Lecture 11 - Vitamins II - MSA University PDF

Vitamins II PHB231 Water Soluble Vitamins Week 11 By the end of this lecture, you should be able to: Identify water soluble vitamins. State their functions. Understand associated deficiencies. Enumerate their clinical indication. Classification  Water soluble vitamins...

Vitamins II PHB231 Water Soluble Vitamins Week 11 By the end of this lecture, you should be able to: Identify water soluble vitamins. State their functions. Understand associated deficiencies. Enumerate their clinical indication. Classification  Water soluble vitamins Vitamin C (Ascorbic acid): It is naturally present in some foods, added to others, and as a dietary supplement. Humans, unlike most animals, are unable to synthesize vitamin C endogenously, so it is an essential dietary component. The RDA is 90 mg/day for adult men and 75 mg/day for adult women  A. Functions Reducing agent Coenzyme in Biosynthesis of L- (Antioxidant) hydroxylation carnitine and Regeneration of reactions (Keep some vitamin E Fe2+) neurotransmitters Maintenance of normal connective Facilitates dietary tissue and wound Fe2+ absorption healing (Collagen)  B. Deficiency 1. Scurvy: Sore and spongy gums. Loose teeth. Fragile blood vessels. Poor wound healing. Frequent infections. These symptoms are due to decreased hydroxylation of collagen resulting in defective connective tissue. 2. Microcytic anemia.  Vitamin B complex Vitamin Coenzyme Vit B1 (Thiamine) TPP Vit B2 (Riboflavin) FAD, FMN Vit B3 (Niacin) NAD, NADP Vit B5 (Pantothenic acid) CoASH Vit B6 (Pyridoxamine) Pyridoxal Phosphate (PLP) Biotin (Vit H/Vit B7) Biotin Folate (Vit B9) THF B12 (Cobolamine) Cobolamine  Water soluble vitamins Folic acid (Vitamin B9) Sources: Leafy and dark green vegetables. It plays a key role in one-carbon metabolism (methyl, methylene, methenyl, formyl, or formimino) which is bound to positions N5, N10, or both. It is essential for the biosynthesis of several compounds as DNA, polyamines, amino acids, creatine, and phospholipids. Its deficiency is probably the most common vitamin deficiency in the United States, particularly among pregnant women and individuals with alcoholism. A. Function  A. Function Tetra hydro folate (reduced folate): 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 mono phosphate (TMP).  B. Deficiency Nutritional anemias: Caused by inadequate intake of one or more essential nutrients. Blood has a lower-than-normal concentration of hemoglobin, which results in a reduced ability to transport oxygen.  B. Deficiency 1. Folate and anemia: Deficiency of folate is due to: Increased demand (pregnancy and lactation). Poor absorption (pathology or alcoholism). DHF reductase inhibitors (as Methotrexate). Megaloblastic anemia: caused by diminished synthesis of purines and TMP, which leads to an inability of cells (including red cell precursors) to make DNA and, therefore, they cannot divide.  B. Deficiency 2. Neural tube defects in the fetus: Folic acid supplementation before conception and during the first trimester has been shown to significantly reduce the defects of spina bifida and anencephaly in fetus. An RDA of 0.4 mg/day reduce the risk. However, there is an association of high-dose supplementation with folic acid (>0.8 mg/day) and an increased risk of cancer. Thus, supplementation is not  Water soluble vitamins Vitamin B12 (Cobalamin) The RDA is 2.4 μg/day. Synthesized only by microorganisms and not present in plants. Sources: food from animal origin (Liver, red meat, eggs, dairy products or fortified cereals).  A. Function The re-methylation of homocysteine (Hcy) to methionine. N5-methyl THF is also required in the re-methylation of Hcy. Therefore, deficiency of B12 or folate results in elevated Hcy levels.  B. Deficiency Pronounced in rapidly dividing cells, such as the erythropoietic tissue of bone marrow and the mucosal cells of the intestine. These tissues need both the N5, N10-methylene and N10-formyl forms of THF for the synthesis of nucleotides required for DNA replication. Folate is trapped in the N5-methyl form, which accumulates due to impairment of Hcy to methionine conversion, and the level of other forms decreases. Such folate-vitamin B12 dependent deficiency causes megaloblastic anemia.  