Water Soluble Vitamins - Dr. Ortiz - 2024-01.pdf
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Water Soluble Vitamins International Program of Medicine Dr. Maritza Roxana Garcia [email protected] Modified by Dr. Dávalos & Dra. Flores OBJECTIVES To know the shared characteristics of water soluble vitamins. To know their actions and food sources. To know the characteristics of their...
Water Soluble Vitamins International Program of Medicine Dr. Maritza Roxana Garcia [email protected] Modified by Dr. Dávalos & Dra. Flores OBJECTIVES To know the shared characteristics of water soluble vitamins. To know their actions and food sources. To know the characteristics of their deficiency/toxicity. GENERALITIES • With the exception of vitamin B9 & B12 , the body has no storage capacity for water-soluble vitamins. • As a consequence, they must be regularly supplied in the diet. • Any excess is excreted in the urine. B-complex vitamins • B-complex vitamins are essential for normal metabolism and serve as coenzymes in many carbohydrate, fat, and protein metabolism reactions. The greater the caloric intake, the larger the requirement for B vitamins. Vitamin B1 • In its active form, thiamine pyrophosphate (TPP), vitamin B1 is a coenzyme participating in oxidative decarboxylation • Eg. pyruvate dehydrogenase & αketoglutarate and also in the metabolism of branched-chain amino acids. • It is also a coenzyme for transketolase in the pentose phosphate pathway (PPP) Sources of vitamin B1 Deficiency of vitamin B1 Thiamine depletion can occur quickly within approximately 14 days. Symptoms: loss of appetite, constipation, and nausea (early) • They may progress to depression, peripheral neuropathy, and unsteadiness. • Further deterioration results in mental confusion, ataxia, and loss of eye coordination. (Classic triad) • This combination, often seen in alcoholic patients, is known as Wernicke–Korsakoff psychosis. Deficiency of vitamin B1 Beriberi was the first-discovered deficiency disease. • “dry” (without fluid retention) • “wet” (associated with cardiac failure with edema) • Characterized primarily by neuromuscular symptoms (neuropathy & muscle wasting) • Populations relying exclusively on polished rice for food, may also be seen in the elderly or in low-income groups with poor diet. Vitamin B2 Vitamin B 2 (riboflavin) is required for Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) synthesis. • The FMN and the FAD are formed by transfer of phosphate and adenosine monophosphate from ATP, respectively. • They are coenzymes of the oxidoreductases and participate in redox reactions. Riboflavin is transformed to FMN and FAD by the action of riboflavin kinase and FAD synthase. synthesis of niacin (B3) from tryptophan**** FAD and FMN act as electron carriers in several oxidation-reduction (redox) reactions involved in energy production, cellular antioxidant function, and in numerous metabolic pathways. Role in folate and related one-carbon metabolism Riboflavin is linked to the metabolism of iron & B-vitamins (B6, B9, B12) involved in homocysteine remethylation and transsulfuration. The flavoenzyme methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which serves as a methyl group donor in the conversion of homocysteine to methionine. Sources of vitamin B2 • • • Eggs, organ meats (such as kidneys and liver), lean meats, and low-fat milk. Green vegetables (such as asparagus, broccoli, and spinach). Fortified cereals, bread, and grain products. Deficiency of vitamin B2 • Inflammation of the corners of the mouth (angular stomatitis), inflammation of the tongue (glossitis), and scaly dermatitis. • To determine riboflavin erythrocyte glutathione reductase status, activity is measured. Vitamin B3 Vitamin B3 (niacin) is required for NAD + and NADP + synthesis related to energy expenditure. • Niacin is a generic name for nicotinic acid or nicotinamide, both of which are essential nutrients. • Coenzyme nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+), both of which participate in oxidoreductase-catalyzed reactions. B2 & B6*** Sources of vitamin B3 Deficiency