Glycolysis is downregulated in idiopathic pulmonary fibrosis (IPF) lungs, with possible shuttling of intermediates to the sorbitol and pentose phosphate.

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Glycolysis is downregulated in idiopathic pulmonary fibrosis (IPF) lungs, with possible shuttling of intermediates to the sorbitol and pentose phosphate pathways. Glycolysis is downregulated in idiopathic pulmonary fibrosis (IPF) lungs, with possible shuttling of intermediates to the sorbitol and pentose phosphate pathways. (A) Analysis of gene expression for key enzymes of glycolysis. Gene-encoding enzymes, including the genes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), phosphofructokinase (PFK), phosphoglycerate mutase 1 (PGAM1), PGAM4, glucose-6-phosphatase catalytic subunit 3 (G6PC3) and SLC2A4RG, were significantly downregulated in IPF compared with normal suggesting a decreased rate of glycolysis (p<0.05). (B) The classical glycolysis/pentose/energy pathways are shown. (C) Data for metabolic intermediates in the normal lung (NL) are shown in green boxes, and data for IPF are represented in purple boxes. Levels of glycolytic intermediates fructose 1,6-bisphosphate (fructose 1,6-BP) and phosphoenolpyruate were significantly decreased in IPF, suggesting decreased glycolysis. Fructose levels were significantly increased, whereas sorbitol levels showed an upwards trend in IPF, possibly indicating shuttling of glycolytic intermediates towards the sorbitol pathway. The y-axis label of metabolic changes is shown as counts×106 and the y-axis label for gene expression encoding enzymes as fold changes of relative RNA levels of enzymes. DHAP, dihydroxyacetone phosphate. Yidan D Zhao et al. BMJ Open Resp Res 2017;4:e000183 ©2017 by British Thoracic Society