BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 8. VITAMINS

8.2. Fat-Soluble Vitamins

8.2.2. Vitamin A Group

Structure and physicochemical properties. The Vitamin A group includes vitamin A₁ (retinol) and vitamin A₂ (dehydroretinol). Vitamin A was discovered and isolated from fish Liver in the 1920s.

Vitamin A₁ and vitamin A₂ are polyprenyl alcohols containing 20 carbon atoms. Vitamin A₂ has half the biological activity of vitamin _A1. They are soluble in fats and organic Solvents such as chloroform, ether, benzene, and acetone. In its free state, retinol forms pale yellow crystals with a melting point of 63–64 °C. Upon Treatment with certain oxidizing agents or enzymatically, retinol is oxidized to an aldehyde, retinal. The product of further oxidation is retinoic acid (Fig. 8.3). The primary alcohol group of retinol can react with organic acids to form esters, which are more stable during storage and thermal Processing than the free vitamin.

Class="center">

Fig. 8.3. Structure of vitamin A

Vitamin A enters The Human Body in a free or esterified state with animal-derived products, or is synthesized from plant-derived carotenes. The Synthesis of the vitamin from carotenes occurs in animal and human organisms with the participation of carotinase (β-carotene dioxygenase), which catalyzes the oxidative Cleavage of the double bond in β-carotene to form an aldehyde (retinal) and requires the presence of Bile acids as emulsifiers. The system for converting carotenes into vitamin A is absent in newborns and certain animals.

In the human body and certain animals (cows, birds), un cleaved β-carotene can be absorbed in the intestine and stored. β-Carotene, as well as several other carotenoids that are not converted into vitamin A (such as lycopene), exhibit independent biological activity. Numerous studies consider carotenoids as potential agents capable of preventing The Development of various human pathologies, particularly cardiovascular and oncological diseases.

Biochemical Functions. The aldehyde form of the vitamin is converted into the alcohol form with the participation of an NADH-dependent retinaldehyde reductase. Retinol is transported in the Blood by retinol-binding protein (RBP), which belongs to the α₁-globulin fraction. This protein is rich in aromatic Amino Acids and forms a cone-shaped cavity that accommodates retinol. A decrease in vitamin intake leads to a drop in blood RBP levels. The protein also transports the vitamin from the liver to target Organs and assists its entry into The Cell. Receptors that interact with RBP are located on The Plasma Membrane. In the body, vitamin A is stored primarily as palmitic acid esters, predominantly in liver Cells.

Retinol is reversibly oxidized to retinal under METABOLISM/18.html">The Influence of an NAD-dependent retinaldehyde reductase. Retinal serves as the prosthetic group of the visual pigment rhodopsin, which is involved in photoreception. Rhodopsin is a conjugated protein, a glycoprotein, and the primary photosensitive pigment of retinal rods. The bond between the protein and retinal is formed via the aldehyde group of the vitamin and the free amino group of a Lysine residue in the protein molecule, resulting in a Schiff base (Fig. 8.4).

Light-activated rhodopsin initiates a cascade of reactions by interacting with Transducin, a member of the G-protein family. During this process, 11-cis-retinal is converted into all-trans-retinal and dissociates from the opsin protein.

All-trans-retinal is reduced to retinol and transported by retinol-binding protein to the epithelium, where it is esterified by lecithin:retinol acyltransferase, an enzyme that catalyzes The transfer of a fatty acid residue from lecithin to retinol. Part of the retinol is stored as esters, while the remainder, after isomerization to 11-cis-retinol, is released and oxidized to 11-cis-retinal.

Fig. 8.4. Transformation of rhodopsin

The oxidation of retinal to retinoic acid by retinal oxidase is an irreversible reaction. Retinoic acid is the hormonal form of vitamin A; its interaction with specific nuclear receptors in target Tissues triggers the synthesis of protein factors that regulate the proliferation and differentiation of Epithelial Tissues, such as the respiratory epithelium and gastric mucosa. The Transcription control mechanism is similar to that of Steroid Hormones. Receptors for retinoic acid are homologous to the steroid hormone receptor family and possess their own DNA-binding domain.

Vitamin requirement and natural occurrence. Vitamin A deficiency leads to night blindness (nyctalopia), xerophthalmia (drying of the cornea), delayed growth in children, weight loss, and general emaciation. Specific Skin lesions, pathological keratinization, and the development of follicular hyperkeratosis are observed. The epithelium of the entire digestive tract, respiratory tract, and Urinary System is also affected. Night blindness is among the earliest and most specific symptoms of vitamin A hypovitaminosis and avitaminosis. Cases of hypervitaminosis A have been described, manifesting as eye inflammation, hyperkeratosis, Hair loss, and headaches.

The plasma concentration of retinol is 30–40 µg/dL, and that of carotenoids is 80–230 µg/dL. The daily requirement for an adult is 1.5–2 mg (or 5,000–6,000 IU) of vitamin A or 2–5 mg of β-carotene. The primary dietary sources of vitamin A for humans include cod liver, beef liver, fatty fish, butter, and eggs. Red carrots, apricots, sea buckthorn, red bell peppers, pumpkin, and greens contain high amounts of carotene.