Figure 1.

Schematic representation of altered amino acids metabolism in myofibroblast of idiopathic pulmonary fibrosis (IPF). Glutamine is converted to glutamate and then to α-ketoglutarate (α-KG) to enter the tricarboxylic acid (TCA) cycle, thus providing enough adenosine triphosphate (ATP) to sustain cell growth, proliferation, and collagen production. Transforming growth factor β1 (TGF-β1) activates the activating transcription factor 4-mechanistic target of rapamycin complex 1 (ATF4-mTORC1) axis, increasing glycine biosynthesis, stimulating glucose transporter 1 (GLUT1) production, and allowing subsequent glycolysis needed for collagen production. Upregulation of arginine by-products and arginase-1 (Arg-1) has been linked to collagen synthesis through increased proline production.