Figure 5. Glycine is the limiting substrate in the synthesis of GSH in NAFLD .

• A
  Glycine is found to be the limiting substrate for the synthesis of glutathione (GSH) in subjects with NAFLD. Decreased de novo synthesis of serine has also been reported in subjects with NASH. The decreased plasma level of glycine, serine as well as other associated metabolites betaine and N‐acetylglycine in subjects with high HS is confirmed with the metabolomics study. In order to confirm model‐based predictions, serine was supplemented to the subjects with high HS since serine‐derived carbon can be converted to GSH to satisfy the increased demand for GSH in NAFLD. Blue arrows indicated downregulation whereas the red arrow indicates upregulation of the reactions. Green arrows indicate the significant correlation of the flux carried by the reactions and HS. [c], cytoplasm; [m], mitochondria.
• B–E
  The mRNA expressions of the (B) nicotinamide nucleotide transhydrogenase (NNT), (C) glutathione reductase (GSR), (D) glutamate–cysteine ligase, catalytic subunit (GCLC), and (E) glutamate–cysteine ligase, modifier subunit (GCLM) are measured in the livers obtained from 12 morbidly obese subjects who had undergone bariatric surgery and seven healthy individuals (mean ± SD). *P < 0.05; Student's t‐test.