Biochemistry and Molecular Biology - Belyasova N.A. 2002

Metabolism. Processes Requiring Energy Input
Biological Role and Biosynthesis of Vitamins
Fat-Soluble Vitamins

Fat-soluble Vitamins include vitamins A, D, E, and K, as well as Q and F, with the latter two frequently classified as Vitamin-like compounds. In terms of their chemical Structure, all these vitamins except F are Isoprenoids.

Isoprenoids (Terpenes) constitute a vast group of compounds that share common Cytology/cytology/16.html">Early stages of Biosynthesis involving a five-carbon branched unsaturated hydrocarbon—isoprene (2-methylbuta-1,3-diene)—as a precursor. In addition to the aforementioned vitamins, isoprenoids include carotenoids, sterols, rubber, phytol (a constituent of chlorophyll), and many Other Compounds.

Fat-soluble vitamins perform non-coenzyme Functions in the body.

Vitamin A (retinol). This vitamin exists in the form of two vitamers (chemically similar forms of a vitamin with distinct physiological activities)—A₁ (retinol) and A₂ (dehydroretinol). Dehydroretinol differs from retinol by the presence of a double bond between the 3rd and 4th carbon atoms in the six-membered ring (Fig. 17.1). Furthermore, vitamin A (an alcohol) readily undergoes oxidation to yield a family of retinoids, which includes retinal and retinoic acid (Fig. 17.1). Retinal functions as a visual pigment (Chapter 13), whereas retinoic acid acts as a growth factor, participating in Bone tissue development and maintaining the normal secretory function of mucous membranes.

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Fig. 17.1. Structures of Various Forms of vitamin A (explanations in the text)

The Biological Role of vitamin A and its derivatives involves The regulation of Cell Differentiation, the Prevention of epithelial keratinization, and participation in protein and Lipid METABOLISM, oxidative processes, and membrane permeability regulation. The daily requirement for an adult is 1 mg. Vitamin A deficiency leads to loss of visual acuity and night blindness (nyctalopia), damage to Epithelial Tissues and mucous membranes, growth retardation, weight loss, and impairment of The Nervous system, Adrenal Glands, and Testes.

It is worth noting that vitamin A deficiency is particularly hazardous for children, whereas adults can store this vitamin by forming esters with palmitic acid. In this stored form, retinol is more stable and accumulates in the Liver in amounts sufficient to meet requirements for up to 2 years.

Sources of vitamin A include animal products (especially the liver of marine animals and fish), as well as plant-based foods containing carotenoids. In The Human Body, carotenes serve as precursors (provitamins) from which vitamin A is synthesized.

In turn, ß-carotene is found in fresh vegetables and fruits, being particularly abundant in carrots and pumpkins. Additionally, carotenoids are synthesized by many microorganisms, including microalgae, Yeasts, filamentous Fungi, actinomycetes, and mycobacteria.

The biosynthesis of carotenoids, much like that of other isoprenoids, proceeds from acetyl-CoA through several stages and obeys the "isoprene rule" first formulated by the Swiss chemist L. Ruzicka. According to this rule, the synthesis obligatorily involves isoprene units and the following transformations:

1) formation of mevalonate from acetyl-CoA or leucine; 2) phosphorylation, dehydration, and decarboxylation of mevalonate yielding "active isoprene"—isopentenyl pyrophosphate; Condensation of isoprene units to form linear molecules of varying lengths; 3) cyclization of segments of the linear isoprenoid molecules; and 4) Modification of the cyclic structures.

The MAIN STAGES OF ß-carotene biosynthesis, which follows the Ruzicka rule, are illustrated in Figures 17.2 and 17.3.

Fig. 17.2. Synthesis of phytoene, the colorless precursor of pigmented carotenoids (C40 linear molecule)

Fig. 17.3. Synthesis of pigmented derivatives from phytoene, leading to The formation of ß-carotene and retinol

It should be noted that farnesyl pyrophosphate—an intermediate formed during the early stages of carotenoid biosynthesis (Fig. 17.2)—serves as a precursor for the synthesis of sterols (Chapter 15) and vitamin Q.

Phytoene, a linear 40-carbon molecule composed of repeating isoprene units, undergoes four successive dehydrogenation steps, resulting in the Introduction of four additional double bonds (yielding lycopene, the red pigment of tomatoes), and is subsequently cyclized into ß-carotene via a g-carotene intermediate (Fig. 17.3).

In The Liver and intestinal mucosa Cells of animals and humans, ß-carotene can undergo oxidative Cleavage to yield two molecules of retinol (Fig. 17.3).

Vitamin D (calciferol). Like vitamin A, calciferol exists as multiple vitamers, with vitamins D₂ and D₃ being the most widespread. Vitamin D₂ is derived from the provitamin ergosterol, whereas vitamin D₃ is produced from a modified Cholesterol derivative (7-dehydrocholesterol) under the action of solar radiation. Ultraviolet irradiation causes the cleavage of ring B in the sterol molecule by breaking the bond between the 9th and 10th carbon atoms (Fig. 17.4; compare with Fig. 4.4). In animals, this reaction takes place in Skin cells.

