Vitamins and Nutrition Vitamin – Coenzyme – Cofactor – Prosthetic group – Water-Soluble Vitamins Name Function Deficiency Vitamin B1 (thiamin) Precursor to coenzyme thiamin pyrophosphate, which is required for oxidative decarboxylation reactions Beriberi – muscle weakness, loss of reflexes, numbness, depression Vitamin B2 (riboflavin) Precursor to FAD and FMN, which are prosthetic groups used for redox reactions. Not named – photophobia, proliferation of capillaries in the eye, dermatitis Vitamin B3 (niacin) Precursor to NAD and NADP, which are coenzymes used for redox reactions. Pellegra – weight loss, digestive disorders, dermatitis, depression, dementia Vitamin B5 (Pantothenic acid) Precursor to Coenzyme A Not named – neurological and digestive problems Vitamin B6 (pyridoxal and related compounds) Precursor to pyridoxal phosphate, which is a prosthetic group for amino acid metabolic enzymes and for glycogen phosphorylase Not named – dermatitis, neuropathy, altered free amino acid levels, depression. Vitamin B12 (cobalamin) Precursor to coenzymes used for one-carbon transfer reactions Pernicious anemia – enlarged fragile erythrocytes, neurological disorders Folic acid Precursor to coenzyme tetrahydrofolate, which is used for one-carbon transfer reactions Megaloblastic anemia – enlarged fragile erythrocytes, neural tube defects, neurological disorders Biotin Prosthetic group for several carboxylase enzymes Not named – depression, hallucinations, muscle pain, dermatitis, immunodeficiency Vitamin C (ascorbic acid) Coenzyme for hydroxylase enzymes Scurvy – defective collagen synthesis, dementia Fat-Soluble Vitamins Name Function Deficiency Vitamin A (retinol and β-carotene) Precursor visual pigment retinal and to retinoic acid signaling molecules involved in cellular differentiation Not named – night-blindness, blindness, developmental abnormalities, keratinization of epithelial tissues. Vitamin D (ergocalciferol and cholecalciferol) Precursor to 1α, 25-dihydroxyvitamin D, a signaling molecule involved in calcium absorption and homeostasis, and in regulation of cellular differentiation Rickets and Osteomalacia – softening of the bones Vitamin E (α-tocopherol) Antioxidant, especially in erythrocytes. Not named – anemia, and possibly other effects Vitamin K (menadione and related compounds) Precursor to Vitamin K coenzyme used for synthesis of γ-carboxyglutamate residues, especially in clotting factor proteins Hemorrhagic disease of the newborn, Hemorrhagic syndrome – deficient blood clottingNiacin (Vitamin B3) NNCH3HNO3NOHONicotine Nicotinic acidNHNONH2IsoniazidNNH2ONicotinamideNHNH3OO OOHOHCH2NOPOOOOOHOHCH2ONNNNNH2POONH2OOOPOOOOHOHCH2NOPOOOOOHCH2ONNNNNH2POONH2ONicotinamide adeninedinucleotide[NAD]Nicotinamide adeninedinucleotide 2´-phosphate[NADP]NNH2ORH2 electrons+1 protonNNH2ORH H2 electrons+1 protonOxidizedNAD(P)ReducedNAD(P)HAlcohol Dehydrogenase HNNSSZnHOHNHNOHCys46His67Ser48Cys174His51SubstratebindingNOOOHHNH2ORHHNNSSZnCONHNOCys46His67Ser48Cys174His51HH3CHHHProtonabstractionNOOOHNH2ORHHNNSSZnCONHNOCys46His67Ser48Cys174His51HH3CHHHHHydridetransferNOOOHNH2ORHHHNNSSZnCONHNOCys46His67Ser48Cys174His51HH3CHHHHNNSSZnHOHNHNOHCys46His67Ser48Cys174His51SubstratedissociationRiboflavin (Vitamin B2) NNNNHOOH3CH3COHOHHOOH OPOOOOOHOHCH2ONNNNNH2POONNNNHOOH3CH3COHOHHOOPOOONNNNHOOH3CH3COHOHHORiboflavin(Vitamin B2)Flavinmononucleotide[FMN]Flavin adeninedinucleotide[FAD] NNNNHOOH3CH3CR1 electron+1 proton1 electron+1 protonNNNNHOOH3CH3CRHNNNNHOOH3CH3CRHH1 electron+1 proton1 electron+1 proton•Fully oxidized Partially reduced Fully reducedIsoalloxazine Ring Ascorbic Acid (Vitamin C) 2 electrons +2 protons2 electrons +2 protonsHOOHOOHO OHAscorbic acid(Vitamin C)Dehydroascorbic acidHOOHOOO OThiamin (Vitamin B1) Thiamin(Vitamin B1)OHNNNSH3CNH2H3CHThiamin pyrophosphateO POOOPOOONNNSH3CNH2H3CH Thiamin pyrophosphateOPOOOPOOONNNSH3CNH2H3CHThiamin pyrophosphatecarbanionOPOOOPOOONNNSCH3CNH2H3CH3CCCOOOPyruvate++HHydroxyethylThiamin pyrophosphateOPOOOPOOONNNSH3CNH2H3CCHOCH3CO2+ Pantothenic Acid (Vitamin B5) OHCH2C CH3H3CCHHOCONHH2C CH2COOHPantoicacid!-alanineOCH2C CH3H3CCHHOCONHH2C CH2COHNOPOOOHOHCH2ONNNNNH2POOOCoenzyme A(CoA-SH)CH2CH2SHPantothenic Acid(Vitamin B5)OCH2C CH3H3CCHHOCONHH2C CH2COHNO POOOHOHCH2ONNNNNH2POOOAcetyl Coenzyme A(Acetyl-CoA)CH2CH2SCOCH3 Biotin OHNHHNSHHHOONNHHNSHHHOOHLys-EnzymeBiotinCarboxylaseprosthetic groupCarboxybiotinOCNONNHSHHHOOHLys-EnzymeFolic Acid HNNNNHNROHNNNNHNH2NORHHHHNNNNHNH2NORHHHHHNADPNADPHFolic Acid DihydrofolateTetrahydrofolate(THF)DihydrofolatereductaseHNNNNHNOHNOOOOH2NOFolic Acidp-AminobenzoicacidGlutamateN5N10NADPNADPHDihydrofolatereductase Cobalamin (Vitamin B12) COPOOOOHONNHONNO NH2NH2ONH2ONNH2NOONH2OHNCo3+ONH2NCyanocobalamin(Vitamin B12)Methylcobalamin 5´-DeoxyadenosylcobalaminCH3OPOOOOHONNHONNO NH2NH2ONH2ONNH2NOONH2OHNCo3+ONH2NNNNNH2HOOHOCH2OPOOOOHONNHONNO NH2NH2ONH2ONNH2NOONH2OHNCo3+ONH2Vitamin B6 NHOCH3HCHOPOOOOPyridoxal phosphateNHOCH3HCHOHOPyridoxalNHOCH3HCH2OHHOPyridoxineNHOCH3HCH2OHH2NPyridoxamineNHOCH3HCHOPOOONPyridoxal phosphateSchiff base to !-amino acidROO RC ORH2N RRCRN R+H2O+AldehydeorketoneAmine SchiffbaseAminotransferases O OOOO+O OH3NOOAspartateaminotransferase!-Ketoglutarate AspartateO OH3NOO+O OOOOGlutamate Oxaloacetate O OOOO+O OH3NAlanineaminotransferase!-Ketoglutarate AlanineO OH3NOO+O OOGlutamate Pyruvate NHOHCHNOEnzymeHPOOORCNH2HOOHNHOHCHNOEnzymeHPOOORCNHHOOHNHOHCHOPOOORCNHHOOEnzymeNHOHCH2OPOOORCNHOONH2EnzymeNHOHCH2OPOOONH3NH2EnzymeRCOOOHydrolysis!-aminoacid!-ketoacidLoss of!-carbonprotonH3C H3C H3CH3CH3CNHOHCHOPOOORCNHOOEnzymeH3CNH2NH2HSerine Hydroxymethyl Transferase Tetrahydrofolate(THF)O OCH2H3NOH+SerineSerinehydroxymethyltransferaseO OH3N+GlycineN5,N10-MethyleneTetrahydrofolateHNNNHHNHNH2NOp-aminobenzamide-glutamateTetrahydrofolate(THF)HNNNHNNH2NOp-aminobenzamide-glutamateH2C NHOHCHNOEnzymeHPOOOCH2CNH2HOOHNHOHCHNOEnzymeHPOOOCH2CNHHOOHNHOHCHOPOOOCH2CNHHOOEnzymeSerineLoss ofR-groupH3C H3C H3COHOHNH2OHNHOHCH2OPOOOCNHOOEnzymeH3CNH2HN5,N10MethyleneTHFNHOHCHOPOOOHCNHHOOEnzymeH3CNH2NHOHCHNOEnzymeHPOOOHCNH3HOOGlycineH3CProtonationof !-carbonProductdissociation(Schiff baseexchange)Vitamin K OOOOOOMenadione(Vitamin K3)Phylloquinone(Vitamin K1)Menaquinone-7(Vitamin K2) OOROHOHROOROOHNCOO OOOHNOOCO2 + O2!-glutamylcarboxylaseVitamin KepoxidereductaseVitamin KepoxidereductaseOOOHOWarfarin(Wisconsin AlumniResearch