Vitamins PDF

12/31/2024 PUBLIC / CYHOEDDUS I. Vitamins, Overview: Vitamins are chemically unrelated organic compounds that cannot be synthesized in adequate quantities by humans and, therefore, must be sup...

12/31/2024 PUBLIC / CYHOEDDUS I. Vitamins, Overview: Vitamins are chemically unrelated organic compounds that cannot be synthesized in adequate quantities by humans and, therefore, must be supplied by the diet. Nine vitamins (folic acid, cobalamin, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin, and pantothenic acid) are classified as water-soluble, whereas four vitamins (vitamins A, D, K, and E) are termed fat-soluble. Vitamins are required to perform specific cellular functions, for example, many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. 1 PUBLIC / CYHOEDDUS 2 1  12/31/2024 PUBLIC / CYHOEDDUS I. fat soluble vitamin In contrast to the water-soluble vitamins, only one fat soluble vitamin (vitamin K) has a coenzyme function. These vitamins are released, absorbed, and transported with the fat of the diet. They are not readily excreted in the urine, and significant quantities are stored in the liver and adipose tissue. In fact, consumption of vitamins A and D in excess of the recommended dietary allowances can lead to accumulation of toxic quantities of these compounds 3 PUBLIC / CYHOEDDUS Vitamin D A group of structurally related compounds that play a role in the regulation of calcium and phosphorus metabolism – the most abundant form in the circulatory system is vitamin D3 (Cholecalciferol) which is formed in the skin from 7-dehydrocholesterol – Vit D3 is converted into the active form in two steps:  the first at the liver  and the second at the kidney – The active form of vit D3 (1,25-dihydroxycholecalciferol) regulates the Ca uptake in the intestine and Ca levels in the kidney – Deficiency of Vit D3  defective bone formation and Rickets disease 4 2  12/31/2024 PUBLIC / CYHOEDDUS Vitamin D activation 5 PUBLIC / CYHOEDDUS Vitamin A (Retinol) The retinoids, a family of molecules that are related to retinol (vitamin A), are essential for vision, reproduction, growth, and maintenance of epithelial tissues. Retinoic acid, derived from oxidation of dietary retinol, mediates most of the actions of the retinoids, except for vision, which depends on retinal, the aldehyde derivative of retinol. 6 3  12/31/2024 PUBLIC / CYHOEDDUS Dietary deficiency: Vitamin A, administered as retinol or retinyl esters, is used to treat patients who are deficient in the vitamin. Night blindness is one of the earliest signs of vitamin A deficiency. The visual threshold is increased, making it difficult to see in dim light. Prolonged deficiency leads to an irreversible loss in the number of visual cells. The condition is most frequently seen in children in developing tropical countries. Over 500,000 children worldwide are blinded each year by xerophthalmia caused by insufficient vitamin A in the diet. Acne and psoriasis: Dermatologic problems such as acne and psoriasis are effectively treated with retinoic acid or its derivatives. 7 Vitamin E PUBLIC / CYHOEDDUS Vitamin E is a group of compounds of similar structure; the most active is α-tocopherol Associates with cell membranes, lipids, lipoproteins in the blood An antioxidant; traps HOO and ROO radicals formed as a result of oxidation by O2 of unsaturated hydrocarbon chains in membrane phospholipids  protect the unsaturated F.A from oxidation and prevent oxidative damage to membrane lipid Deficiency of Vit. E : Rough skin, muscular weakness and sterility 8 4  12/31/2024 PUBLIC / CYHOEDDUS Vitamin K Blood clot factor: undergo a cycle of oxidation reduction during the formation of the active prothrombine Functions in blood clotting Deficiency of vitamin K: A true vitamin K deficiency is unusual because adequate amounts are generally produced by intestinal bacteria or obtained from the diet. If the bacterial population in the gut is decreased, for example, by antibiotics, the amount of endogenously formed vitamin is depressed, and this can lead to hypoprothrombinemia in the marginally malnourished individual, Vit K1 (Phylloquinone) 9 PUBLIC / CYHOEDDUS II. water soluble vitamin many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. 