Abstract
BackgroundMethionine loading test (MLT) has been used primarily to identify defects in transsulfuration of homocysteine in cystathionine beta synthase deficiency. It may not be as useful to evaluate remethylation pathway, in vitamin B-12 and folate deficiencies.ObjectiveWe used tracer isotope labelled MLT to interrogate transsulfuration and remethylation independently in vitamin B-12 deficiency.DesignWe studied vitamin B-12 deficient women with a tracer labelled MLT before and eleven months after treatment with vitamin B-12. The fractional contribution of [13C]homocysteine to breath CO2 was used as a measure of transsulfuration, and difference in the intracellular enrichment of [13C]methionine and that of [C2H3]methionine as a measure of remethylation of homocysteine. Combined pre- and post-treatment results were analyzed to investigate the association between plasma vitamin B-12 concentrations and measures of homocysteine metabolism.ResultsThe subjects were 17 years old, with a BMI of 19.4 kg/m2. Treatment with vitamin B-12, 2µg/day increased plasma B-12 from 93 (78.7, 106.2) [median (25th, 75th centiles)] to 161.5 (125.5, 226.2) pmol/L; 44% were below <150pmol/L after treatment. Fasting homocysteine concentration was significantly lower and that of cysteine higher in subjects with B-12 levels >150pmol/L. The tracer estimated transsulfuration of homocysteine was lower and remethylation higher with B-12 levels >150pmol/L when compared with those <150pmol/L.ConclusionsThe tracer labelled MLT in combination with fasting parameters is a robust way to estimate parameters of methionine metabolism and can be used in the field where prime-constant rate infusion studies cannot be done efficiently.
Highlights
Methionine loading test was originally introduced to identify subjects with defects in transsulfuration due to congenital cystathionine beta synthase defects or due to pyridoxine phosphate deficiency
Vitamin B-12 is a cofactor for methionine synthase, which catalyzes the methylation of homocysteine to form methionine
We examined the perturbations in markers of one carbon metabolism in multi-nutrient insufficient Indian women and nutritionally sufficient American women [11]
Summary
Methionine loading test was originally introduced to identify subjects with defects in transsulfuration due to congenital cystathionine beta synthase defects or due to pyridoxine phosphate deficiency. We postulated that a tracer labelled methionine load, by measuring the remethylation (Rm) and transsulfuration (Ts) directly and independently, will be a robust and informative test for the interrogation of the methionine metabolism in B-12 deficient subjects and other clinical states. Oral methionine load showed a greater increase in homocysteine concentration in the Indian subjects compared with the Americans which could be the result of the combined effect of decrease in transsulfuration (primarily) and of remethylation of homocysteine. Methionine loading test (MLT) has been used primarily to identify defects in transsulfuration of homocysteine in cystathionine beta synthase deficiency. It may not be as useful to evaluate remethylation pathway, in vitamin B-12 and folate deficiencies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
