Micronutrients (Vitamins & Minerals) PDF 2024

Micronutrients (Vitamins & Minerals) Asmare Amuamuta (Ph.D.) Assoc. Professor of Biochemistry & Bioclinical Sciences, CMHS Bahir Dar University...

Micronutrients (Vitamins & Minerals) Asmare Amuamuta (Ph.D.) Assoc. Professor of Biochemistry & Bioclinical Sciences, CMHS Bahir Dar University E-mail: [email protected] ) NOV 2024 1  Vitamins  Vitamins are organic (carbon) compounds needed for normal function, growth and maintenance.  Vitamins act as coenzymes (they don’t do anything by themselves).  They are not a source of calories. 2 The Nature of Vitamins Effect of packaging on  Nutritional Value lost by: nutrient loss in milk.  Light  Heat  Oxidation  Bacteria  Enzymes  Insects 3  Fat Soluble Vitamins  Stored in the liver and fatty tissues.  Daily intake not required.  Deficiency occurs only after prolonged deprivation.  Can become toxic if excessive amounts are consumed. 4 Fat soluble vits  Vit.A – involved in reproduction, mucosal integrity, vision and antioxidant roles !  Vit.D –obtained from diet or synthesized on the skin (by using sun light) from cholesterol and regulates Ca:P ratios in the body.  Vit.E – involved as antioxidant roles.  Vit.K – contributes to blood clotting. 5 Vitamin A Lots of double bonds (good anti- oxidant). 6  Vitamin A  Carrotinoids are major sources  Stored in liver  Has antioxidant roles, in cell division, mucosal integrity and vimp. ision/sight.  Deficiency states ch’d by:  Hyperkeratosis of the skin  Night blindness  Other conditions 7  Vitamin D  Also known as ‘calciferol/calcitriol’ due to its role in calcium absorption/reabsorption.  Can be stored in the body. Sources:-  It is the only fat soluble vitamin that can be synthesized in the body (with the presence of sunlight from cholesterol)  Plant & animal (fish oils, salmon, animal livers, eggs, butter, cereals & fortified milk ) are main sources. Function: Main role is to maintain Ca+2 and P- levels (normal calcification of bones & teeth) in the body. Note: Vitamin D2 (ergocalciferol) is also known as plant vitamin D obtained through dietary sources & vitamin D3 (cholecalciferol) is produced in skin by UV…both have same metabolic effect ! 8  Fig. Vit.D synthesis in the body. Fig. Activation of Vitamin D. 9 Vit.D/calcitriol and Ca+2/P metabolism 10  Vit. D deficiency  Children & elderly (osteomalacia/osteoporesis) are at risk (lack of enough sunlight). ‘Rickets’ is caused by lack of sunlight or vit D (but could also happen due to insufficient calcium intake) in children. Note: Vitamin D linked to extraskeletal roles !! 11 Vitamin D: Toxicity  Long-term ingestion of excessive amounts causes toxicity  Hypertension, weakness, fatigue, headache, many others  GI tract effects  CNS effects Mosby items and derived items © 2005, 2002 by Mosby, Inc. Vitamin E/ ά-tocopherol 13  Vitamin E…  Fat soluble (d/t tocopherols) Sources:  Dietary plant sources  Fruits, grains, cereals, vegetables, oils, wheat germ  Animal sources  Eggs, chicken, meats, fish Function: Exact biologic function of vitamin E is unknown but believed to act as an antioxidant. Mosby items and derived items © 2005, 2002 by Mosby, Inc. Vitamin K  Fat soluble  Three types: K1, K2, K3  Dietary sources of K1/Phylloquinone  Green leafy vegetables (cabbage, spinach), meats, milk  Vitamin K2 synthesized by intestinal flora Mosby items and derived items © 2005, 2002 by Mosby, Inc. Vit K… 16 Vitamin K.. Functions:  Essential for synthesis of blood coagulation factors in the liver  Vitamin K–dependent clotting factors:  II (prothrombin)  VII  IX X Mosby items and derived items © 2005, 2002 by Mosby, Inc. Vit. K in Blood Clotting:  The vitamin K–dependent posttranslational carboxylation of glutamyl residues that forms γ-carboxyglutamate (by γ- glutamyl carboxylase) on 4 major proteins (factor II or prothrombin, VII, IX, and X) required for coagulation of blood. Fig. Blood clotting cascades 18 Vitamin K.. Vit K indications:  Dietary supplementation  Treatment of deficiency states (rare)  During antibiotic therapy  Newborn infants  Malabsorption conditions  To reverse the effects of certain anticoagulants (warfarin, heparin..) Mosby items and derived items © 2005, 2002 by Mosby, Inc.  