Table II.
Functions of lactate and lactate metabolism.
| Function | Description | (Refs.) |
|---|---|---|
| Energy regulation | Primary fuel in the TCA cycle. Supplementary sources of glucose | (48-52) |
| Regulation of fatty acid metabolism | Lactate promotes fatty acid synthesis by increasing the intracellular pool of acetyl- CoA as well as by increasing the activity of acetyl coenzyme A carboxylase (a key enzyme that regulates fatty acid synthesis). Furthermore, lactate induces CD4+ T cells to upregulate the expression of the lactate transporter SLC5A12, which mediates the uptake of lactate by CD4+ T cells, forming a positive feedback loop to increase the synthesis of fatty acids | (9,53) |
| Histone lactylation | Associated with lactate concentrations. Promotes the transition of macrophages from a pro-inflammatory phenotype to a reparative phenotype. HK2 promotes lactylation by acting on the H3K181a lactylation site, then promoting liver fibrosis. AK2 and lactylation of H3 histone contribute to the progression of HCC | (9,54-57) |
| Non-histone lactylation | By analyzing tumors and adjacent tissues from patients with HCC, 9,275 lactylation sites were identified, of which 9,256 were located on non-histone proteins. The role of non-histone lactylation has not been revealed in studies on liver diseases | (9,56) |
| LMRGs | Lactate metabolism contributes to tumor-induced immune suppression, a major obstacle to effective immune therapy. LMRGs can be used as predictors of tumor clinical prognosis. There are 66 LMRGs differentially expressed in HCC, mainly associated with metabolic processes and oxidative reactions. FKTN, PDSS1, PET117, PUS1, RARS1 and RNASEH1 were associated with the prognosis of HCC and were used to calculate the LMRG score; patients with a high LMRGS score had a poor prognosis, and the LMRGS score was positively associated with the expression of immune checkpoints such as PD-1. Further research is required to determine the predictive role of LMRGs | (58-61) |
HK2, hexokinase 2; AK2, adenosine kinase 2; HCC, hepatocellular carcinoma; PD-1, programmed death-1; LMRGs, lactate metabolism- related genes; TCA, tricarboxylic acid.