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Water Soluble Vitamins
Dr. NasimAP biochem
Definition and ClassificationNon-caloric organic nutrientsNeeded in very small amountsFacilitators help body processes proceed; digestion, absorption, metabolism, growth etc.Some appear in food as precursors or provitamins
Definition and Classification2 classes, Table 7.1Fat soluble:
Water soluble:
Water Soluble Vitamins: CharacteristicsEssential Organic StructureNon-energy ProducingMicronutrientsStability BioavailabilityToxicity
Fat vs. Water Soluble Vitamins
Characteristics Water SolubleFat SolubleAbsorptionDirectly to bloodLymph via CMTransportfreeRequire carrierStorageCirculate freelyIn cells with fatExcretionIn urineStored with fatToxicityPossible w supplementsLikely wsupplementsRequirementsEvery 2-3 daysEvery week
ThiaminStructurepyrimidine ringthiazole ringmethyl bridge
Thiamin : vitamin formThiamin pyrophosphate: coenzyme formPyrimidine ringThiazole ring
Chemical CharacteristicsVery labile nutrientHeatstable in crystalline formless stable in solutionAlkali - very unstable with heatbaking soda
Chemical CharacteristicsSulfites - decomposes B-1High cooking/processing lossesheat leaching
Absorption of B-1in duodenumactive transport (low thiamin levels)requires sodium and folic acidpassive transport (hi B-1 levels)
Absorption of B-1phosphorylation to active form inside cells (TPP)transported via portal bloodno significant storage, excess to urine
Biochemical Functions of B-1Oxidative Decarboxyation ReactionsPyruvate DehydrogenasePyr+CoA+NAD --> AcCoA+CO2 +NADHa-keto-glutarate dehydrogenaseaKG+CoA+NAD-->SuccCoA + CO2+NADHimportant in CHO/energy metabolism
Pyruvate + CoA + NAD+ ------> CO2 + acetyl-CoA + NADH + H+
Biochemical Functions of B-1TransketolationHMP pathwayPeripheral Nerve FunctionTPP or TPPPnon-cofactor functionmechanism?
Thiamin DeficiencyBeri-Berianorexia, fatigue, depressioneffects on cardiovascular systemnervous system
Infantile Beri-Berifirst 6 monthsbreast milk deficient in B-1mother w/o symptomsrapid onsetcyanosis, tachycardia, labored breathingheart failure and death
Wet Beri Berisymptoms similar to congestive heart failurePitting edema - trunk, limbs, facelabored breathing, tachycardiarapid deteriorationfatal cirulatory collapseresponds rapidly to B-1 supplements
Dry Beri-Berino edemaprogressive wastingnumbing and weakening of extremitieschronic infections
Assessment of Thiamin StatusUrinary thiamin excretionBlood or serum thiamin concentration[pyr + lac] in blooderythrocyte transketolase activitystimulation with B-1
2000 RDA for Thiamin
Males19-30yrsFemales19-30yrsRDA mg/d1.21.1EAR1.00.9NHANES IIIMean intake1.781.45
Fridays Quiz Read:RiboflavinVitamin B-6BiotinPantothenateKnowFunctionsCofactor and vitamin formsDeficiency and toxicity symptoms and causes
NiacinStructureNicotinic Acid = NiacinNicotinamide = Niacinamide
Cofactor Forms of NiacinNicotinamide Adenine DinucleotideNADnicotinamide-ribose-PP-ribose-adenineNicotinamide Adenine Dinucleotide PhosphateNADPnicotinamide-ribose-PP-(ribose-P)-adenine
Nicotinic Acid (Plant form)Nicotinamide (animal form)(reduced form)
Nicotinamide Adenine DinucleotidenicotinamideadenineIf Phosphate here ->NADP
Chemical Characteristics of Niacinrelatively stable tolightheatoxidationalkalimajor losses due to leaching
Digestion and Absorption of Dietary NiacinCoenzyme form in foodhydrolysis in small intestine to free vitaminabsorbed in duodenumnicotinic acid protein bound in cornrequires alkali treatment (lime) to release niacin
Metabolism of B-3conversion of free vitamin to coenzyme in all cellsno storageexcesses metabolized in liver to variety of chemicalsmetabolites excreted in urine
