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The TME represents a stress-loaded milieu characterized by low pH, high lactate, hypoxia, an increased NADH/NAD + ratio, and pro-inflammatory signals ( 4.3 Suppression of energy metabolism Acidic pH and an elevated NADH/NAD + ratio inhibit key glycolytic enzymes—phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and pyruvate kinase (PK)—thereby restricting ATP production ( 4.4 Ion permeability and volume regulation Maintenance of ion homeostasis in erythrocytes is ensured by membrane pump systems, particularly Na + /K + -ATPase and Ca 2+ -ATPase

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