of vitamin B3 • Superficial glossitis but may progress to pellagra à characterized by dermatitis, sunburn-like skin lesions in areas of the body exposed to sunlight and to pressure, diarrhea and dementia. • Certain drugs, such as the antituberculosis drug isoniazid, predispose to niacin deficiency. • In contrast, very high doses of niacin can cause hepatotoxicity. Vitamin B5 (Pantothenic acid) Pantothenic acid forms part of the molecule of coenzyme A. • • • The intestinal flora produces pantothenic acid. Red blood cells carry pantothenic acid throughout the body. Most pantothenic acid in tissues is in the form of CoA. Vitamin B5 CoA is essential for fatty acid synthesis and degradation, transfer of acetyl and acyl groups, and a multitude of other anabolic and catabolic processes. Sources of pantothenic acid Almost all plant- and animal-based foods contain pantothenic acid in varying amounts. Some of the richest dietary sources are beef, chicken, organ meats, whole grains, and some vegetables. Deficiency Vitamin B5 • Deficiency of pantothenic acid is very rare. • Symptomsà burning feet and numbness of toes, headache, Fatigue, irritability, restlessness, disturbed sleep, nausea, vomiting, stomach & muscle cramps. • No toxicity has been reported. Vitamin B6 Vitamin B6 (pyridoxine) participates in carbohydrate and lipid metabolism and is particularly important for amino acid metabolism. • • Pyridoxine is the major form of vitamin B6 in the diet, and pyridoxal phosphate (PLP) is its active form. It is absorbed in the jejunum. B2*** Vitamin B6 Pyridoxine is required for the synthesis of the neurotransmitters like serotonin and noradrenaline, sphingosine, a component of sphingomyelin and sphingolipids, and heme. Pyridoxine requirements increase with high protein intake (role in amino acid metabolism). Sources of vitamin B6 Vitamin B 6 is present in a wide variety of foods, such as fish, beef, liver, poultry, potatoes, and fruits (but not citrus fruits). Deficiency of vitamin B6 Pyridoxine deficiency causes neurologic symptoms and anemia. • Mild à irritability, nervousness, and depression. • Severeà peripheral neuropathy, convulsions, and coma. • Sideroblastic anemia. • Dermatitis, cheilosis, and glossitis. Decreased levels are observed in alcoholism, obesity, and malabsorption states, as well as in end-stage renal disease and in autoimmune conditions. Vitamin B7 (Biotin) • Biotin (vitamin H) serves as a coenzyme in multienzyme complexes involved in carboxylation reactions in lipogenesis and gluconeogenesis as well as in the catabolism of the branched-chain amino acids. Sources of vitamin B7 • • • • Biotin is normally synthesized by the intestinal flora, and this meets most of the body's requirements Meat, fish, eggs, and organ meats (such as liver). Seeds and nuts. Certain vegetables (such as sweet potatoes, spinach, and broccoli). Biotin deficiency • Symptoms include depression, hallucinations, muscle pain, hair loss, and dermatitis. • Consumption of raw eggs can cause biotin deficiency because the egg-white protein avidin combines with biotin, preventing its absorption. Vitamin B9 (folic acid) • Folic acid exists in a number of derivatives collectively known as folates. • It participates in single-carbontransfer reactions, such as methylation (important in both metabolism and regulation of gene expression), and in the synthetic pathways of choline, serine, glycine, and methionine. Folic acid is also necessary for the synthesis of purines and pyrimidine thymine and, thus, for the synthesis of nucleic acids. Sources of vitamin B9 • Folic acid is present in liver, yeast, and green leafy vegetables (spinach) and fruits, including citrus fruits. • Its sources also include folic acid– enriched cereals and grains. Vitamin B9 (folic acid) • • Not surprisingly, rapidly dividing cells have high requirements for folate because it’s necessary for the synthesis of purines and pyrimidine thymine (DNA synthesis). Structural analogs of folate exhibit selective toxicity toward rapidly growing cells such as bacteria and cancer cells à drugs known as the folic acid