Biological Chemistry - Berezov, T. T., & Korovkin, B. F. 1998

Vitamins
Fat-soluble vitamins
Vitamin A group

Vitamin A (retinol; anti-xerophthalmic vitamin) has been thoroughly studied. Three forms of vitamin A are known: A₁, A₂, and the cis-isomer of vitamin A₁, designated as neovitamin A. Chemically, retinol is a cyclic unsaturated monohydric alcohol consisting of a six-membered ring (ß-ionone), two isoprene residues, and a primary alcohol group.

Class="center">

Vitamin A₂ differs from vitamin A₁ by the presence of an additional double bond in the ß-ionone ring. All three forms of vitamin A exist as stereoisomers, although only some of them exhibit biological activity. Vitamins of the A group are readily soluble in fats and fat Solvents, such as benzene, chloroform, ether, and acetone. In the body, they are easily oxidized by specific Enzymes to form the corresponding cis- and trans-aldehydes known as retinens (retinals), i.e., vitamin A aldehydes; they can be stored in the Liver as more stable esters with acetic or palmitic acid.

Characteristic symptoms of Vitamin A deficiency in humans and animals include growth retardation, weight loss, general emaciation, and specific lesions of the Skin, mucous membranes, and eyes. The skin epithelium is affected first, manifesting as proliferation and pathological keratinization; this process is accompanied by follicular hyperkeratosis, severe scaling, and dryness of the skin. Consequently, secondary purulent and putrefactive processes develop. Vitamin A deficiency also affects the epithelium of the mucous membranes throughout the gastrointestinal tract, urogenital, and respiratory systems. A characteristic eye lesion is xerophthalmia, i.e., dryness of the cornea (from the Greek xeros meaning dry, and ophthalmos meaning eye) caused by obstruction of the tear duct, whose epithelium also undergoes keratinization. The Eyeball is no longer bathed in tear fluid, which is known to possess bacteriological properties. As a result, Conjunctivitis, edema, ulceration, and softening of the cornea develop. This complex of lesions is termed “keratomalacia” (from the Greek keras meaning horn, and malakia meaning softening); it develops very rapidly, sometimes within a few hours. The breakdown and softening of the cornea are associated with purulent processes, as putrefactive microorganisms rapidly proliferate on the corneal surface in the absence of tear fluid.

Among the earliest and most specific symptoms of vitamin A deficiency (hypovitaminosis A) is nyctalopia, or night blindness (hemeralopia). It manifests as a loss of visual acuity, specifically The ability to distinguish objects in twilight, although patients retain normal Vision during the day.

In addition to hypo- and avitaminosis, cases of hypervitaminosis A have been described following the consumption of liver from polar bears, seals, or walruses, which contains high amounts of free vitamin A. Characteristic manifestations of hypervitaminosis A include eye inflammation, hyperkeratosis, Hair loss, and general emaciation. As a rule, these are accompanied by loss of appetite, headaches, dyspeptic symptoms (nausea, vomiting), and insomnia. Hypervitaminosis can also develop in children as a result of ingesting large amounts of fish oil and vitamin A supplements. Acute hypervitaminosis has been reported in children following large doses of vitamin A, leading to elevated Blood levels.

Biological role. Vitamin A influences the barrier function of the skin and mucous membranes, the permeability of Cell membranes, and The Biosynthesis of their components, particularly certain Glycoproteins. The action of vitamin A in these cases is attributed to its putative involvement in Protein Synthesis. It is hypothesized that due to the presence of double bonds in its molecule, vitamin A may participate in redox reactions, as it is capable of forming peroxides, which in turn increase the oxidation rate of Other Compounds.

