Water Soluble Vitamins Chapter 12 PDF

Water Soluble Vitamins 1  Objectives Explain the metabolic roles of water-soluble vitamins. Identify water-soluble vitamin deficiency states. Recall the metabolic functions of vitamins and clinical signs of deficiency....

Water Soluble Vitamins 1  Objectives Explain the metabolic roles of water-soluble vitamins. Identify water-soluble vitamin deficiency states. Recall the metabolic functions of vitamins and clinical signs of deficiency. 2  Introduction Vitamins are chemically unrelated organic compounds that cannot be synthesized in adequate quantities by humans and, therefore, must be supplied by the diet. A vitamin is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. The vitamins that are classified as water-soluble are readily excreted in the urine, so toxicity is rare. Four vitamins (A, D, K, and E) are termed fat-soluble vitamins. 3 4  Water soluble vitamins 1. Folic acid-Vitamin B9 2. Cobalamin-Vitamin B12 3. Vitamin C 4. Pyridoxine-Vitamin B6 5. Thiamine-Vitamin B1 6. Niacin-Vitamin B3 7. Riboflavin-Vitamin B2 8. Biotin-Vitamin B7 9. Pantothenic acid-Vitamin B5 5  Water soluble vitamins 1. Folic acid-Vitamin B9 2. Cobalamin-Vitamin B12 3. Vitamin C 4. Pyridoxine-Vitamin B6 5. Thiamine-Vitamin B1 6. Niacin-Vitamin B3 7. Riboflavin-Vitamin B2 8. Biotin-Vitamin B7 9. Pantothenic acid-Vitamin B5 6 7  Folic acid (vitamin B9) Folic acid (or folate) plays a key role in one-carbon metabolism. Folic acid deficiency is probably the most common vitamin deficiency, particularly among pregnant women and alcoholics. The function of folic acid : – Tetrahydrofolate (THF), the reduced, coenzyme form of 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 monophosphate (TMP), a pyrimidine nucleotide found in DNA. 8 Function of folic acid 9  Dihydrofolate reductase (DHFR) inhibitors Folate is needed by rapidly dividing cells to make thymine. Molecules that inhibit the function of dihydrofolate reductase ➔ antifolate drugs➔ this effect may be used to therapeutic advantage. Methotrexate is used in cancer chemotherapy because it can prevent neoplastic cells from dividing. Bacteria also need DHFR to grow and multiply and hence inhibitors selective for bacterial NOT for host DHFR have found application as antibacterial agents (e.g: trimethoprim dug). 10 Folate Deficiency Folate and anemia: inadequate serum levels of folate can be caused by: – Increased demand (for example, pregnancy and lactation) – Poor nutrition – Poor absorption caused by pathology of the small intestine, alcoholism – Treatment with drugs (for example, methotrexate) that are dihydrofolate reductase inhibitors. A primary result of folic acid deficiency is megaloblastic anemia. Folate and neural tube defects in the fetus (Spina bifida) 11 12  Water soluble vitamins 1. Folic acid-Vitamin B9 2. Cobalamin-Vitamin B12 3. Vitamin C 4. Pyridoxine-Vitamin B6 5. Thiamine-Vitamin B1 6. Niacin-Vitamin B3 7. Riboflavin-Vitamin B2 8. Biotin-Vitamin B7 9. Pantothenic acid-Vitamin B5 13  Cobalamin (vitamin B12) Vitamin B12 is required in humans for two essential enzymatic reactions: 1. The remethylation of homocysteine (Hcy) to methionine. 2. The isomerization of methylmalonyl coenzyme A (CoA), which is produced during the degradation of some amino acids (isoleucine, valine, threonine, and methionine) and fatty acids (FAs) with odd numbers of carbon atoms. 14 15 Cobalamin (vitamin B12) 16  Distribution of cobalamin Vitamin B12 is synthesized only by microorganisms, and 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, red meat, fish, eggs, dairy products, and fortified cereals. 17  Vitamin B12 absorption Absorption depends on – adequate dietary intake. – Acid pepsin in the stomach: B12 is released from food in the acidic environment of the stomach. – Pancreatic lipases. – Gastric secretion of functional intrinsic factors (IF). – Ileum with functioning B12-IF receptors. Vitamin B12 deficiency is most commonly seen in patients who fail to absorb the vitamin from the intestine. 