FIGURE 1.

Mannose interferes with glucose metabolism in tumor cells with low expression of the MPI gene. Mannose and glucose are transported into cells by the same transporter (GLUT), and transformed by hexokinase (HK) into mannose-6-phosphate (M6P) and glucose-6-phosphate (G6P). In those tumor cells with low mannose phosphate isomerase (MPI) expression, the accumulation of M6P suppresses glucose phosphate isomerase (GPI) and other enzymes related to glucose metabolism, resulting in inhibition of glycolysis and in turn inhibition of the tricarboxylic acid cycle (TCA). In contrast, in tumor cells that express a high level of MPI, mannose could be used for glycolysis efficiently. Recent studies have found that Zn²⁺ is crucial for mannose phosphate isomerase (PMI) to exert enzymatic activity, and when ZIP10, a transporter of Zn²⁺, is knocked down, it causes the inactivation of MPI and makes tumor cells become mannose sensitive.