Protein and Nucleic Acid Metabolism Atypism
Protein atypism is rooted in the hyperreactivity of the tumor cell genome. Due to a decrease in nuclear repressors (such as histones and other tumor suppressor proteins) and an increase in the enzymatic activity of DNA and RNA polymerases, there is an intensification of DNA and RNA synthesis. Upregulated oncogene expression ensures enhanced protein production, driving atypism of growth, structure, and function.
The neoplasm functions as a 'nitrogen trap,' greedily capturing amino acids from the body for proteosynthesis reactions. A marked imbalance occurs:
- The production of structural components, enzymes, and specific oncoproteins increases sharply.
- The synthesis of certain other proteins (e.g., histones) decreases or completely ceases.
Modification of macromolecules alters the antigenic profile of the tissue. On one hand, this leads to tumor growth progression. On the other hand, it triggers anti-tumor defense mechanisms as tumor-associated antigens appear that are foreign to normal autologous cells.
Carbohydrate Metabolism: Negative Pasteur Effect
The tumor acts as a 'carbohydrate trap,' characterized by active glucose transport into the cell and its rapid utilization. Tissue respiration provides only 10–50% of ATP resynthesis here (versus 80–85% normally). Glycolysis becomes the primary energy source, with glucose incorporation into glycolytic pathways increasing manifold.
A key feature of blastoma carbohydrate metabolism is the negative Pasteur effect. In healthy tissues, oxygen inhibits glycolysis, but in tumor cells, glucose breakdown continues even under aerobic conditions. The mechanism behind this phenomenon lies in decreased cytoplasmic glycerol-3-phosphate dehydrogenase activity coupled with the simultaneous activation of lactate dehydrogenase (LDH). The result is a massive accumulation of lactic acid (lactate). Furthermore, respiratory regulation is impaired: oxygenation fails to suppress glucose consumption.
Concurrently, the pentose phosphate pathway (direct carbohydrate oxidation) is intensified. The biological significance of these shifts is enormous: they supply energy for plastic processes, increase cell survival under hypoxia and hypoglycemia, and provide pentoses for synthesizing new nucleic acids.
Lipid and Vitamin Metabolism
A 'lipid trap' phenomenon develops. Blast cells significantly enhance their utilization of free fatty acids (FFAs) and cholesterol, activating the synthesis of their own lipid structures. This is driven by increased levels and activity of lipid metabolism enzymes. Simultaneously, lipid peroxidation (LPO) processes intensify within the tissue against a background of suppressed or fully depleted antioxidant defense systems.
All these changes are directed toward maximum energy and plastic support for actively dividing cells. An interesting clinical paradox arises: because the tumor extracts huge volumes of lipids from the bloodstream, cancer patients frequently exhibit inhibition of atherogenesis in arterial walls.
The neoplasm also functions as a 'vitamin trap.' Vitamins are required by the tumor as coenzyme precursors and substrates to support growth. A prime example is the accumulation of lipid-soluble vitamin E. Exhibiting antioxidant activity, it neutralizes free radicals, stabilizes cell membranes, and thereby increases tumor resistance to cytotoxic agents.
Water and Electrolyte Disturbances
Compared to normal tissue, tumor tissue exhibits an excessive accumulation of ions and water. Their normal ratios are altered in both the cytosol and the extracellular fluid.
Characteristic concentration shifts:
- Increase: Potassium ($K$) and copper ($Cu$) accumulate inside the neoplasm.
- Decrease: Calcium ($Ca$) levels drop. In some blastomas, reductions in sodium ($Na$), magnesium ($Mg$), and zinc ($Zn$) concentrations are also noted.
Causes of this pronounced ion and water imbalance are diverse. First, there are structural defects in the cell membranes themselves. Second, there is impaired function of ion-transporting enzymes (the content and activity of $Na^+, K^+$-ATPase and $Ca^{2+}$-ATPase are reduced). Third, osmotic pressure inside tumor cells is significantly elevated. Finally, constant cell destruction in necrotic zones contributes to the imbalance.