Distribution of Glucose‐ 1,6‐Bisphosphate and IMP‐Activated Glucose Bisphosphatase in Brain and Retina

Abstract

The activity of glucose-1,6-bisphosphatase and the level of its substrate were measured in 16 gray areas and four fiber areas of mouse brain and 10 layers or sublayers of monkey retina. Because of the low activity of the enzyme and the small sample sizes, it was necessary to develop a method with two different amplification steps (overall amplification about 10(6]. The enzyme ranged in activity 100-fold from a low in monkey retina photoreceptor cells to a high in the pyramidal layer of the hippocampus. However, in gray areas of the brain proper the range was only about fourfold. This, together with its requirement for IMP, suggests that the enzyme has a widespread metabolic function related to states of increased neuronal activity. Glucose-1,6-bisphosphate levels varied from 80 to 960 mu mol/kg dry weight in different areas of mouse brain and from 44 to 200 mu mol/kg dry weight in different layers of monkey retina. In general, the glucose bisphosphate levels correlated positively with the bisphosphatase activities; however, the three areas with the highest enzyme concentrations did not fit this pattern.

Synthesis of Deoxyglucose‐1‐Phosphate, Deoxyglucose‐1,6‐Bisphosphate, and Other Metabolites of 2‐Deoxy‐D‐[14C]Glucose in Rat Brain In Vivo: Influence of Time and Tissue Glucose Level

“…The regional distribution of DG-1 ,6-P2 was not investigated in the present study, but it might parallel that of glucose-1,6-P,. The concentrations of glucose-1,6-P2 and the distributions of the glucose-1,6-P2 synthase and hydrolase vary widely throughout the brain (Yip et al, 1985(Yip et al, , 1988; no correlations between glucose-1 ,6-P2 levels and glucose-6-P, UDP-glucose, or phosphoglucomutase levels were found in various tissues (Passonneau et al, 1969). Regional heterogeneity of the "glucose-1,6-P, system" might explain the large range in the concentrations obtained for DG-1,6-P, compared with those for other labeled metabolites (see Table 2 and Fig.…”

Phosphoglycerates and Protein Phosphorylation: Identification of a Protein Substrate as Glucose‐1,6‐Bisphosphate Synthetase

“…The regional distribution of G1 ,6P2 synthetase in the brain coincides with that of G 1 ,6P2 and IMP-dependent G1,6P2 phosphatase (Yip et al, 1985). However, it does not parallel the distribution of phosphoglucomutase, and GI ,6P2 levels are much higher than the concentration required for the cofactor role in the phosphoglucomutase reaction (Yip et al, 1988).…”

Impaired glucose-1,6-biphosphate production due to bi-allelic PGM2L1 mutations is associated with a neurodevelopmental disorder

“…Furthermore the glucose-1,6-bisphosphate synthase activity of PGM2 is more powerfully inhibited by glucose-1,6-bisphosphate than that of PGM2L1, 11 indicating that PGM2L1 is more suitable to form the elevated concentrations of glucose-1,6-bisphosphate (about 100 nmol/g) that are found in mouse brain. 12,13,19 Again, we noted that reduction of the glucose-1,6-bisphosphate pool due to PMM1 overexpression did not appear to impact glycosylation of LAMP2. By contrast, LAMP2 glycosylation was markedly affected in neutrophils from individuals with G6PC3 deficiency, owing to a block in glucose metabolism due to accumulation of the hexokinase inhibitor 1,5-anhydroglucitol-6-phosphate (Figure 4D).…”

“…Furthermore the glucose-1,6-bisphosphate synthase activity of PGM2 is more powerfully inhibited by glucose-1,6-bisphosphate than that of PGM2L1, 11 indicating that PGM2L1 is more suitable to form the elevated concentrations of glucose-1,6-bisphosphate (about 100 nmol/g) that are found in mouse brain. 12 , 13 , 19 …”