18  Clinical indications for vitamin B12 In contrast to other water-soluble vitamins, significant amounts (2–5 mg) of vitamin B12 are stored in the body, the daily needs is about 2.5ug. As a result, it may take several years for the clinical symptoms of B12 deficiency to develop as a result of decreased intake of the vitamin. Vitamin B12 deficiency anemia, the produced red blood cells are reduced due to a deficiency of vitamin B12 ➔ Macrocytec anemia Pernicious anemia (PA): destruction and decreased level of IF ➔ low Vit B12 19  Water soluble vitamins 1. Folic acid-Vitamin B9 2. Cobalamin-Vitamin B12 3. Vitamin C 4. Pyridoxine-Vitamin B6 5. Thiamine-Vitamin B1 6. Niacin-Vitamin B3 7. Riboflavin-Vitamin B2 8. Biotin-Vitamin B7 9. Pantothenic acid-Vitamin B5 20  Ascorbic acid (vitamin C) The active form of vitamin C is ascorbic acid. 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. Vitamin C also reduces ferric iron to the ferrous form, thereby facilitating the absorption of dietary iron from the intestine. 21  Deficiency of ascorbic acid Deficiency of ascorbic acid results in scurvy, a disease characterized by sore and spongy gums, loose teeth, fragile blood vessels, swollen joints, fatigue, Microcytic anemia is caused by decreased absorption of iron. Many of the deficiency symptoms can be explained by a deficiency in the hydroxylation of collagen, resulting in defective connective tissue. 22 23  Water soluble vitamins 1. Folic acid-Vitamin B9 2. Cobalamin-Vitamin B12 3. Vitamin C 4. Pyridoxine-Vitamin B6 5. Thiamine-Vitamin B1 6. Niacin-Vitamin B3 7. Riboflavin-Vitamin B2 8. Biotin-Vitamin B7 9. Pantothenic acid-Vitamin B5 24  Pyrodoxine (vitamin B6) Vitamin B6 is a collective term for pyridoxine, pyridoxal, pyridoxal phosphate (PLP) and pyridoxamine, all derivatives of pyridine. Biologically active coenzyme, pyridoxal phosphate (PLP). They differ only in the nature of the functional group attached to the ring. Pyridoxine (in plants), whereas pyridoxal and pyridoxamine (from animals). 25 26  Vitamin B6 Pyridoxine, pyridoxal, and pyridoxamine can serve as precursors of the biologically active coenzyme, pyridoxal phosphate (PLP). PLP functions as a coenzyme for a large number of enzymes, particularly those that catalyze reactions involving amino acids, for example, transamination, deamination, decarboxylation, and condensation. 27 28  Clinical indications for vitamin B6 Isoniazid, a drug commonly used to treat tuberculosis, can induce a vitamin B6 deficiency by forming an inactive derivative with PLP. Dietary supplementation with B6 is, thus, an adjunct to isoniazid treatment. 29  Toxicity of pyridoxine It is quite unlikely to reach a toxic level of vitamin B6 from food sources alone Pyridoxine is the only water-soluble vitamin with significant toxicity. However, a toxic level can occur from long-term very high-dose supplementation. Neurologic symptoms (Neuropathy in feet and hands) occur at intakes above 500 mg/day, an amount nearly 400 times the Recommended Dietary Allowance (RDA). 30  Water soluble vitamins 1. Folic acid-Vitamin B9 2. Cobalamin-Vitamin B12 3. Vitamin C 4. Pyridoxine-Vitamin B6 5. Thiamine-Vitamin B1 6. Niacin-Vitamin B3 7. Riboflavin-Vitamin B2 8. Biotin-Vitamin B7 9. Pantothenic acid-Vitamin B5 31  Thiamine (vitamin B1) Thiamine pyrophosphate (TPP) is the biologically active form of the vitamin. Reaction that requires TPP TPP is formed by the transfer of a pyrophosphate group from adenosine triphosphate (ATP) to thiamine. Reaction Availability: peas, some that fresh fruits (such as requires bananas and oranges), TPP nuts, wholegrain bread, and liver. 