The Significance of vitamin A in The process of photoreception has been elucidated in greater detail. A crucial role in this physiological process is played by a specialized chromolipoprotein—the complex protein rhodopsin, or visual purple, which is the primary photosensitive pigment of the retina, specifically of the rod Cells located in its peripheral region. It has been established that rhodopsin consists of the lipoprotein opsin and a prosthetic group represented by the aldehyde of vitamin A1 (retinal); they are linked via the aldehyde group of the vitamin and the free ε-NH₂ group of a Lysine residue in the protein molecule, forming a Schiff base. Upon exposure to light, rhodopsin dissociates into the protein opsin and retinal; the latter undergoes a series of conformational changes and is converted into the trans-form. The transformation of light energy into visual excitation—a process whose molecular mechanism remains enigmatic to this day—is somehow linked to these conversions. In the dark, the reverse process occurs: the synthesis of rhodopsin, which requires the active aldehyde form, 11-cis-retinal. This can be synthesized from cis-retinol, trans-retinal, or the trans-form of vitamin A through the action of two specific enzymes, dehydrogenase and isomerase. The cyclic transformations of rhodopsin in the retina under light and dark conditions can be represented schematically as follows:

Thus, under METABOLISM/18.html">The Influence of a light quantum, rhodopsin decomposes via a series of intermediates (“orange” and “yellow” Proteins) into opsin and all-trans-retinal, which is the inactive aldehyde form of vitamin A. Evidence suggests that all-trans-retinal can be partially converted into active 11-cis-retinal under the influence of light (indicated by the dashed arrow in the diagram). However, the primary pathway for 11-cis-retinal production is the enzymatic Conversion of the trans-form of vitamin A into the cis-form (mediated by isomerase) followed by its oxidation in the presence of Alcohol dehydrogenase*.

It should be noted that similar visual cycles occur in both rods and cones. The retina has been shown to contain Three types of cone cells, each endowed with one of three color-sensitive pigments that absorb blue, green, and red light at maxima of 430, 540, and 575 nm, respectively. All three pigments, designated iodopsins, also contain 11-cis-retinal but differ in The Nature of the opsin moiety (cone opsin types). Certain forms of color blindness (daltonism) are caused by the Congenital absence of synthesis of one of the three cone opsin types or by the synthesis of a defective opsin (resulting in red-green color confusion).

Natural occurrence and daily requirement. Vitamin A is widespread in nature. The richest sources of this vitamin in animal products are beef and pork liver, egg yolk, whole milk, butter, sour cream, and heavy cream. Free vitamin A is particularly abundant in the liver oils of sea bass, cod, and halibut; specifically, the vitamin A content in sea bass liver oil reaches up to 35%. Dietary sources of vitamin A for humans also include red-fleshed vegetables (carrots, tomatoes, peppers, etc.), in which vitamin A is present in the form of provitamins—carotenes, first isolated from carrots (from the Latin carota). Three types of carotenes are known: α-, β-, and γ-carotenes, which differ in chemical Structure and biological activity. β-Carotene exhibits the highest biological activity because it contains two β-ionone rings, yielding two molecules of vitamin A upon Cleavage in the body.

* An absorbed photon triggers The formation of a series of photolysis intermediates differing in absorption spectra within just a few pico(milli)seconds [prelumirhodopsin (543 nm), lumirhodopsin (497 nm), metarhodopsin I (480 nm), and metarhodopsin II (380 nm)]; the latter is completely hydrolyzed into opsin and trans-retinal within a few seconds.

The oxidative Cleavage of α- and γ-carotenes yields only one molecule of vitamin A each, as these provitamins contain a single β-ionone ring. The cleavage of carotenes into vitamin A molecules occurs predominantly in the intestine through the action of the specific enzyme β-carotene dioxygenase (though a similar transformation in the liver cannot be excluded) in the presence of molecular oxygen. This process generates two molecules of retinal, which are subsequently reduced to vitamin A by a specific intestinal reductase. The absorption efficiency of carotenes and free vitamin A depends both on dietary fat content and on the presence of free Bile acids, which are absolutely essential compounds for the absorption of lipid Digestion products.

The daily requirement for an adult averages 2.7 mg of vitamin A or 2 to 5 mg of β-carotene. In humans, the primary organ where vitamin A is partially stored as a reserve is the liver. Under normal conditions, it contains about 20 mg of this vitamin per 100 g of tissue.