Water Soluble Vitamins  Can dissolve in water B1 (Thiamin)-TPP  Excessive amounts excreted in the urine, not stored in the B2 (Riboflavin)-FAD+, FMN body B3 (Niacin) –NAD+, NADP+ PantothenicAcid/B5 -CoA  With the exception of B6 (Pyridoxine)-PLP vitamin C (ascorbic acid), B7 (Biotin) -Biotin water-soluble vitamins are B9 (Folic Acid) - THF members of the B-complex B12 (Cobalamin) and most of them act as co- enzymes! 20 21  Water Soluble Vitamins..  Vitamin B1 -Thiamine 22  Thiamine.. Function:- Involved in carbohydrate metabolism in metabolic pathways including Kreb’s cycle (as TPP). i.e. Pyruvate conversion to Acetyl-CoA by PDH complex enzyme !  As TDP/TPP, thiamin functions in energy transformation as a coenzyme of the pyruvate dehydrogenase (PDH) complex, the α-ketoglutarate dehydrogenase complex, and the branched chain α-keto acid dehydrogenase complex rxns.  Maintains integrity of peripheral nervous system, CVS and GI tracts. 23 Deficiency of thiamine  Def. states called Beriberi (white rice d+).  Ch’d by brain lesions, polyneuropathy of peripheral nerves, serous effusions, cardiac anatomic changes..  Wernicke’s encephalopathy  Cerebral beriberi Mosby items and derived items © 2005, 2002 by Mosby, Inc. Causes of Thiamine Deficiencies  Poor diet  Extended fever, hyperthyroidism, liver disease, alcoholism  Malabsorption conditions  Pregnancy and breast-feeding Mosby items and derived items © 2005, 2002 by Mosby, Inc. Vit B2- riboflavin  Water soluble  Food sources  Leafy green vegetables, eggs, nuts, meat, etc 26 Vit B2- riboflavin..  Two co-enzyme forms FMN & FAD.  Energy metabolism (a variety of Oxidation-Reduction Reactions) ! Note: Flavins can act as oxidizing agents because of their ability to accept a pair of H- atoms. 27 e.g. Role of flavoproteins (FAD/FMN)in the electron transport chain (ETC)/tissue respiration 28 Functions…  In the oxidative decarboxylation of pyruvate and α- ketoglutarate  Succinate dehydrogenase is a FAD flavoprotein  In fatty acid oxidation (fatty acyl CoA dehydrogenase)  Sphinganine oxidase, in sphingosine synthesis, requires FAD  As a coenzyme for an oxidase such as xanthine oxidase  In Vit.B6 metabolism; pyridoxine phosphate oxidase—which converts pyridoxamine phosphate (PMP) and pyridoxine phosphate (PNP) to pyridoxal phosphate (PLP).  Synthesis of an active form of folate/5-methyl THF requires FADH2  In try convertion to niacin  In choline catabolism. 29  B2 Deficiency Causes  Alcoholism is a major cause  Deficiency also caused by:  Intestinal malabsorption  Long-term infections and liver disease  Malignancy and probenecid therapy Mosby items and derived items © 2005, 2002 by Mosby, Inc. Vit B2 Indications  Dietary supplement  Treatment of B2 deficiency  Microcytic anemia  Acne and migraine headaches  Many other uses Mosby items and derived items © 2005, 2002 by Mosby, Inc.  Niacin (B3)  Food sources  Meats, beans, liver, yeast, wheat  The body can make niacin from the amino acid tryptophan.  Role: Energy metabolism (glycogenolysis, lipid/protein metab, tissue respiration) and Fig. Niacin purine metabolism  Supports nervous and digestive system and promotes healthy skin. 32 Two coenzyme forms NAD & NADP (take part in energy metabolism) NAD+ NADP+ 33 Functions :-  Approximately 200 enzymes, primarily dehydrogenases, require the coenzymes NAD+ and NADP+, which act as a hydrogen donor or electron acceptor. 34 Functions.. Some of the oxidative reactions in which NAD+ participates and is reduced to NADH include: -Glycolysis -Oxidative decarboxylation of pyruvate -Oxidation of acetyl CoA in the TCA cycle -β-oxidation of fatty acids -Oxidation of ethanol The NADP+/NADPH used in a variety of reductive biosyntheses; -Fatty acid synthesis -Cholesterol and steroid hormone synthesis -Oxidation of glutamate & folate metabolism -Synthesis of deoxyribonucleotides (precursors of DNA) -Regeneration of glutathione, vitamin C, and thioredoxin 35 Vitamin B3 (Niacin)Deficiency  Niacin deficiency is ch’d by:  Mental: various psychotic symptoms  Neurologic: neurasthenic syndrome  Cutaneous: crusting, erythema  Mucous membrane: oral, vaginal, and urethral lesions  GI: diarrhea or bloody diarrhea Mosby items and derived items © 2005, 2002 by Mosby, Inc.  Niacin Def..  