Thiamine (Vitamin B1) Thiamine pyrophosphate (TPP) is the biologically active form of the vitamin B1. It is activated by the transfer of a pyrophosphate group from adenosine triphosphate (ATP). It serves as a coenzyme in the oxidative decarboxylation of α-keto acids (Very important reaction e.g: Krebs’ cycle).  Thiamine (Vitamin B1) Oxidative decarboxylation of pyruvate and α- ketoglutarate plays a key role in energy metabolism of most cells, particularly important in tissues of the nervous system. Thiamine deficiency, result in a decreased production of ATP and, thus, impaired cellular function.  Thiamine (Vitamin B1) Recommended Dietary Allowance (RDA): Males 1.2 mg/day Females 1.1 mg/day Function: TPP (thiamine pyrophosphate) is essential for energy metabolism (carbohydrates) especially in the CNS. Sources: Whole grain. Moderate amounts in ALL nutrients.  Riboflavin (Vitamin B2) The two biologically active forms are flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). FMN and FAD are bound tightly sometimes covalently to flavoenzymes that catalyze the oxidation or reduction of a substrate. Riboflavin is important in energy production in the body.  Riboflavin (Vitamin B2) RDA: Males 1.3 mg/day. Females 1.1 mg/day. Stable to heat but Riboflavin is water soluble so usually lost during food processing. Deficiency: Deficiency is not common but usually combined with other vitamins deficiency. Ariboflavinosis characterized by inflammation of the membranes of the mouth, skin, eyes, and GI tract.  Niacin (Vitamin B3) Known also as nicotinic acid. Nicotinamide present in diet can be converted to nicotinic acid in body. Dietary tryptophan is a precursor. 1% of protein weight is Tryptophan (60 mg Tryptophan ≅ 1mg niacin).  Niacin (Vitamin B3) RDA: Males 16 mg NE/day. Females 14 mg NE/day. Forms: NAD (Nicotinamide adenine dinucleotide) and NADP coenzymes. Very important for metabolic reactions (Krebs’ cycle). Sources: Poultry, fish, liver and whole grains.  Niacin (Vitamin B3) Deficiency: Pellagra: Diarrhea. Dermatitis. Dementia. Death (the four Ds).  Niacin (Vitamin B3) Primary pellagra occurs due to malnutrition when a person is not getting enough niacin or tryptophan in the diet. It is commonly noticed in developing countries that depend on corn as a staple food. secondary pellagra is when the body is unable to process the niacin properly due to gastrointestinal issues that inhibit the body from absorbing niacin. Clinical importance: 1.5 g/day dose can help in the treatment of hyperlipidemia. Decreases lipolysis so decreases VLDL and LDL in plasms.  Pantothenic acid (Vitamin B5) Adequate intake: Adults: 5 mg/day. Function: CoA is essential for energy metabolism. CoA contains a thiol group that carries acyl compounds as activated thiol esters. Formation of acetyl CoA (for Krebs’ cycle, fatty acid formation, cholesterol synthesis, ketone body synthesis). Sources: Moderate amounts in ALL nutrients (Destroyed by food processing (freezing, canning and processing). Deficiency: Rare but results in vomiting, hypoglycemia, cramps.  Pyridoxal (Vitamin B6) Vitamin B6 is a collective term for pyridoxine, pyridoxal, and pyridoxamine. 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 (PLP). Pyridoxal phosphate functions as a coenzyme for a large number of enzymes, particularly those that catalyze reactions involving amino acids: Transamination, Deamination, decarboxylation and condensation. Histidine → histamine + CO2 (decarboxylation of histidine)  Pyridoxal (Vitamin B6) RDA: Adults: 1.3mg/day. Clinical indications 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. Toxicity: Pyridoxine is the only water-soluble vitamin with significant toxicity. Neurotoxicity (Depression, fatigue, irritability, headaches, nerve damage causing numbness and muscle weakness).  Biotin (Vitamin B7/Vitamin H) RDA: Adults: 30 μg/day. Function: Coenzyme for decarboxylase enzyme essential in TCA (Kreb’s cycle) and gluconeogenesis. Sources: Moderate amounts in ALL nutrients Produced by gut normal flora Deficiency: Rare but results in depression, lethargy, hallucinations and hair loss.