Impact of Opioids on Cellular Metabolism: Implications for Metabolic Pathways Involved in Cancer

Changes in metabolites and enzymes of glycolysis, TCA, and glutaminolysis due to morphine treatment. There is consensus among studies regarding increased glucose transport into the cell, upregulation of LDH-A, and decreased expression/activity of PK, but the remaining steps of glycolysis display variable patterns of upregulation and downregulation by morphine. Three separate studies have found that morphine decreases malate dehydrogenase expression; however, the change in other enzymes and metabolites of the TCA vary within the literature. Glutamine metabolism, or glutaminolysis, directly feeds into the TCA through α-ketoglutarate production. Morphine and other opioids affect glutaminolysis metabolites and enzymes, yet conflicting findings exist about whether they amplify or diminish this metabolic pathway. Directionality of change in metabolite or protein is indicated in the brackets preceding study authorship. “+” indicates an increase in either activity, expression, or level, while “-” indicates a decrease in the aforementioned parameters. HK—hexokinase; GK—glucokinase; PGI—phosphoglucose isomerase; PFK—phosphofructokinase; ALDO—aldolase; DHAP—dihydroxyacetone phosphate; TPI—triosephosphate isomerase; GAPDH—glyceraldehyde-3-phosphate dehydrogenase; PGK—phosphoglycerate kinase; PGM—phosphoglycerate mutase; ENO—enolase; PK—pyruvate kinase; LDH-A—lactate dehydrogenase A; PD—pyruvate dehydrogenase; PC—pyruvate carboxylase; CS—citrate synthase; AH—aconitase or aconitate hydratase; IDH—isocitrate dehydrogenase; a-KGD—α-ketoglutarate dehydrogenase; SCoAS—succinyl CoA synthetase; SD—succinate dehydrogenase; FH—fumarase or fumarate hydratase; MD—malate dehydrogenase; GLS—glutaminase; GS—glutamine synthase; GDH—glutamate dehydrogenase (also known as glutamic acid decarboxylase); OXPHOS—oxidative phosphorylation; PPP—pentose phosphate pathway [,,,,,,,,,,,,,,,,,,,,,,,,,].

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Impact of Opioids on Cellular Metabolism: Implications for Metabolic Pathways Involved in Cancer. (2023) Doorsa Tarazi, et al. Pharmaceutics. 2023 Sep;15(9):2225. Figure: F2. All organisms Drosophila melanogaster Homo sapiens

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