Lecture 89 Vitamins 2024 PDF

Vitamins Dr. Sarray Sameh, Ph.D Vitamin Facts Vitamins are essential organic nutrients, Required in small amounts. They cannot be synthesized in adequate amount by the body (must be obtained by outside sources like diet, rumen bacteria & sun). Required for growth, maintenance, reproduction and lacta...

Vitamins Dr. Sarray Sameh, Ph.D Vitamin Facts Vitamins are essential organic nutrients, Required in small amounts. They cannot be synthesized in adequate amount by the body (must be obtained by outside sources like diet, rumen bacteria & sun). Required for growth, maintenance, reproduction and lactation…. not stored in tissues, must have constant supply stored in tissues (liver and adipose tissue) e Fat Soluble Vitamins Vitamin A Vitamin A is often used as a collective term for several related biologically active molecules. The term retinoids includes both natural and synthetic forms of vitamin A; Structure: 4 forms of vitamin A Retinol: found in animal tissues; primary alcohol containing a β-ionone ring with an unsaturated side chain; Retinal: aldehyde derived from the oxidation of retinol. Retinol and retinal can be interconverted Retinoic acid: Acid derived from the oxidation of retinal. Cannot be reduced in the body, and, therefore, cannot give rise to either retinal or retinol -Carotene: found in plant foods, which can be oxidatively cleaved in the intestine to yield two molecules of retinal. Vitamin A (Cont.) Sources: liver, kidney, butter and egg yolk Sources of carotenes: yellow and dark green vegetables and fruits Functions: Development healthy skin and nerve tissue. maintaining healthy vision epithelial Tissue differenciation Reproduction, supporting spermatogenesis in male Deficiency signs: Retarded growth in the young Xerophthalmia: dryness of conjunctiva and cornea night blindness and reproductive disorders. Hypervitaminosis A (Excessive intake of vitamin A): clinical signs: the skin becomes dry and pruritic; the liver enlarge and can become cirrhotic... Vitamin E Called tocopherol About 8 tocopherols have been identified. There are 4 main forms of tocopherols: and  tocopherols;  tocopherol is most active and predominant form of vitamin E Functions: Antioxidant: prevention from cell damage caused by free radicals such as H2O2 (hydrogen peroxide). Reproductive function and prevents sterility Prevents RBC from hemolysis by oxidizing agents (H2O2) Sources: cereal grains vegetable oils ( peanut oil, corn oil and sunflower oil), meat, eggs and milk Recommended dietary allowance (RDA) : 10mg (15IU) of -tocopherol for man and 8mg (12IU) for women is recommended. (1mg of -tocopherol is equal to 1.5IU) Deficiency symptoms: is almost entirely restricted to premature infants; When observed in adults, it is associated with a defective lipid absorption or transport , sterility, degenerative changes in muscle Toxicity of vitamin E: Vitamin E is the least toxic of the fat-soluble vitamins, and no toxicity has been observed even at doses of 300 mg/day Vitamin D Vitamin D is a fat soluble steroid essential for maintaining calcium metabolism. Active molecule: is calcitriol (1,25-dihydroxycholecalciferol)  Sources: Exogenous precursors of vit D: Ergocalciferol (vitamin D2) found in plants, and cholecalciferol (vitamin D3) found in animal tissues Endogenous vitamin precursor:7-dehydrocholesterol, an intermediate in cholesterol synthesis, is converted to cholecalciferol in the dermis and epidermis of humans exposed to sun light. Functions of vitamin D o Maintain adequate plasma levels of calcium (calcium homeostasis) by: - increasing uptake of calcium by the intestine, - minimizing loss of calcium by the kidney, - stimulating resorption of bone when necessary (In vitamin D deficiency, calcium absorption is insufficient and cannot satisfy the body’s needs. Consequently, parathyroid hormone (PTH) production increases and calcium is mobilized from bones and reabsorbed in the kidneys to maintain normal serum calcium levels). Distribution and requirements of vitamin D Vitamin D occurs naturally in fatty fish, liver, and egg yolk. RDA for individuals ages 1-70 years is 15 µg/day and over age 70 years20 µg/day. Deficiency: Demineralization of bone: resulting in rickets in children and osteomalacia in adults. Toxicity of vitamin D: High doses (100,000 IU for weeks or months) can cause loss of appetite, nausea, thirst, and weakness. Enhanced calcium absorption and bone resorption results in hyper-calcemia, which can lead to deposition of calcium in many organs (calcification), particularly the arteries and kidneys. Metabolism of vitamin D Once the skin is exposed to UV radiation from the light, 7dehydrocholesterol is converted into cholecalciferol, then two sequential hydroxylation reactions occur: - In the liver: The first hydroxylation is catalyzed by 25-hydroxylase enzyme leading to 25-hydroxycholecalciferol (25-OH-D3) or calcidiol; is the predominant form of vitamin D in the plasma and the major storage form of the vitamin. - In the kidney, The calcidiol is further hydroxylated by 25- hydroxycholecalciferol 1-hydroxylase resulting in the formation of 1,25-dihydroxycholecalciferol (1,25-diOH-D3) or calcitriol. Vitamin K o There are 2 naturally occurring forms of vitamin K: o vitamin K1 (phylloquinone) derived from plants, o vitamin K2 (menaquinone) produced by intestinal bacterial flora. o Functions: It is necessary for blood clotting and bone health Post-translational modification of a number of clotting factors Vitamin K is called an anti-hemorragic factor as its deficiency leads to uncontrolled hemorrhages due to a defect in coagulation system. Vitamin K Source: Widely distributed in nature (cabbage, spinach, egg yolk, and liver); it is also produced by the intestinal microflora ensures that dietary deficiency does not occur. Vitamin K deficiency occurs: in the newborn: Newborns have sterile intestines after birth and lack the bacteria that synthesize vitamin K. It is recommended that all newborns receive a single intramuscular dose of vitamin K as prophylaxis against hemorrhagic disease. If the bacterial population in the gut is decreased and the amount vitamin is decreased, leading to hypo-prothrombinemia; This condition may require supplementation with vitamin K to correct the bleeding tendency. Toxicity of vitamin K: Prolonged administration of large doses of synthetic vitamin K can produce hemolytic anemia and jaundice in the infant, due to increased break down of RBCs. Water Soluble Vitamins Vitamin C Active form: ascorbic acid Functions: - It is a reducing agent in different reactions. - Essential for the production of collagen and the wound healing. - Facilitates the absorption of dietary iron. - Antioxidant, and consumption of diet rich in it is associated with a decreased incidence of chronic diseases like coronary heart diseases and certain cancers. Deficiency in vitamin C: Scurvy o Typical symptoms are: sore and spongy gums, loose teeth, Easy bruising, swollen joints and anemia. Vitamin B1 (Thiamin) oThiamine pyrophosphate (TPP) is the biologically active form of vitamin B1, formed by transfer of a pyrophosphate group from ATP to thiamine. oFunction: TPP serves as a coenzyme in the oxidative decarboxylation of α-keto acids. oIn thiamine deficiency: the oxidative decarboxylation of pyruvate and α-ketoglutarate is decreased resulting in decreased production of ATP and impaired cellular functions oClinical deficiency signs: loss of appetite, muscular weakness, severe nervous disorders and BeriBeri. oBeriberi: is a severe thiamine-deficiency syndrome found in areas where polished rice is the major component of the diet. oInfantile beriberi is seen in nursing infants whose mothers are deficient in thiamine. oAdult Beriberi: dry (characterized by peripheral neurologic deficits) or wet (characterized by edema due to cardiac dysfunction). o Both beriberi are treatable with thiamine supplementation. Vitamin B2 (Riboflavin) o Two biologically active forms of riboflavin are: o flavin mononucleotide (FMN) and o flavin adenine dinucleotide (FAD). o FMN and FAD are capable of reversibly accepting two hydrogen atoms, forming FMNH2 or FADH2. o Functions: normal embryo development, metabolism reactions of amino acids and carbohydrates. o Riboflavin deficiency symptoms: o Dermatitis, cheilosis (fissuring at the corners of the mouth), and glossitis (the tongue appearing smooth and dark). Vitamin B3 (Niacin-Nicotinic acid) The biologically active forms: nicotinamide adenine dinucleotide (NAD+) and phosphorylated derivative nicotinamide adenine dinucleotide phosphate (NADP+). Functions: coenzymes in oxidation-reduction reactions inhibits lipolysis in adipose tissue; this lipolysis is considered as the primary producer of circulating free fatty acids and normally, the liver uses these circulating fatty acids as a major precursor for triacylglycerol synthesis. Thus, niacin causes a decrease in liver triacylglycerol synthesis. Niacin deficiency: Pellagra is a three Ds disease: dermatitis, diarrhea, dementia, and if untreated, death. Vitamin