D-Glucose-6-phosphate is formed in cells when glucose is phosphorylated by hexokinase (or glucokinase) or by the conversion of glucose-1-phosphate by phosphoglucomutase, which is the first step of glycogen synthesis.[1] It is stored as glycogen when blood glucose levels are high. Disruption of D-glucose-6-phosphate activity leads to glycogen storage disease type I or von Gierke’s disease, a group of inherited metabolic diseases characterized by severe hypoglycemia, growth retardation, and hepatomegaly, due to accumulation of glycogen and fat in the liver.[2],[3] D-Glucose-6-phosphate is also the starting molecule of both glycolysis and the pentose phosphate pathways.[4] Because cancer cells adopt glycolysis as a major source of metabolic energy production, and the pentose phosphate pathway plays a role in helping glycolytic cancer cells to meet their anabolic demands, this compound can be used to study the progression of this process.[5]

Reference:

[1]. Berg, J.M., Tymoczko, J.L., and Stryer, L. Section 25.5 NAD+, FAD, and coenzyme A are formed from ATP. Biochemistry 5th Edition, (2002).

[2]. Cappellini, M.D., and Fiorelli, G. Glucose-6-phosphate dehydrogenase deficiency. Lancet 371(9606), 64-74 (2008).

[3]. Beutler, E. Glucose-6-phosphate dehydrogenase deficiency: A historical perspective. Blood 111(1), 16-24 (2008).

[4]. Gumaa, K.A., and McLean, P. The pentose phosphate pathway of glucose metabolism: Enzyme profiles and transient and steady-state content of intermediates of alternative pathways of glucose metabolism in Krebs ascites cells. Biochemistry Journal 115(5), 1009-1029 (1969).

[5]. Patra, K.C., and Hay, N. The pentose phosphate pathway and cancer. Trends Biochem. Sci. 39(8), 347-354 (2014).

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