Like thiamine, which was discovered through its deficiency disorder ‘beriberi’, niacin was discovered through the condition ‘pellagra’ (ch’ed by the three Ds—dermatitis, dementia, diarrhea) in humans and a similar condition, called ‘black tongue’, in dogs ! And death (as 4th D). 37 Panthothenic acid- VitB5(Part of CoA)  Pantothenic acid consists of β-alanine and pantoic acid joined by a peptide bond/amide linkage. Fig. Pantothenic acid and CoA (coenzyme form) 38 Fig. CoA Fig. The structure of CoA 39 CoA forms thio esters with carboxylic acids and can transfer the acetyl or acyl groups, typically 2 to 13 carbons, for various cellular reactions: - Carbohydrate metabolism -FA synthesis (formation of condensation of acetyl-CoA with activated CO2 to form malonyl CoA) -Cholesterol and ketone bodies synthesis (acetyl CoA and acetoacetyl CoA reaction to form HMG CoA) -Phospholipid and sphingomyelin production 40  Vit B6 (Pyridoxine)  Sources  Whole grains, wheat germ, nuts, yeast  Fish and organ meats Vit B6 – Pyridoxine (PLP as the coenzyme form) Functions:  Involved as a neurotransmitter, and immune system  Co-enzyme in > 100 reaction (important in the metabolism of amino acids/transamination reactions mainly and also fatty acids metabolism) 41 Pyridoxine PLP 42  Vit B6 Functions  Necessary for many metabolic functions  Protein, lipid, and carbohydrate utilization  Conversion of tryptophan to niacin Necessary for integrity of peripheral nerves, skin, mucous membranes, hematopoietic system Mosby items and derived items © 2005, 2002 by Mosby, Inc. Biotin – VitB7  Functions in energy metabolism as a coenzyme that carries CO2 (carboxylation rxns)  Can be synthesized by bacteria in the GI tract.. 44  Biotin Plays a role in gluconeogensis, metabolism of fatty acids and the breakdown of amino acids. Table: 4 Carboxylases that use biotin in cells 45 Fig. The role of Biotin for PC enzyme Fig. The oxidation of propionyl CoA by PCC & the role of Biotin 46 Folate – Folic acid –Vit B9  Folate is made up of three distinct parts (as shown below), all of which must be present for vitamin activity.  Coenzyme form is THF  Important in metabolism and important in DNA synthesis  Folate’s and vitamin B12’s discovery resulted from the search to cure the disorder megablastic anemia, a problem in the late 1870s and early 1880s. 47 Functions and MoA:-  THF functions in the body as a coenzyme in both the mitochondria and cytoplasm to accept one-carbon groups in amino acid synthesis (metabolism) and DNA synthesis (purine and pyrimidine synthesis).  The THF derivatives, which participate in a variety of reactions… 48 DNA (Purine and Pyrimidine) Synthesis  Synthesis of new cells with short life spans, such as enterocytes, is particularly dependent on adequate levels of folate.  In purine synthesis; Folate as 10-formyl THF is needed for purine (adenine and guanine) ring formation.  In pyrimidine synthesis; thymidylate synthetase uses 5,10- methylene THF to convert dUMP to dTMP (used for DNA synthesis) and DHF.  To regenerate 5,10-methylene THF, DHF is converted by dihydrofolate reductase (DHFR) to THF in a reaction requiring NADPH.  Both thymidylate synthetase and DHFR are active enzymes in cells undergoing cell division. 49 Fig. The role of Folate in pyrimidine synthesis used for DNA synthesis 50 Deficiency disorders: Megaloblastic/Macrocytic Anemia:  Megaloblastic Anemia (MA) is deficiency of folate that may also occur with the def. of vitamin B12 and interferes with normal cell division. Note: synergistic relationship exists between folate and vitamin B12/cobalamin !  MA characterized by increased mean cell volume (MCV), and hypersegmentation (increased lobes) of white blood cells (neutrophils) occurs, along with decreased blood cell counts. 51  Folate/B12 deficiency ! Fig. Genesis of normal RBCs and megaloblastic anemia in Folate/Vit.B12 deficincy 52 Methionine regeneration from homocysteine involves folate as 5-methyl THF and Vit B12 synergistic action. 53 Other D+es associated to Folate def… Occlusive vascular diseases including cerebral or peripheral and coronary artery disease (associated to hyperhomocysteinemia). Increased DNA strand breaks and intiations of some cancers (e.g colon cancers) CNS/neural devt defects (e.g. ‘Spina bifida’) due to defective choline synthesis (a major component of cell membranes). 