Plasma free amino acids (PFAAs) are sensitive metabolites indicative of cancer related critical illness. Changes in protein metabolism, as reflected by the PFAA profile, may represent a new diagnostic tool for cancer. High-mobility group B1 (HMGB1) is a multifunctional protein, which associated with cancer development, progression and metastasis with suppression of anti-cancer immunity by induction of monocyte-linage cells. HMGB1 played an important role in cause of PFAA alteration. HMGB1 induced degradation in the skeletal muscle through inhibiting glycogen utilization by pyruvate kinase suppression and activation of autophagy by dephosphorylating of mammalian target of rapamycin (mTOR). Autophagy increased free glutamine in muscle cells, which utilized glutamine as energy source through glutaminolysis-tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Glutamine was also released into the blood and taken by cancer cells, which utilized glutamine as energy source through glutaminolysis-partial use of TCA cycle-lactate fermentation. Thus, HMGB1-induced dysregulation of metabolism in the muscle causes the alteration of the PFAA profile.
Yi Luo, Junya Yoneda, Takamitsu Sasaki, Isao Kawahara, Kei Goto, Kiyomu Fujii, Hitoshi Ohmori and Hiroki Kuniyasu
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