10 5  12/31/2024 PUBLIC / CYHOEDDUS II. Folic Acid Folic acid (or folate), which plays a key role in one-carbon metabolism, is essential for the biosynthesis of several compounds. Folic acid deficiency is probably the most common vitamin deficiency in the United States, particularly among pregnant women and alcoholics. A. Function of folic acid Tetrahydrofolate receives one-carbon fragments from donors such as serine, glycine, and histidine and transfers them to intermediates in the synthesis of amino acids, purines, and thymidine monophosphate (TMP)— a pyrimidine found in DNA. 11 PUBLIC / CYHOEDDUS B. Nutritional anemias Anemia is a condition in which the blood has a lower-than-normal concentration of hemoglobin, which results in a reduced ability to transport oxygen. Nutritional anemias—those caused by inadequate intake of one or more essential nutrients—can be classified according to the size of the red blood cells or mean corpuscular volume (MCV) observed in the individual (Figure 28.2). 12 6  12/31/2024 PUBLIC / CYHOEDDUS Microcytic anemia, caused by lack of iron, is the most common form of nutritional anemia. The second major category of nutritional anemia, macrocytic, results from a deficiency in folic acid or vitamin B12. [Note: These macrocytic anemias are commonly called megaloblastic because a deficiency of folic acid or vitamin B12 causes accumulation of large, immature red cell precursors, known as megaloblasts, in the bone marrow and the blood.] Classification of nutritional anemias by cell size. The normal mean corpuscular volume (MCV) for people older than age 18 is between 80 and 100 μm³. [Note: Microcytic anemia is also seen with lead poisoning.] 13 Folate and anemia: Inadequate serum levels of folate can be caused PUBLIC / CYHOEDDUS by increased demand (for example, pregnancy and lactation), P.375 poor absorption caused by pathology of the small intestine, alcoholism, or treatment with drugs that are dihydrofolate reductase inhibitors, for example, methotrexate Figure 28.4 Bone marrow histology in normal and folate-deficient individuals 14 7  12/31/2024 PUBLIC / CYHOEDDUS 15 C. Folate and neural tube defects in the fetus: PUBLIC / CYHOEDDUS Spina bifida and anencephaly, the most common neural tube defects, affect approximately 4,000 pregnancies in the United State annually. Folic acid supplementation before conception and during the first trimester has been shown to significantly reduce the defects. Therefore, all women of childbearing age are advised to consume 0.4 mg/day of folic acid to reduce the risk of having a pregnancy affected by neural tube defects. Adequate folate nutrition must occur at the time of conception because critical folate-dependent development occurs in the first weeks of fetal life—at a time when many women are not yet aware of their pregnancy. 16 8  12/31/2024 PUBLIC / CYHOEDDUS The U.S. Food and Drug Administration has authorized the addition of folic acid to enriched grain products, resulting in a dietary supplementation of about 0.1 mg/day. It is estimated that this supplementation will allow approximately fifty percent of all reproductive-aged women to receive 0.4 mg of folate from all sources. However, folic acid intake should not exceed approximately 1 mg/day to avoid complicating the diagnosis of vitamin B12 deficiency. 17 III. Cobalamin (Vitamin B12) PUBLIC / CYHOEDDUS Vitamin B12 is required in humans for two essential enzymatic reactions: the remethylation of homocysteine to methionine and the isomerization of methylmalonyl coenzyme A (CoA) that is produced during the degradation of some amino acids, and fatty acids with odd numbers of carbon atoms. When the vitamin is deficient, abnormal fatty acids accumulate and become incorporated into cell membranes, including those of the nervous system. This may account for some of the neurologic manifestations of vitamin B12 deficiency. 18 9  12/31/2024 PUBLIC / CYHOEDDUS A. Structure of cobalamin and its coenzyme forms Cobalamin contains a corrin ring system that differs from the porphyrins in that two of the pyrrole rings are linked directly rather than through a methene bridge. Cobalt is held in the center of the corrin ring by four coordination bonds from the nitrogens of the pyrrole groups. Structure of vitamin B12 (cyanocobalamin) and its coenzyme forms (methylcobalamin and 5′- deoxyadenosyl-cobalamin). 19 B. Distribution of cobalamin PUBLIC / CYHOEDDUS Vitamin B12 is synthesized only by microorganisms; it is not present in plants. Animals obtain the vitamin preformed from their natural bacterial flora or by eating foods derived from other animals. Cobalamin is present in appreciable amounts in liver, whole milk, eggs, oysters, fresh shrimp, pork, and chicken. Absorption of vitamin B12 IF = intrinsic factor (Glycoprotein) 20 10  12/31/2024 D. Clinical indications for vitamin B12 PUBLIC / CYHOEDDUS In contrast to other water-soluble vitamins, significant amounts (4–5 mg) of vitamin B12 are stored in the body. As a result, it may take several years for the clinical symptoms of B12 deficiency to develop in individuals who have had a partial or total gastrectomy. 