54 Folate def & neural tube defect.. 55 Vit B12 - Cyanocobalamine  Vit. B12/Cobalamin contains the corrin nucleus (a macrocyclic ring made of 4 reduced pyrrole rings linked together) and in the center of the corrin is an atom of cobalt (Co) to which is attached, at almost right angles, is the nucleotide 5,6- dimethylbenzimidazole. 56 Cobalamine.. 57 Functions and MoA:-  The reaction requiring methylcobalamin as a coenzyme: -Methylcobalamin is needed in methionine synthesis or regeneration. i.e. cobalamin bound to the methionine synthase (also called homocysteine methyltransferase) picks up the methyl group from 5-methyl tetrahydrofolate (THF), forming methylcobalamin bound to methionine synthase and THF. 58 MoA…  Because the formation of 5-methyl THF is irreversible, a vitamin B12 deficiency traps body folate in the 5-methyl form, in what is known as the methyl-folate trap hypothesis. This hypothesis helps explain in part the synergism between folate and vitamin B12 !!  DNA and RNA synthesis (RBC devt, maintains and protects nerve fibers and promotes their normal growth )! 59 60 Vit. B12.. -The 2nd of the vitamin B12–dependent reactions requires adenosylcobalamin (oxidation of L-Methyl malony CoA) catalyzed by a mutase enzyme called methylmalonyl CoA mutase ! [Imp. for metabolic pathways including fat and CH2Os metabolism] ! 61 Deficiency disorders:-  Megaloblastic Anemia  Most deficiency signs and symptoms are of neurologic and hematologic origin; some signs and symptoms include skin pallor, fatigue, shortness of breath, palpitations, insomnia, tingling and numbness (paresthesia) in extremities, abnormal gait, loss of concentration, memory loss, disorientation, swelling of myelinated fibers, and possibly dementia. Vit B12 deficiency secondary to malabsorption could be caused by: - Pernicious anemia (autoimmune condition in which the body produces Abs that attack gastric parietal cells and decrease IF). - Atrophic gastritis and gasterectomy - Achlorhydria (reduced HCl production) - Increased use of medications for GERD - Ileitis (inflammation of the Ileum) and in elderly people  Methylmalonic Aciduria 62 Vitamin C (Ascorbic Acid)  The human being is one of the few mammals unable to synthesize vitamin C, also known as ascorbic acid or ascorbate.  Other animals unable to synthesize vitamin C include primates, guinea pigs, and some birds.  The inability to synthesize vitamin C results from the lack of gulonolactone oxidase (the final enzymatic reaction in Vit. C synthesis. 63 Fig. The interconversion of ascorbate and dehydroascorbate 64 Functions and MoA:-  Acts in oxidation-reduction reactions (‘anti-oxidant activity’)  Required for several metabolic activities -Collagen synthesis; hence maintenance of bone, teeth, capillaries & connective tissue/tissue repair like skin. -Carnitine and tyrosine synthesis -Folic acid metabolism and erythropoiesis -Enhances absorption of iron (Fe+2) -Required for the synthesis of lipids, proteins and steroids. *Aids in resistance to infections e.g. Colds 65 Collagen synthesis:-  Ascorbate functions in a number of hydroxylation reactions (3 hydroxylation reactions; prolyl 4-hydroxylase, prolyl 3- hydroxylase and lysyl hydroxylase rxns ) requiring vitamin C are necessary for collagen synthesis or triple helix configuration. 66 Antioxidant activity:-  Vitamin C functions in a general capacity as a reducing agent or electron donor and thereby has antioxidant activity.  Ascorbic acid acts as a reducing agent in aqueous solutions such as the blood and within cells. Examples of reactive oxygen/N species that vitamin C may reduce include: -Hydroxyl radical ( OH) -Hydroperoxyl radical (HO2 ) -Superoxide radical (O 2 ) -Alkoxyl radical (RO ) -Peroxyl radical (RO2 ) 67  Once formed, free radicals and reactive species attack nucleic acids in DNA, PUFAs in phospholipids, and proteins in cells.  Ascorbic acid has been shown to interact with oxidants in the aqueous phase before they initiate damage, especially to cell lipids.  Furthermore, ascorbic acid appears to be superior to other water-soluble antioxidants such as bilirubin, uric acid, and protein thiols. 68 Deficiency:- Deficient vitamin C intakes result in the deficiency condition known as scurvy (when plasma vitamin C concentrations drop to