Because provitamins (sterols) can be synthesized endogenously in animals and humans (Chapter 15) as well as obtained from the diet, Vitamin D deficiency in adults is rare (occurring primarily with inadequate sun exposure or, occasionally, due to hereditary disorders). However, in children—whose bodies undergo intensive membranogenesis and rapid development of tissues, bone, and muscular systems—vitamin D insufficiency is frequently observed and can lead to Rickets, a condition associated with impaired bone mineralization.

Fig. 17.4. Structures of vitamins D, E, and K

Vitamin D participates in Lipid Peroxidation reactions; furthermore, vitamer D₃ is hydroxylated in the liver and Kidneys of animals to form the hormone calcitriol (1,25-dihydroxycholecalciferol). Calcitriol, acting alongside two Other Hormones, is involved in the Regulation of Calcium Homeostasis in the body. Specifically, calcitriol stimulates intestinal calcium absorption and its incorporation into bone tissue.

Foods rich in vitamin D₃ include fish oil, butter, chicken egg yolks, animal liver, and milk. The daily requirement for vitamin D is 0.01 mg. Ensuring an adequate intake of vitamin D is essential for farm animals, particularly chickens and cows, due to their exceptionally high calcium metabolism. Vitamin D (primarily ergocalciferol) is obtained by ultraviolet irradiation of Yeast or fungal biomass, or previously isolated ergosterol.

Vitamin E (tocopherol). This term encompasses a group of vitamers synthesized by plants. The most common are α- (Fig. 17.4), β-, and γ-tocopherols, which differ in the number and position of methyl groups on the benzene ring. Tocopherols exhibit antioxidant activity toward unsaturated Lipids, acting as reducing agents that readily react with oxidizing substances (such as peroxide radicals) and thus protect other molecules from oxidation. This property of tocopherols is most pronounced with respect to Membrane Lipids, which stabilizes their functions and, consequently, the biochemical processes associated with membrane activity.

Additionally, tocopherols are involved in regulating enzyme synthesis and controlling the metabolism and function of ubiquinone, a component of the Respiratory Chain.

The highest concentrations of vitamin E are found in wheat germ and vegetable oils, as well as in leafy greens and cabbage. The daily human requirement for this vitamin is 10 mg.

A dietary deficiency of vitamin E can impair Embryogenesis, lead to reproductive disorders, and cause muscular dystrophy, limb paralysis, and Spinal Cord degeneration, among other conditions. However, vitamin E deficiency is quite rare in A balanced diet because vitamin E can be stored in animal tissues, compensating for insufficient dietary tocopherol intake for several months.

Vitamin K (phylloquinone). The Vitamin K group includes compounds with molecular structures similar to vitamin K₁, or phylloquinone (Fig. 17.4). Furthermore, vitamin K₂ (menaquinones), which differ in The structure of their side chain, as well as many naphthoquinone derivatives, are widespread.

Vitamin K is an antihemorrhagic factor that promotes and accelerates Blood clotting. Specifically, phylloquinone participates in the carboxylation of glutamic acid residues in Blood Plasma Proteins. In plants and microorganisms, menaquinones are involved in the redox processes of Oxidative Phosphorylation AND Photophosphorylation.

The daily requirement for vitamin K in adults is 0.08 mg. Large quantities of this vitamin are present in the green parts and fruits of plants (tomatoes, cabbage, pumpkin), as well as in animal liver. Additionally, vitamin K is synthesized by the intestinal microflora; therefore, vitamin K deficiency is typically observed only in newborns.

Vitamin Q (ubiquinone). Quinones, including ubiquinone (Q₁₀), were already discussed in Chapter 12 as Coenzymes. However, there is good reason to classify ubiquinones as Vitamin-like substances because, although they are synthesized in Human and Animal organisms, certain diseases are known to be cured by the administration of Q₁₀. Examples include anemia or Bone Marrow disorders caused by protein malnutrition in children.

Ubiquinones are known to participate in electron transport during Respiration and Photosynthesis, and they also exert an antioxidant effect within membranes that is even more potent than that of tocopherol.

Ubiquinones are synthesized by all organisms except for certain Bacteria. The precursor of the aromatic ring is $p$-hydroxybenzoic acid, which in animals is synthesized from Tyrosine and phenylalanine; thus, animal ubiquinone synthesis depends on dietary protein. The isoprenoid side chain of ubiquinones is synthesized according to Ruzicka's rule. Rich sources of ubiquinones include tissues with high rates of redox metabolism: The Heart Muscle, liver, and brown adipose tissue.

Vitamin F (Essential Fatty acids). Polyunsaturated fatty acids—linoleic (18:2), linolenic (18:3), and arachidonic (20:4)—cannot be synthesized de novo in the human body and must be obtained from the diet. On this basis, it has been proposed to classify them as vitamins. Arachidonic acid, however, can be formed from linoleic and linolenic acids. It serves as a precursor to a large group of local signaling molecules known as Eicosanoids. Eicosanoids perform vital functions: they participate in the release of Intracellular Signaling molecules, regulate smooth Muscle contraction, and influence bone metabolism, as well as the nervous and immune systems.

Vitamin F has been implicated in the Regulation of Lipid Metabolism, and its role in promoting The excretion of excess cholesterol from the body has been identified. There is also evidence indicating that Unsaturated fatty acids have a beneficial effect on the condition of the skin and Hair. However, clinical vitamin F deficiency in humans has not been described.