1-Pernicious anemia: Vitamin B12 deficiency is rarely a result of an absence of the vitamin in the diet. Patients with cobalamin deficiency are usually anemic, but later in the development of the disease they show neuropsychiatric symptoms. However, central nervous system (CNS) symptoms may occur in the absence of anemia. The CNS effects are irreversible and occur by mechanisms that appear to be different from those described for megaloblastic anemia. The disease is treated by giving high-dose B12 orally, or intramuscular injection of cyanocobalamin. Therapy must be continued throughout the lives of patients with pernicious anemia. 21 V. Pyridoxine (Vitamin B6) PUBLIC / CYHOEDDUS Vitamin B6 is a collective term for pyridoxine, pyridoxal, and pyridoxamine, all derivatives of pyridine. They differ only in the nature of the functional group attached to the ring (Figure 28.10). Pyridoxine occurs primarily in plants, whereas pyridoxal and pyridoxamine are found in foods obtained from animals. All three compounds can serve as precursors of the biologically active coenzyme, pyridoxal phosphate. Pyridoxal phosphate functions as a coenzyme for a large number of enzymes, particularly those that catalyze reactions involving amino acids. 22 11  12/31/2024 PUBLIC / CYHOEDDUS A. Clinical indications for pyridoxine: Isoniazid (isonicotinic acid hydrazide), a drug frequently used to treat tuberculosis, can induce a vitamin B6 deficiency by forming an inactive derivative with pyridoxal phosphate. Dietary supplementation with B6 is, thus, an adjunct to isoniazid treatment. Otherwise, dietary deficiencies in pyridoxine are rare but have been observed in newborn infants fed formulas low in B6, in women taking oral contraceptives, and in alcoholics. B. Toxicity of pyridoxine Neurologic symptoms have been observed at intakes of greater than 2g/day. Substantial improvement, but not complete recovery, occurs when the vitamin is discontinued. 23 VI. Thiamine (Vitamin B1) PUBLIC / CYHOEDDUS Thiamine pyrophosphate is the biologically active form of the vitamin, formed by the transfer of a pyrophosphate group from adenosine triphosphate (ATP) to thiamine (Figure 28.11). Thiamine pyrophosphate serves as a coenzyme in the formation or degradation of α-ketols by transketolase (Figure 28.12A), and in the oxidative decarboxylation of α-keto acids. A. Clinical indications for thiamine The oxidative decarboxylation of pyruvate and α-ketoglutarate, which plays a key role in energy metabolism of most cells, is particularly important in tissues of the nervous system. In thiamine deficiency, the activity of these two dehydrogenase reactions is decreased, resulting in a decreased production of ATP. 1. Beriberi: This is a severe thiamine-deficiency syndrome found in areas where polished rice is the major component of the diet. Signs of infantile beriberi include tachycardia, vomiting, convulsions, and, if not treated, death. 24 12  12/31/2024 Wernicke-Korsakoff syndrome: In the United States, thiamine deficiency, PUBLIC / CYHOEDDUS which is seen primarily in association with chronic alcoholism, is due to dietary insufficiency or impaired intestinal absorption of the vitamin. Thiamine deficiency state characterized by apathy, loss of memory, ataxia, and a rhythmic to-and-fro motion of the eyeballs (nystagmus). 25 VII. Niacin PUBLIC / CYHOEDDUS Niacin, or nicotinic acid, is a substituted pyridine derivative. The biologically active coenzyme forms are nicotinamide adenine dinucleotide (NAD+) and its phosphorylated derivative, nicotinamide adenine dinucleotide phosphate (NADP+). Nicotinamide, a derivative of nicotinic acid that contains an amide instead of a carboxyl group, also occurs in the diet. 26 13  12/31/2024 PUBLIC / CYHOEDDUS NAD+ and NADP+ serve as coenzymes in oxidation-reduction reactions in which the coenzyme undergoes reduction of the pyridine ring by accepting a hydride ion (hydrogen atom plus one electron, Figure 28.14). The reduced forms of NAD+ and NADP+ are NADH and NADPH, respectively. 27 PUBLIC / CYHOEDDUS A. Distribution of niacin Niacin is found in unrefined and enriched grains and cereal, milk, and lean meats, especially liver. B. Clinical indications for niacin Deficiency of niacin: A deficiency of niacin causes pellagra, a disease involving the skin, gastrointestinal tract, and CNS. The symptoms of pellagra progress through the three Ds: dermatitis, diarrhea, dementia—and, if untreated, death. Often referred to as coenzyme 1, NADH is the body’s top-ranked coenzyme, a facilitator of numerous biological reactions. NADH is necessary for cellular development and energy production: It is essential to produce energy from food and is the principal carrier of electrons in the energy-producing process in the cells. 