Metabolism of Mannose in Cultured Primary Rat Neurons

Abstract

Glucose is the main peripheral substrate for energy production in the brain. However, as other hexoses are present in blood and cerebrospinal fluid, we have investigated whether neurons have the potential to metabolize, in addition to glucose, also the hexoses mannose, fructose or galactose. Incubation of primary cerebellar granule neurons in the absence of glucose caused severe cell toxicity within 24 h, which could not be prevented by application of galactose or fructose, while the cells remained viable during incubation in the presence of either mannose or glucose. In addition, cultured neurons produced substantial and almost identical amounts of lactate after exposure to either glucose or mannose, while lactate production was low in the presence of fructose and hardly detectable during incubations without hexoses or with galactose as carbon source. Determination of the K values of hexokinase in lysates of cultured neurons for the hexoses revealed values in the micromolar range for mannose (32 ± 2 µM) and glucose (59 ± 10 µM) and in the millimolar range for fructose (4.4 ± 2.3 mM), demonstrating that mannose is efficiently phosphorylated by neuronal hexokinase. Finally, cultured neurons contained reasonable specific activity of the enzyme phosphomannose isomerase, which is required for isomerization of the hexokinase product mannose-6-phosphate into the glycolysis intermediate fructose-6-phosphate. These data demonstrate that cultured cerebellar granule neurons have the potential and express the required enzymes to efficiently metabolize mannose, while galactose and fructose serve at best poorly as extracellular carbon sources for neurons.

ZIP10 is a negative determinant for anti-tumor effect of mannose in thyroid cancer by activating phosphate mannose isomerase

“…Thus, it is reasonable to speculate that mannose kills thyroid cancer cells by this mechanism. When mannose enters into the cell, it transforms into M-6-P which accumulates when PMI enzyme activity is low, thereby decreasing cellular glycolytic levels [16,45]. As supported, our data showed that mannose treatment significantly suppressed the glycolysis of mannose-sensitive cells, while did not change that of mannose-insensitive cells.…”

Proteomics Study on the Cerebrospinal Fluid of Patients with Encephalitis

“…In the study, the KEGG annotation suggested that fructose and mannose metabolism, inositol phosphate metabolism, and Jak-STAT signaling pathway were the enriched signaling pathways among the EM, NED, and N groups. Notably, fructose and mannose metabolism and inositol monophosphatase have been identified in the CSF, , but no studies reported that it is associated with encephalitis. Additionally, the findings on Jak-STAT signaling pathway associated with the encephalitis were also supported by previous reports. − …”