Vitamins and minerals

Metabolic disorders in liver pathologies

The liver plays a central role in micronutrient metabolism. In liver failure, significant and diverse disorders of mineral metabolism develop, including copper, chromium, and iron. A classic example of mineral imbalance is hereditary hemochromatosis, in which excess iron accumulates in hepatocytes, eventually provoking hepatomegaly and cirrhosis.

In addition, vitamin metabolism is severely impaired in liver diseases:

• Decreased provitamin transformation: precursors fail to convert into their active forms (e.g., the conversion of $\beta$-carotene to vitamin A is blocked).
• Inhibited coenzyme synthesis: the liver loses its full capacity to form thiamine pyrophosphate from vitamin B₁, flavin mononucleotide and flavin adenine dinucleotide (FMN and FAD) from vitamin B₂, pyridoxal-5-phosphate from vitamin B₆, and coenzyme A from pantothenic acid.

Natural antioxidants and their classes

Many vitamins and vitamin-like substances act as low-molecular-weight non-enzymatic antioxidants. They protect cells against lipid peroxidation (LPO) and free radicals. The pathogenetic rationale for their use, including in the treatment of atherosclerosis, is the significant role of free-radical processes in the development of the disease.

Main representatives of natural antioxidants:

• Tocopherols (vitamin E): potent cell membrane protectors that inhibit radical formation and prevent lipid peroxidation.
• Ascorbic acid (vitamin C): participates in redox reactions. It reversibly converts from the reduced form (containing an en-diol group) to oxidized dehydroascorbic acid (with two keto groups). This process is accompanied by the release or uptake of two protons (2H⁺) and two electrons (2e⁻).
• Carotenoids and vitamin A (Retinol): reduce cellular oxygen concentration by directing it toward oxidation and phosphorylation processes.
• Riboflavin (vitamin B₂): as a precursor to FAD and FMN, indirectly supports the antioxidant status through redox reactions.
• Vitamin D: its primary function is the regulation of calcium metabolism, but the substance is also used in the combination therapy of atherosclerosis.

Links of the antioxidant system (AOS)

Cellular antioxidant defense operates at several levels, where different substances perform specific tasks:

1. Anti-radical link: directly scavenges free radicals. Vitamin E and mannitol operate here.
2. Anti-oxygen link: utilizes excess oxygen. Includes carotenoids, vitamin A, and riboflavin.
3. Anti-peroxide link: inactivates already formed lipid hydroperoxides. A typical representative of this link is serotonin.

Also playing a crucial role are glutathione-containing substances, which function as a non-enzymatic defense factor in tandem with the enzyme glutathione peroxidase.

Other low-molecular-weight antioxidants

In addition to classical vitamins, natural low-molecular-weight antioxidants include:

• Flavonoids: plant-derived polyphenolic compounds. Their main feature is the ability to scavenge free radicals and chelate (bind) transition metal ions.
• Uric acid: an endogenous water-soluble antioxidant circulating in blood plasma.
• Ubiquinone (coenzyme Q10): a fat-soluble cell membrane protector and a vital component of the respiratory chain.
• Melatonin: a compound with pronounced anti-radical activity.

In the context of pharmacotherapy, all these substances are classified into direct (directly bind and inactivate radicals) and indirect (stimulate the body's own antioxidant system).

Class and exam questions

What else to study on this topic

• Mechanisms of lipid peroxidation (LPO) in atherosclerosis.
• The enzymatic link of the antioxidant system (glutathione peroxidase).
• Chemical structure and reversible transitions of ascorbic acid.
• The role of coenzyme Q10 in the mitochondrial respiratory chain.
• Pathogenesis of hereditary hemochromatosis.

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.