28 14  12/31/2024 PUBLIC / CYHOEDDUS Treatment of hyperlipidemia: Niacin (at doses of 1.5 g/day or 100 times the Recommended Dietary Allowance or RDA) strongly inhibits lipolysis in adipose tissue—the primary producer of circulating free fatty acids. The liver normally uses these circulating fatty acids as a major precursor for triacylglycerol synthesis. Thus, niacin causes a decrease in liver triacylglycerol synthesis, which is required for very-low-density lipoprotein (VLDL, see p. 231) production. Low-density lipoprotein (LDL, the cholesterol-rich lipoprotein) is derived from VLDL in the plasma. Thus, both plasma triacylglycerol (in VLDL) and cholesterol (in VLDL and LDL) are lowered. Therefore, niacin is particularly useful in the treatment of Type IIb hyperlipoproteinemia, in which both VLDL and LDL are elevated. 29 PUBLIC / CYHOEDDUS VIII. Riboflavin (Vitamin B2) The two biologically active forms are flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), formed by the transfer of an adenosine monophosphate moiety from ATP to FMN (Figure 28.15). FMN and FAD are each capable of reversibly accepting two hydrogen atoms, forming FMNH2 or FADH2. 30 15  12/31/2024 PUBLIC / CYHOEDDUS FMN and FAD are bound tightly—sometimes covalently— to flavoenzymes that catalyze the oxidation or reduction of a substrate. Riboflavin deficiency is not associated with a major human disease, although it frequently accompanies other vitamin deficiencies. Deficiency symptoms include dermatitis, cheilosis (fissuring at the corners of the mouth), and glossitis (the tongue appearing smooth and purplish). 31 IX. Biotin PUBLIC / CYHOEDDUS Biotin is a coenzyme in carboxylation reactions, in which it serves as a carrier of activated carbon dioxide. Biotin is covalently bound to the ε-amino groups of lysine residues of biotin- dependent enzymes (Figure 28.16). Biotin deficiency does not occur naturally because the vitamin is widely distributed in food. Also, a large percentage of the biotin requirement in humans is supplied by intestinal bacteria. the addition of raw egg white to the diet as a source of protein induces symptoms of biotin deficiency, namely, dermatitis, glossitis, loss of appetite, and nausea. 32 16  12/31/2024 PUBLIC / CYHOEDDUS X. Pantothenic Acid Pantothenic acid is a component of CoA, which functions in the transfer of acyl groups (Figure 28.17). Coenzyme A contains a thiol group that carries acyl compounds as activated thiol esters. Examples of such structures are succinyl CoA, fatty acyl CoA, and acetyl CoA. Pantothenic acid is also a component of fatty acid synthase (see p. 184). Eggs, liver, and yeast are the most important sources of pantothenic acid, although the vitamin is widely distributed. Pantothenic acid deficiency is not well characterized in humans, and no Recommended Dietary Allowance (RDA) has been established. 33 PUBLIC / CYHOEDDUS IV. Ascorbic Acid (Vitamin C) The active form of vitamin C is ascorbate acid (Figure 28.8). The main function of ascorbate is as a reducing agent in several different reactions. Vitamin C has a well-documented role as a coenzyme in hydroxylation reactions, for example, hydroxylation of prolyl and lysyl residues of collagen. Vitamin C is, therefore, required for the maintenance of normal connective tissue, as well as for wound healing. Vitamin C also facilitates the absorption of dietary iron from the intestine 34 17  12/31/2024 PUBLIC / CYHOEDDUS A. Deficiency of ascorbic acid A deficiency of ascorbic acid results in scurvy, a disease characterized by sore and spongy gums, loose teeth, fragile blood vessels, swollen joints, and anemia (Figure 28.9). Many of the deficiency symptoms can be explained by a deficiency in the hydroxylation of collagen, resulting in defective connective tissue. B. Prevention of chronic disease Vitamin C is one of a group of nutrients that includes vitamin E, A (see p. 391) and β-carotene (see p. 382), which are known as antioxidants. P.378 Consumption of diets rich in these compounds is associated with a decreased incidence of some chronic diseases, such as coronary heart disease and certain cancers. However, clinical trials involving supplementation with the isolated antioxidants have failed to determine any convincing beneficial effects. 35 PUBLIC / CYHOEDDUS Thank you for your attention I hope you got something of benefit from the lecture Any Questions? Nothing is perfect, So If you find any mistakes let me know 36 18