Synthesis of B-3from Tryptophanpathway requires B-6 (also B2)60 mg of TRY required to make 1 mg B-3corn is low in both B-3 and TRY
Biochemical Functions of B-3Oxidation-Reduction Reactions (NAD/NADHDehydrogenasesElectron Transport System
Involved in energy production
Pyruvate + CoA + NAD+ ------> CO2 + acetyl-CoA + NADH + H+
Biochemical Functions of B-3Synthetic Pathways (NADPH)FA synthesisCholesterol synthesisNEAA synthesisPurine & Pyrimidine synthesis
Deficiency of B-3Pellegra Dermatitisscaly dermatitis, sun exposedDementiaconfused, disorientedDiarrheairritation/inflammation of mucous membranes
Assessment of B-3 StatusUrinary excretion of niacin metabolitesN-methyl nicotinamide2-pyridone
2000 RDA for NiacinNiacin Equivalents (NE)1 NE = 1 mg B-3 = 60 mg TRY
Males19-30 yrsFemale19-30 yrsRDA (NE/d)1614EAR (NE/d)1211
Niacin Toxicity1-3g/day for treatment of hypercholesterolemiaincreases histamine releaseskin flushingincrease risk of peptic ulcersliver injurytime release forms greater risk of liver injury
Folic Acid / FolacinStructure pteridine ring - PABA - glutamateStabilityvery sensitive to heat easily oxidizedleached
Digestion & Absorptiondietary form: polyglutamyl folateglutamate gamma linkedFolate conjugaseZinc deficiencyalcoholismdrug interactionsfolate absorbed as monoglutamate (free folate)dietary supplement: free folate
Folate MetabolismIntestinal Cellsfolate reduced to tetrahydrofolatefolate reductaseinhibited by methotrexate (chemotheraputic drug)methylated to N5-methyl-THFprimary blood form
Folate FunctionsSingle carbon metabolism
Folate FunctionsInterconversion of serine and glycineser + THF gly + 5,10-Me-THFDegradation of histidinehis->->->formiminoglutamate(FIGLU)FIGLU+THF -> glu + 5-forminino-THFhistidine load testFunctional test for folate status
Folate FunctionsPurine and Pyrimidine SynthesisdUMP + 5,10-Me-THF -> dTMP + THFMethionine Synthesishomocysteine + 5-Me-THF -> MET + THFMET as a methyl donor for choline synthesis
Folate DeficiencyMegaloblastic Anemiadecreased DNA synthesisfailure of bone marrow cells to dividenormal protein synthesisresults in large immature RBCscontrast with microcytic hypochromic anemia
Folate DeficiencyHomocysteineCoronary Heart Disease risk factor ?genetic homocystinuria - premature CHDhi [homocys] related to hi CHD risklo [folate, B-12, B-6] related to hi CHD risklo intake of B-vit related to hi CHD risk
Folate and Neural Tube DefectsDefects in formation of neural tube (brain & spinal cord)First two months gestationAnencephalyabsence of cerebral hemispheres
Folate and Neural Tube DefectsSpina bifidadefective closure of vertebral columnspinal cord protrusion from spinal column results in damage to spinal cordlower limb and hip paralysisrectal and bladder problems
NTD PrevalenceUS: 4000 live births with NTDs/yr1/1000 pregnanciesWorld:400,000 live births with NTDs/yr
NTDs and FolateNTDs associated with mothers with low blood [folate]Estimated that 50% of NTDs prevented with folate supplementation w/ 200 ug/dDRI adults = 400 ug/dDRI prenancy = 600 ug/dtypical US intake = 280-300 ug/d
Folate and Grain EnrichmentJan 1, 1998140 ug/100g enriched grainresults in additional 100 ug/dmay reduce about 25% of NTDslimited because of masking of B-12 deficiency
Folate: 2000 DRIDietary Folate Equivalents (DFE)1 DFE = 1 ug food folate0.6 ug fortified food folate taken with food0.5 ug folate supplement on empty stomach
Folate DRI (2000)For women capable of becoming pregnant, it is recommended that they consume 400 ug of folate as supplements or fortified foods in addition to folate containing foods.
