12 and B-6. In each case, hyperhomocysteinemia might be caused by diminished folate-dependent homocysteine remethylation, but this has not been confirmed in vivo. Because published stable isotopic tracer approaches cannot distinguish folate-dependent from folate-independent remethylation, we developed a dual-tracer procedure in which a [U-C-13(5)]methionine tracer is used in conjunction with a [3-C-13] serine tracer to simultaneously measure rates of total and folate-dependent homocysteine remethylation. In young female subjects, plasma [U-C-13(4)] homocysteine enrichment, a surrogate measure of intracellular [ U-C-13(5)] methionine enrichment, reached similar to90% of the plasma [U-C-13(5)] methionine enrichment. Methionine-methyl and -carboxyl group fluxes were in the range of previous reports (similar to25 and similar to17 mumol.kg(-1).h(-1), respectively). However, the rate of overall homocysteine remethylation (similar to8 mumol.kg(-1).h(-1)) was twice that of previous reports, which suggests a larger role for homocysteine remethylation in methionine metabolism than previously thought. By use of estimates of intracellular [3-C-13] serine enrichment based on a conservative correction of plasma [3-C-13] serine enrichment, serine was calculated to contribute similar to100% of the methyl groups used for total body homocysteine remethylation under the conditions of this protocol. This contribution represented only a small fraction (similar to2.8%) of total serine flux. Our dual-tracer procedure is well suited to measure the effects of nutrient deficiencies, genetic polymorphisms, and other metabolic perturbations on homocysteine synthesis and total and folate-dependent homocysteine remethylation.
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