antagonists, which are used as antibiotics (e.g., trimethoprim) and anticancer agents (methotrexate). Deficiency of vitamin B9 • • • • Folate deficiency is one of the commonest vitamin deficiencies. Causesà inadequate intake, impaired absorption (alcoholism, malabsorption), impaired metabolism (dialysis, and liver disease), and increased demand (pregnancy & lactation). Folate deficiency increases the risk of neural tube defects, low birth weight, and premature birth. In infants, it results in a decreased growth rate. Deficiency of vitamin B9 • • • Folate deficiency in adults causes megaloblastic anemia. The hematologic abnormalities can’t be distinguished from vitamin B 12 deficiency. No neurological symptoms. In addition, deficiency of folate also contributes to hyperhomocysteinemia. Vitamin B12 (Cobalamin) • • • Has a complex ring structure like the porphyrin of heme. The iron at the center of the heme ring is replaced by a cobalt ion (Co 3+ ). Essential for the chelation of the cobalt ion and in methionine synthesis. Vitamin B12 • • Vitamin B12 participates in nucleic acid synthesis, in the production of erythrocytes, and in the recycling of folates. Together with folate and vitamin B6, it controls homocysteine metabolism, where it is a cofactor for methionine synthase, which converts homocysteine to methionine. It participates in the synthesis of the methyl donor molecule, Sadenosylmethionin. Food sources Vitamin B12 Vitamin B12 is synthesized solely by bacteria. It is absent from all plants but is concentrated in the livers of animals, fish and dairy products in three forms: methylcobalamin, adenosylcobalamin, and hydroxocobalamin. Vegans are therefore at risk of developing a dietary deficiency of vitamin B12 . Vitamin B12 deficiency Vitamin B 12 deficiency is characterized by megaloblastic anemia, fatigue, constipation, weight loss, diarrhea, and neurologic symptoms. • • Pernicious anemia, an autoimmune condition that results in gastric atrophy and the lack of intrinsic factor (can also be caused by gastric surgery). Pernicious anemia affects 1%–3% of older adults. Vitamin C • Vitamin C serves as a reducing agent. • Its active form is ascorbic acid, which is oxidized during the transfer of reducing equivalents, yielding dehydroascorbic acid. Vitamin C • Synthesis of epinephrine, in steroidogenesis, in the degradation of tyrosine, in the formation of bile acids, and also in the synthesis of L-carnitine. • Improves absorption of nonheme iron (reduces iron into its ferrous fe2 state) and participates in bone mineral metabolism. • • Its prime function is to maintain metal cofactors in their lower valence states (e.g., Fe2+ and Cu2+). Regeneration of another antioxidant vitamin, α-tocopherol. E- reduced antioxidants In the synthesis of collagen, it’s required specifically for the hydroxylation of proline & lysine. Sources of vitamin C • Humans cannot synthesize ascorbic acid; therefore, it is an essential nutrient. • Vitamin C is labile: it’s easily destroyed by oxygen, metal ions, increased pH, heat, and light. • Citrus, soft fruits, tomatoes, and peppers are rich sources of vitamin C. Vitamin C deficiency • Scurvy à capillary fragility, causing subcutaneous and other hemorrhages, muscle weakness, soft, swollen, bleeding gums, loosening of teeth, poor wound healing, and anemia. • • Fatigue, malaise, and depression also occur. The inability to maintain bone matrix in association with demineralization results in osteoporosis. Vitamin C deficiency • Immune functionà reduction in immunocompetence • prevent the common cold & role in cancer prevention ?? • Vitamin C is certainly required for normal leukocyte function, and leukocyte vitamin C levels drop precipitously during the stress caused by either trauma or infection. • Elderly individuals are at increased risk of deficiency, as are smokers and infants fed evaporated or boiled milk. Vitamin C toxicity • There is no evidence that vitamin C taken in excess is toxic. • Theoretically, because it is metabolized to oxalate, there is a risk of the development of renal oxalate stones in susceptible