Males19-30 yrFemales19-30 yrRDA (ug/d)400400EAR (ug/d)320320UL (ug/d)10001000NHANES IIIMedian intake (prior to fortification)277223
Vitamin B-12Structurecobalaminemethyl cobalaminetransport and coenzyme formadenosyl cobalaminestorage and coenzyme form
Dietary SourcesAnimal products including milk and eggsGI microorganismsVegan sourcesN-fixing legumesfortified grainsvitamin supplements
Digestion & Absorption of B-12Protein bound in foodsreleased by acid and pepsinElderly at riskR-proteingastric secretionbinds with free B-12protects B-12 from bacterial use ?
Digestion & Absorption of B12Intrinsic Factorgastric glycoproteinbinds with B12 in small intestineIF-B12 complex binds to B12receptor in ileum for absorptionB12 absorption requires functioning stomach, pancreas, and ileum
Causes of B-12 DeficiencyInadequate intake - rareDRI adults 2.4 ug/dUsual intake 7-30 ug/dMalabsorption of B-12IF deficiencyother GI tract problems
Shilling Test for MalabsorptionSaturation of B12 by injectionOral administration of radiolabeled B12free B12IF-B12Measure urinary excretion of labeled B12
Functions of B12Homocysteine to Methioninemethionine synthetaserequires 5-methyl THFdeficiency of B12 results in methyl-trap of folateresults in megaloblastic anemiasynergistic effect of B12 and folate
Functions of B12Mutases methyl malonyl CoA mutaseproprionyl-CoA ->->succinyl-CoAaccumulation of methyl-malonate may inhibit AcetylCoA carboxylase
B-12 DeficiencyPernicious anemiamegaloblastic anemia Methyl-folate trap Delayed or failure of normal cell division due to impaired DNA synthesisneuropathy defective myelinationprogressive peripheral weakeningunresponsive to folateupper limit to folate supplementation/enrichment
Vitamin C - Ascorbic AcidStructureMetabolismoxidation/reductiondehydroascorbic aciddehydroascorbate reductaseglutathione (GSH) glutamate-cysteine-glycine
Functions of Vitamin CEnhances absorption of ironreduces iron to more absorbable ferrous formchelates with ferrous ion to make it more soluble
Functions of Vitamin CHydroxylation of proline and lysinepost-translational reaction of procollagenhydroxylated collagen can be cross-linked to triple helix collagenScurvy - weak collagen
Functions of Vitamin CHydroxylation ReactionsInvolves O2 and metal coenzyme(ferrous, cuprous)Carnitine synthesisTyrosine synthesis & catabolism
Functions of Vitamin CHydroxylation ReactionsSynthesis of NeurotransmittersDopamineNorepinephrineSerotoninBile acid synthesis
Functions of Vitamin CAntioxidant ActivityReacts and removes active oxygen speciesPro-oxidant ActivityReduces metals to their pro-oxidant forms
ScurvyBleeding gumspetechiaeeasy bruisingimpaired wound healing and bone repairjoint painanemia
RDA for Vitamin C10 mg/day prevents scurvyhistoric RDAs 45-70 mg (60mg in 1989), 75mg in 2000prevention of scurvy vs antioxidant effect with supplements?
Toxicity of Vitamin CUL adults: 2000mg/dOsmotic diarrheaOxalate kidney stonesDecreases uric acid reabsorption resulting in increased risk of goutAffects diagnostic tests in feces and goutfecal bloodurinary glucose
Variety is the Key Vitamins are derived from a variety of foods.
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