Atypia of protein, lipid, and ion metabolism in tumors

Atypia of protein and nucleic acid metabolism

Protein atypia is based on the hyperactivity of the tumor cell genome. Due to a decrease in the level of nuclear repressors (in particular, histones and other suppressor proteins) and an increase in the enzymatic activity of DNA and RNA polymerases, intensification of DNA and RNA synthesis occurs. Increased oncogene expression ensures enhanced protein production, which implements growth, structural, and functional atypia.

The neoplasm functions as a "nitrogen trap", greedily capturing amino acids from the body for proteosynthesis reactions. A pronounced imbalance arises:

• The production of structural components, enzymes, and specific oncoproteins increases sharply.
• The synthesis of a number of other proteins (e.g., histones) decreases or completely stops.

Due to the modification of macromolecules, the antigenic profile of the tissue changes. On the one hand, this leads to the progression of tumor growth. On the other hand, it triggers mechanisms of antineoplastic defense, as tumor antigens alien to normal autologous cells appear in the body.

Carbohydrate metabolism: negative Pasteur effect

The tumor acts as a "carbohydrate trap", characterized by the active transport of glucose into the cell and its rapid utilization. Tissue respiration here provides only 10–50% of ATP resynthesis (versus 80–85% normally). Glycolysis becomes the main source of energy, and the incorporation of glucose into it increases 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 of this phenomenon lies in a decrease in the activity of cytoplasmic glycerophosphate dehydrogenase and the simultaneous activation of lactate dehydrogenase (LDH). The result is a massive accumulation of lactic acid (lactate). In addition, respiration regulation is impaired: upon oxygenation, glucose consumption is not activated.

In parallel, the pentose phosphate pathway (direct carbohydrate oxidation) is intensified. The biological significance of these shifts is enormous: they provide energy for plastic processes, increase cell survival under conditions of hypoxia and hypoglycemia, and supply pentoses for the construction of new nucleic acids.

Lipid and vitamin metabolism

The phenomenon of the "lipid trap" is formed. Blast cells significantly enhance the utilization of free fatty acids (FFAs) and cholesterol, activating the synthesis of their own lipid structures. The reason is an increase in the content and activity of lipid metabolism enzymes. At the same time, lipid peroxidation (LPO) processes intensify in the tissue against the background of the suppression or complete exhaustion of antioxidant defense factors.

All these changes are aimed at maximum energy and plastic support for actively dividing cells. An interesting clinical paradox: due to the fact that the tumor takes up huge amounts of lipids from the bloodstream, cancer patients often show a clinical correlation in the form of inhibition of atherogenesis in blood vessel walls.

The neoplasm also works as a "vitamin trap". Vitamins are needed by the tumor as coenzyme precursors and substrates to ensure growth. A striking example is the accumulation of fat-soluble vitamin E. Possessing antioxidant activity, it neutralizes free radicals, stabilizes cell membranes, and thereby increases the tumor's resistance to cytotoxic effects.

Disorders of ion and water metabolism

Compared to normal tissue, tumor tissue undergoes excessive accumulation of ions and water. Their normal ratio changes both in the cytosol and in the extracellular fluid.

Characteristic concentration shifts:

• Increase: potassium (K) and copper (Cu) accumulate inside the neoplasm.
• Decrease: calcium (Ca) levels drop. Some blastomas also show a decrease in the concentration of sodium (Na), magnesium (Mg), and zinc (Zn).

The reasons for such a pronounced ionic and water imbalance are diverse. Firstly, these are structural defects of the cell membranes themselves. Secondly, a malfunction of enzymes responsible for ion transport (the content and activity of Na+, K+-ATPase and Ca2+-ATPase decrease). Thirdly, the osmotic pressure inside tumor cells increases significantly. Finally, the constant destruction of cells in necrosis zones contributes its share.

Class and exam questions

What else to study on this topic

• Mechanisms of changes in the antigenic profile and activation of antineoplastic defense.
• The role of lactate dehydrogenase and glycerophosphate dehydrogenase in the Pasteur effect.
• The significance of the pentose phosphate pathway for the synthesis of nucleic acids in blastoma.
• Causes of the depletion of antioxidant defense factors during tumor growth.
• The impact of necrosis and osmotic pressure on water-ion imbalance.

Other topics in "Chapter 17. NEOPLASMS"

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