individuals. • However, this has not been substantiated in practice. Dietary supplementation of vitamins • Supplementation of some vitamins results in a clear health benefit. • This includes supplementation of folic acid to women who are pregnant or are planning pregnancy to prevent neural tube defects (4 weeks before and 8 weeks after conception). • Vitamin D provision to people living in areas of low sunlight has also been beneficial and in low BMD. • Because supplementation of folic acid and vitamin B 6 and B 12 lowers the plasma homocysteine concentration, it has been suggested that it could be beneficial for the prevention of cardiovascular disease. • High-dose vitamin supplementation may be harmful, an example is the reduction of bone mineral density, hepatotoxicity, and teratogenicity associated with high doses of vitamin A. Vitamin Thiamine (TPP, thiamine pyrophosphate) B1 Riboflavin B2 Function • Cofactor for dehydrogenase enzyme reactions • Pyruvate dehydrogenase • Α-ketoglutarate dehydrogenase • Transketolase • Branched-chain ketoacid dehydrogenase • Component of flavins (FAD & FMN), cofactor in redox reactions Deficiency • • • Impaired glucose breakdownà ATP depletion Wernicke Korsakoff syndrome (confusion, ophthalmoplegia & ataxia + confabulation, personality changes, memory loss) Dry & Wet Beriberi (polyneuropathy, symmetrical muscle wasting dilated cardiomyopathy and edema) • Cheilosis (inflammation of lips, scaling and fissures of mouth corners) • Corneal vascularization S u m m a r y Vitamin Niacin Function • • B3 Pantothenic acid B5 • • Component of NAD+, NADP+ - used in redox reactions. Derived from tryptophan Synthesis requires B2 & B6 Tx. Dyslipidemias = lowers VLDL & raises HDL • Essential component of coenzyme A (cofactor for acyl transfers) & fatty acid synthase. • Tx. Alopecia Deficiency • • Glossitis SEVEREà Pellagra • Hartnup disease • Malignant carcinoid syndrome • Isoniazid SYMTOPMS • Diarrhea • Dementia • Dermatitis (casal necklace) hyperpigmentation of sun exposed limbs. • Rare except in people who have other nutrient deficiencies S u m m a r y Vitamin Pyridoxine (PLP – pyridoxal phosphate) B6 Biotin B7 Function • • Cofactor for transamination, decarboxylation reactions, glycogen phosphorylase. Synthesis of cystathionine, heme niacin, histamine and neurotransmitters including serotonin, epinephrine and norepinephrine, dopamine and GABA) • Cofactor carboxylation enzymes. • Pyruvate carboxylase • Acetyl-coA carboxylase • Propionyl-coA carboxylase • Methylcrotonyl-CoA carboxylase Deficiency • • • • • • • • Convulsions Hyperirritability Peripheral neuropathy • Isoniazid and OC Sideroblastic anemia • Impaired hemoglobin synthesis, iron excess Rare Dermatitis Alopecia Caused by AB & raw egg whites S u m m a r y Vitamin Folate (THF – tetrahydro folic acid) Function • • B9 Cobalamin B12 • • Coenzyme for 1-carbon transfer/methylation reactions) Synthesis of NITROGENOUS BASES in DNA & ARN Absorbed in JEJUNUM Store in liver Deficiency • • • • • • • Cofactor methionine synthase & methylmanolyl-CoA mutase. • DNA SYNTHESIS • Animal products • Store in LIVER Macrocytic megaloblastic anemia Glossitis NO neurologic symptoms HIGH homocysteine, NORMAL methylmalonic acid Caused by drugs à phenytoin, sulfonamides, methotrexate NEURAL TUBE DEFECTS • CAUSESà Malabsorption, lack of Intrinsic factor, NO terminal ILEUM, insufficient intake. • Macrocytic megaloblastic anemia • Abnormal myelin leading to demyelinating processes. à LEAD TO IRREVERSIBLE NERVE DAMAGE. S u m m a r y Vitamin Ascorbic acid Function • • • C • Antioxidant Reduction of iron into FE2+ (better absorption) Collagen synthesis (hydroxylation of proline and lysine) Conversion of dopamine into NE. Deficiency • SCURVY - COLLAGEN SYNTHESIS DEFECT • Swollen gums • Bruising • Petechia • Hemarthrosis • Anemia • Poor wound healing • Perifollicular and subperiosteal hemorrhages • corkscrew hair • POOR IMMUNE response S u m m a r y Resources • Baynes, J., & Dominiczak, M. H. (2019). Medical biochemistry. Elsevier Health Sciences. Chapter 7, 75-91 • https://www.ncbi.nlm.nih.gov/books/NBK225480/
