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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