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Fig. 1 | Nutrition & Metabolism

Fig. 1

From: Press-pulse: a novel therapeutic strategy for the metabolic management of cancer

Fig. 1

Targeting Glucose and Glutamine for the Metabolic Management of Cancer. Cancer cells are largely dependent on glucose and glutamine for survival and growth. Energy through fermentation metabolism (substrate level phosphorylations, SLP) in glycolysis and the tricarboxylic acid cycle (TCA) will compensate for reduced energy through oxidative phosphorylation (OxPhos) that occurs in tumor cells. The yellow ovals indicate the three source of cellular ATP production. Glucose carbons can be used for both the glycolytic and pentose phosphate (PPP) pathways to supply ATP and precursors for lipid and nucleotide synthesis, as well as for glutathione production. Glutamine provides its amide nitrogen for ammonia and nucleotide synthesis. The glutamine-derived glutamate provides anapleurotic carbons to the TCA cycle through α-KG for protein synthesis while also providing ATP through TCA cycle SLP. TCA cycle substrate level phosphorylation through the succinate thiokinase reaction can generate significant cellular ATP under hypoxia especially in tumor cells with defective respiration [78]. The glutamine-derived glutamate is also used for glutathione production that protects tumor cells from oxidative stress. Glucose and glutamine targeting will thus make cancer cells vulnerable to oxidative stress therapies. The simultaneous targeting of glucose and glutamine through the press-pulse therapeutic strategy will starve tumor cells of energy production while blocking their ability to synthesize proteins, lipids, and nucleotides. Glucose and glutamine can also be generated internally through the lysosomal digestion of phagocytosed glycoconjugates and proteins (see text). An elevation of non-fermentable ketone bodies through, calorie restriction, ketogenic diets, or supplementation will provide normal cells with an alternative energy source to glucose while also protecting them from oxidative stress. Ghost mitochondria are those containing little or no inner mitochondrial membranes (cristae), which are essential for normal OxPhos function [67, 282, 283]

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