Figure 4.

Increased antioxidant defense in EC relative to VP linked to glutathione and one-carbon metabolism

(A) A schematic presentation of methionine metabolism that is linked to transsulfuration pathway, one-carbon metabolism, and glutathione metabolism. Methionine is transformed into S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) and finally converted into homocysteine, which is also connected to one-carbon metabolism. In the transsulfuration pathway, cysteine and homocysteine are interconverted through the intermediate homocysteine. Cysteine can give rise to the antioxidants taurine and hypotaurine and it is also part of de novo glutathione synthesis. As glutamate is one of the three peptides glutathione (GSH) constitutes of, there is a link to the gamma-glutamyl cycle. By reducing reactive oxygen species (ROS), GSH is transformed to its oxidized form GSSG and GSSG can be reverted to reduced GSH by the enzyme glutathione reductase. Boxes in neighborhood of a metabolite indicate that the respective metabolite was detected and quantified in all our samples. Box 1 shows comparison between EC and HC, box 2 between VP and HC, and box 3 between EC and VP. A gray box presents non-significant difference in plasma levels, red presents fold-change greater than one (with p value<0.05), and green fold-change smaller than one (with p value<0.05).

(B) Heatmap representing levels of metabolites that are part of amino acids; methionine, cysteine, SAM, and taurine metabolism; and glutathione metabolism. Samples are grouped according to study group (EC, HC, VP). Metabolites written in red are part of the scheme shown under (A). Color depictures increasing log2 levels from blue via green to yellow. Data shown include samples of HC (n = 12), EC (n = 13), and VP (n = 16).

See also Figure S5 and Table S1 for differences in respective metabolite levels between study groups.