B9 (Folic acid/Folate) Folic acid is the oxidized form of the vitamin; The reduced form, tetrahydrofolate (THF), is the active form of folic acid Folate/folic acid is enzymatically reduced in 2 stage process in tissues to yield dihydrofolic acid and tetrahydrofolic acid. THF act as carrier of one carbon fragments: it accepts one carbon from degradation reactions and donates in reactions involved in amino acid and nucleotide metabolism Folic acid deficiency Deficiency may result from: -Insufficient dietary intake -Poor intestinal absorption -Excessive demands as in pregnancy , liver disease and malignancies -Administration of anti-folate drugs like methotrexate and anticonvulsant therapy Clinical manifestations -Macrocytic anemia/ megaloblastic anemia (deficiency of folic acid or vit B12), causes accumulation of immature and large red cell precursors known as megaloblasts in the bone marrow and blood; this inability to divide is due to a reduction in the synthesis of purines and TMP, which leads to an inability of cells to make DNA (cannot divide). -Sensory loss -Neuropsychiatric changes -Neural tube defects in the fetus during pregnancy, resulting in Spina bifida and anencephaly. Folic acid supplementation before conception and during the first trimester reduces the risk!!! Spina bifida anencephaly Cobalamin (Vitamin B12) Involved in the production of red blood cells and DNA synthesis Active forms of vit B12: methylcobalamin and deoxyadenosylcobalamin Required in humans for two essential enzymatic reactions: Remethylation of homocysteine to methionine Isomerization of methylmalonyl coenzyme A (CoA) that is produced during the degradation of branched chain amino acids and also from fatty acids with odd numbers of carbon atoms. Clinical indications for vitamin B12: In contrast to other water-soluble vitamins, Significant amounts (2–5mg) of vitamin B12 are stored in the body. As result, It may take several years for the clinical symptoms of B12 deficiency to develop. Vitamin B12 deficiency: rarely but can result from: - Absence of the vitamin B12 in the diet - Malabsorption - Pernicious anemia caused by a deficiency of intrinsic factor which leads to impaired absorption of cobalamin The clinical manifestation of vit B12: - Megaloblastic anemia - Neuropathy and irreversible neurologic disorders - Methylmalonic aciduria Deficiency of vitamin B12 can be measured by the level of methylmalonic acid in blood, which will be high The treatment is by taken a high dose of B12 orally or by intramuscular injection. Pyridoxine /vitamin B6 Vitamin B6 is a collective term for Pyridoxine, pyridoxal and pyridoxamine, all are derivatives of pyridine. They differ only in the nature of the functional group attached to the ring. Distribution: Pyridoxine in plants; pyridoxal and pyridoxamine are found in foods obtained from animals. All three compounds can serve as precursors of the biologically active coenzyme, pyridoxal phosphate (PLP) which is a coenzyme for a large number of enzymes particularly that catalyze reaction with aminoacids (transamination, …) Pyridoxine (vitamin B6) Deficiency: in newborn infants fed formulas low in B6; in women taking oral contraceptives and in alcoholic persons. Clinical indications for pyridoxine: Isoniazid a drug used for treatment of tuberculosis can induce a vitamin B6 deficiency by forming an inactive derivative with pyridoxal phosphate thus dietary supplementation with B6 is an adjunct to isonazid treatment. Toxicity of pyridoxine: It is the only water-soluble vitamin with significant toxicity. Neurologic symptoms occurs at intakes above 200 mg/day, an amount 100 times the RDA. Biotin (vitamin B7) Biotin is a coenzyme in carboxylation reactions Biotin is covalently bound to the amino groups of lysine residues in biotin-dependent enzymes. Biotin deficiency does not occur naturally because the vitamin is widely distributed in food. Large percentage is supplied by intestinal bacteria. Addition of raw egg white to the diet as a source of protein induces symptoms of biotin deficiency namely, dermatitis, hair loss, loss of appetite and nausea. Raw egg white contains a glycoprotein avidin, which tightly binds biotin and prevents its absorption. Pantothenic acid (vitamin B5) It is a component of coenzyme A (CoA) which functions in the transfer of acyl groups. Pantothenic acid is also a component of the acyl carrier protein (ACP) domain of fatty acid synthase (important enzyme in fatty acid synthesis) Eggs, liver, and yeast are the most important sources.