Changes in the concentration of sulfur-containing amino acids in the brain after methionine load in the experimentChanges in the concentration of sulfur-containing amino acids in the brain after methionine load in the experiment

The effect of methionine overload on the state of the pool of sulfur-containing amino acids and their metabolites was studied in the various brain structures determined by reverse phase high performance liquid chromatography (HPLC). In all regions of the brain studied, methionine led to a unidirectional imbalance of sulfur-containing compounds: there was an increase in the concentrations of methionine, cystathionine and hypotaurine. The most pronounced increase in methionine and hypotaurine levels was observed in the striatum, cystathionine in the hemispheres. A significant increase in taurine concentration was observed only in the hypothalamus and striatum. In other parts of the brain a tendency to increase its level was shown. In all brain regions studied except the striatum, serine levels were decreased. In the cerebellum, in comparison with other regions, an increase in the level of cysteic acid and a decrease in the level of cysteinesulfinic acid were observed, which indicates that taurine synthesis is occurred mainly through the cysteine sulfinate oxidation.

Cystathionine β-synthase and methylenetetrahydrofolate reductase mutations in Mexican individuals with hyperhomocysteinemia

Background: Hyperhomocysteinemia, a thrombotic risk factor, may have several causes. Among the genetic causes of hyperhomocysteinemia, there are polymorphisms in the enzymes methylenetetrahydrofolate reductase (C677T) and cystathionine β-synthase (C699T, C1080T, and 844ins68). Although the frequency of hyperhomocysteinemia in our country is high, there is no evidence about the frequencies of these polymorphisms. Methods: We analyzed 80 healthy individuals from several regions in our country. We evaluated the fasting and post-oral methionine load plasma Hcy and the genotypes in order to obtain the allele frequencies of the polymorphisms C677T of methylenetetrahydrofolate reductase and C699T, C1080T, and 844ins68 of the cystathionine β-synthase. Results: No individual had deficiency of folic acid, vitamins B12, or B6, but 80% had post-oral methionine load hyperhomocysteinemia. We found a significant increase in the Hcy plasma concentration associated with age and gender. Only the polymorphism C1080T was significantly associated with hyperhomocysteinemia. Conclusion: There is an association between fasting and post-oral methionine load plasma Hcy concentrations with the allelic frequencies of the polymorphisms C669T, 844ins68, and C1080T of the cystathionine β-synthase and C667T of the methylenetetrahydrofolate reductase in healthy Mexican individuals. As compared with individuals with normal fasting or post-oral methionine load Hcy plasma levels, only C1080T was significantly associated with hyperhomocysteinemia.

Cheese ‘refinement’ with whey B-vitamin removal during precipitation potentially induces temporal ‘functional’ dietary shortage: homocysteine as a biomarker

Cheese ‘refinement’ with massive B-vitamin losses (≈70–84%) through whey removal during precipitation may potentially induce a temporal imbalance between protein/methionine load and episodic/shortage of nutrients critical for their metabolism,i.e.B6 and B12.

Abstract 3012: Significant Genome Wide Association Identified Between the Glycine N-Methyltransferase Gene (GNMT) and Post-Methionine Load Test Homocysteine Levels in the Vitamin Intervention for Stroke Prevention (VISP) Cohort

The Vitamin Intervention for Stroke Prevention (VISP) trial was a multi-center, controlled, double blinded clinical trial, designed to determine whether the daily intake of high dose folic acid, vitamins B6 and B12 reduced recurrent cerebral infarction. Baseline post-methionine load homocysteine levels were predictive of recurrent stroke risk in VISP. We have conducted a genome-wide association study (GWAS), investigating 2100 VISP stroke cases required to have homocysteine levels greater than the 25th percentile at enrolment. Using imputation with 1000 genomes and principal component analysis, we were able to detect an association of p≤6.70x10-17 for SNPs within, or flanking, the glycine N-methyltransferase (GNMT) gene and post-methionine load test homocysteine level. Change in homocysteine levels pre and post-methionine load test also resulted in significant GWAS scores in the chromosome 6 region (p = 2.54x10-23, rs7760250). GNMT catalyzes the conversion of S-adenosyl-L-methionine to S-adenosyl-L-homocysteine and sarcosine via the folate one-carbon metabolism pathway. In addition to being an essential component in the conversion of methionine to homocysteine, GNMT plays a significant role in the global epigenetic state as homocysteine is an important methyl donor. This region displays significant linkage disequilibrium, warranting close analysis of the entire GNMT locus in search of both rare and common variants. Cases who carry the minor allele haplotype at associated loci had a higher level of post-methionine load homocysteine (37.69µM/L) than those who carry the major allele haplotype (27.33µM/L), inferring functional differences due to GNMT variants. Taken together these data suggest a clear and important role for GNMT in post-methionine load test homocysteine level, epigenetic state and stroke risk.