32 33  Clinical indications for thiamine The oxidative decarboxylation of pyruvate (enzyme??) and α-ketoglutarate (enzyme??) , which plays a key role in energy metabolism of most cells, is particularly important in tissues of the CNS. In thiamine deficiency, the activity of these two dehydrogenase catalyzed reactions is decreased, resulting in decreased production of ATP and, therefore, impaired cellular function. Beriberi is the deficiency of vitamin B1: affect the cardiovascular system, resulting in a fast heart rate, shortness of breath, and leg swelling. Other symptoms that affects the nervous system, resulting in numbness of the hands and feet, confusion, trouble moving the legs, and pain. In rare, extreme cases of deficiency, beriberi may lead to a condition called Wernicke-Korsakoff syndrome. This syndrome is a form of brain damage resulting from severe thiamine deficiency. Symptoms may include memory loss or inability to form new memories. Beriberi mostly occurs in people with an alcohol use disorder. 34 35 Leg swelling 36  Water soluble vitamins 1. Folic acid-Vitamin B9 2. Cobalamin-Vitamin B12 3. Vitamin C 4. Pyridoxine-Vitamin B6 5. Thiamine-Vitamin B1 6. Niacin-Vitamin B3 7. Riboflavin-Vitamin B2 8. Biotin-Vitamin B7 9. Pantothenic acid-Vitamin B5 37 Niacin or Nicotinic acid (vitamin B1) The biologically active coenzyme forms are nicotinamide adenine dinucleotide (NAD+) and its phosphorylated derivative (NADP+). 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). Reduced form 38  Niacin or Nicotinic acid Distribution of niacin: Niacin is found in unrefined and enriched grains and cereal; milk; and lean meats, especially liver. 39  Niacin A deficiency of niacin causes pellagra (diarrhea, dermatitis, dementia, and possibly even death). Niacin is used in the treatment of hyperlipidemia: niacin strongly inhibits lipolysis in adipose tissue 40  Water soluble vitamins 1. Folic acid-Vitamin B9 2. Cobalamin-Vitamin B12 3. Vitamin C 4. Pyridoxine-Vitamin B6 5. Thiamine-Vitamin B1 6. Niacin-Vitamin B3 7. Riboflavin-Vitamin B2 8. Biotin-Vitamin B7 9. Pantothenic acid-Vitamin B5 41  Riboflavin (vitamin B2) The two biologically active forms of B2 are – Flavin mononucleotide (FMN) – Flavin adenine dinucleotide (FAD) Bacteria in the large intestine produce free riboflavin that can be absorbed by the large intestine in amounts that depend on the diet. More riboflavin is produced after ingestion of vegetable-based than meat-based foods. Riboflavin deficiency is extremely rare. 42 43  Water soluble vitamins 1. Folic acid-Vitamin B9 2. Cobalamin-Vitamin B12 3. Vitamin C 4. Pyridoxine-Vitamin B6 5. Thiamine-Vitamin B1 6. Niacin-Vitamin B3 7. Riboflavin-Vitamin B2 8. Biotin-Vitamin B7 9. Pantothenic acid-Vitamin B5 44  Biotin (vitamin B7) Biotin is a coenzyme in carboxylation reactions, in which it serves as a carrier of activated carbon dioxide. 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. 45 46  Biotin Biotin deficiency is fairly rare. However, some people such as pregnant women and people who drink high amounts of alcohol may develop mild deficiencies. Also, eating raw eggs on a regular basis can cause biotin deficiency, because raw egg whites contain a protein called avidin that binds to biotin, preventing the body from absorbing it. Cooking the eggs deactivates their avidin. Symptoms can include loss of hair, and a rough, red rash around body openings, including the eyes, nose, mouth, and anus, conjunctivitis can be also developed. Biotin-Avidin binding is used in Biotechnology !!!! 47  Water soluble vitamins 1. Folic acid-Vitamin B9 2. Cobalamin-Vitamin B12 3. Vitamin C 4. Pyridoxine-Vitamin B6 5. Thiamine-Vitamin B1 6. Niacin-Vitamin B3 7. Riboflavin-Vitamin B2 8. Biotin-Vitamin B7 9. Pantothenic acid-Vitamin B5 48  Pantothenic Acid (vitamin B5) Pantothenic acid is a component of CoA, which functions in the transfer of acyl. CoA contains a thiol group that carries acyl compounds as activated thiol esters. Examples of such structures are succinyl CoA, fatty acyl CoA, acetyl CoA, and fatty acid synthase complex. Eggs, liver, and yeast are the most important sources of pantothenic acid. Pantothenic acid deficiency is not well characterized in humans. 49 50 51 52  Reference Lippincott's Illustrated Reviews: Biochemistry Chapter 28 53