Figure 2.

The different regulations of glycolysis by enzymatic and nonenzymatic acetylations in different states of liver diseases. A) In hepatic metabolic syndrome and inflammation, glycolysis is regulated mainly by nonenzymatic acetylation in mitochondria. The acetylations of MDH2 and GOT2, which increase their enzymatic activity, promote the malate-aspartate shuttle and glycolytic activity. The acetylation of PDH, which inhibits its activity, leads to the glycolysis process toward lactate production. B) In cirrhosis and liver cancer, glycolysis is regulated by enzymatic acetylation largely in the nucleus and cytoplasm. Deacetylations enhance the glycolytic enzymatic activity of GLUT1, HK, and LDH-A. The deacetylation of GKRP by SIRT2 promotes its dissociation with GK, increasing glycolytic activity for cancer cell growth. PCAF and GCN5 acetylate PFKFB3, facilitating its accumulation in the cytoplasm and the activation of phosphofructokinase 1 (PFK1). The acetylations of GAPDH and PGK1 by PCAF and the acetylation of PGAM1 increase glycolytic activity, facilitating the rapid growth and tumorigenesis of hepatoma cells. The acetyltransferase p300 acetylates PKM2 at K433, promoting its nuclear import and protein kinase activity. The K305 acetylation of PKM2 by PCAF provokes its degradation, providing glycolytic intermediates for cancer cell growth. Meanwhile, the acetylations of transcription factors HIF-1α, PGC-1α, and FoxO and the histone H3K9 lead to the up-regulation of glycolytic genes like GLUT1, HK2, PKM2, and LDH-A. AC, acetyl group.