References
SE, GS, SAH
SIDE EFFECTS
Glutathione redox cycle. Glutathione is primarily synthesized in the liver. Oxidized glutathione (GSSG) is then reduced via glutathione reductase and nicotinamide adenine dinucleotide phosphate (NADPH) into reduced glutathione (GSH). GSH is a major antioxidant in the body that primarily acts to eliminate reactive oxygen species (ROS). A major source of ROS is from oxidative phosphorylation in mitochondria. Mitochondrial GSH (mGSH) plays an important role in maintaining the redox balance in the body.Methionine cycle, transsulfuration pathway, and production of glutathione. The top portion of the figure depicts the methionine pathway, in which methionine is catalyzed by methionine adenosyltransferase (MAT) to form S-adenosyl-methionine (SAM), which is a primary methyl donor in the body. SAM is converted to S-adenosylhomocysteine (SAH) after donating its methyl group, and later hydrolyzed to form homocysteine. Homocysteine can be remethylated to form methionine using betaine-homocysteine methyltransferase (BHMT), thus closing the methionine cycle. The transsulfuration pathway depicted starts with the condensation of homocysteine and serine using cystathionine-β-synthase (rate-limiting step) to form cystathionine. Cystathionine is further hydrolyzed by cystathionine-γ-lyase to produce cysteine, which is further used to produce taurine and pyruvate. Glutathione production starts with cysteine, which is combined with glutamate via the enzyme glutamate cysteine ligase (GCL). The resulting γ-glutamylcysteine is then converted to reduced glutathione (GSH) via glutathione synthetase (GS). GSH is used for the reduction of ROS via glutathione peroxidase (GPX) and the resulting glutathione disulfide (GSSG) can be converted back to GSH via glutathione reductase (GR).Patient demographics for study sample.Comparison of baseline (pre) and post-treatment (post) oxidative lab values.Baseline Social Responsive Scale (SRS).Comparison of Aberrant Behavior Checklist (ABC) at baseline and post-treatment.Mean difference and clinical significance of Aberrant Behavior Checklist (ABC) pre- and post-treatment scores.Side effects of glutathione during course of treatment.Comparison of pre- and post-treatment CGI scores. Note: TE, therapeutic effect; SE, side effects.