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HistoryHistory
1509, recognized as element1509, recognized as element Essentiality demonstratedEssentiality demonstrated
Plants: 1869Plants: 1869 Animals: 1934Animals: 1934
DeficiencyDeficiency Considered unlikely until 1955 Considered unlikely until 1955
swine parakeratosis shown to be caused by Zn swine parakeratosis shown to be caused by Zn deficiencydeficiency
conditioned human deficiency demonstrated in 1956conditioned human deficiency demonstrated in 1956 1961, hypogonadal dwarfism suggested to be zinc 1961, hypogonadal dwarfism suggested to be zinc
deficiencydeficiency
FactsFacts
30th element in the periodic table (IIB 30th element in the periodic table (IIB element)element) MW = 65.37, completely filled d orbitalsMW = 65.37, completely filled d orbitals
In aqueous solutionsIn aqueous solutions One oxidation state, namely ZnOne oxidation state, namely Zn2+2+ Prefers tetrahedral complex formationPrefers tetrahedral complex formation
Not a redox active metalNot a redox active metal readily complexes with amino acids, readily complexes with amino acids,
peptides, proteins and nucleotidespeptides, proteins and nucleotides affinity for thiols, hydroxy groups & ligands affinity for thiols, hydroxy groups & ligands
with electron-rich nitrogen donorswith electron-rich nitrogen donors
DistributionDistribution Whole body: Whole body: 1.5g (female)-2.5g (male)1.5g (female)-2.5g (male)
Skeletal MuscleSkeletal Muscle 57% 57% BoneBone 29% 29% SkinSkin 6% 6% LiverLiver 5% 5% BrainBrain 1.5% 1.5% KidneysKidneys 0.7% 0.7% HeartHeart 0.4% 0.4% HairHair ~0.1%~0.1% Blood PlasmaBlood Plasma ~0.1%~0.1%
SourcesSources Relatively abundant mineralRelatively abundant mineral
Good sources: shellfish, beef and other red Good sources: shellfish, beef and other red meatsmeats
Slightly less good: Whole-grainsSlightly less good: Whole-grains most in bran and germ portionsmost in bran and germ portions 80% lost to milling80% lost to milling phytates, hexa & penta phosphates depress phytates, hexa & penta phosphates depress
absorptionabsorption P/Zn ratios of 10 or moreP/Zn ratios of 10 or more
Relatively good sources: nuts and legumesRelatively good sources: nuts and legumes Eggs, milk, poultry & fish diets lower than Eggs, milk, poultry & fish diets lower than
pork, beef, lamb dietspork, beef, lamb diets High meat diets enhance absorption High meat diets enhance absorption
280g or 10 oz fits right into food pyramid guide280g or 10 oz fits right into food pyramid guide cys & met form stable chelate complexescys & met form stable chelate complexes
Effect of trace mineral Effect of trace mineral source on animal source on animal
performanceperformance
Whole Body Whole Body FluxesFluxesPlasma/
Serum 2.4 mga-2
macroglobulin (30%) albumin
(60%)
Target tissuesIncluding
Liver1.2 g
Urine: 0.4-0.6 mg/da
Other Losses: Sweat, Skin, Hair up to 1 mg/da
Milk: 2-3 ug/mL
Seminal Fluid: 196 ug/mL
IntestineZn++ (50-100mM)
1-2 mg/daMetallothionineChelating Agents
Phytates
Diet Zn++
4-15 mg/da(~0.15 mM)
Pancreatic & Biliary
Excretion: 4-5 mg/da
Feces: 3-14 mg/da
Menstrual Loss: 0.1-0.5 mg
Dietary Factors that Dietary Factors that Affect Zn AbsorptionAffect Zn Absorption
Feed/Food sourceFeed/Food source Phytate (calcium-Phytate (calcium-
phytate-zinc phytate-zinc complex)complex) Mainly hexa- and Mainly hexa- and
pentaphosphate pentaphosphate derivativesderivatives
Highly dependent Highly dependent on calciumon calcium
Amino AcidsAmino Acids histidine, cysteinehistidine, cysteine
Presence/Absence of Presence/Absence of other divalent cationsother divalent cations Fe, CaFe, Ca
Efficiency of Efficiency of absorption can vary absorption can vary from 15-60%from 15-60% Under normal Under normal
conditions 1/3 of conditions 1/3 of dietary Zn is absorbeddietary Zn is absorbed
Zn status alters Zn status alters efficiency of efficiency of absorptionabsorption
Uptake and retention Uptake and retention is > in growing is > in growing animalsanimals
OverviewOverview Approximately 300 enzymes are associated with Approximately 300 enzymes are associated with
zinczinc Biological functions of Zn are divided into three Biological functions of Zn are divided into three
categoriescategories Catalytic, Structural, Regulatory Catalytic, Structural, Regulatory
Role in metabolismRole in metabolism Protein synthesisProtein synthesis Nucleic acid metabolismNucleic acid metabolism Carbohydrate and energy metabolismCarbohydrate and energy metabolism LipidLipid Epithelial tissue integrityEpithelial tissue integrity Cell repair and divisionCell repair and division Vitamin A and E transport and utilizationVitamin A and E transport and utilization Immune functionImmune function Reproductive hormonesReproductive hormones
AbsorptionAbsorption
Absorption takes place throughout the Absorption takes place throughout the intestineintestine GlycocalyxGlycocalyx
Barrier? Storage site?Barrier? Storage site? Primarily in the jejunumPrimarily in the jejunum Some absorption in the rumenSome absorption in the rumen No measurable amounts absorbed from No measurable amounts absorbed from
stomach cecum or colonstomach cecum or colon
AbsorptionAbsorption In small intestineIn small intestine
Nonmediated (nonsaturable) processNonmediated (nonsaturable) process Not affected by dietary Zn intake Not affected by dietary Zn intake
Mediated (saturable) processMediated (saturable) process Stimulated by Zn depletionStimulated by Zn depletion
AbsorptioAbsorptionn
Mucosa Serosa
Zn++ Zn++
NSBP
MTI
MTI-Zn
CRIP
CRIP-Zn
Zn++ Zn++
Zn++-Albumin
Albumin
CRIP=cysteine-rich intestinal protein; MTI=metallothionine; NSBP, non-specfic binding protein
Non-saturable = Passive Diffusion
Saturable =Bound to
form transportligand Zn++-Albumin
Transport in bloodTransport in blood Plasma contains approx .1% of the total zinc of the bodyPlasma contains approx .1% of the total zinc of the body Albumin is major portal carrierAlbumin is major portal carrier
Binds to albumin by tetrahedral ligation to sulfur atomsBinds to albumin by tetrahedral ligation to sulfur atoms 70% of Zn is bound to albumin in plasma70% of Zn is bound to albumin in plasma 20-30% bound to 20-30% bound to αα-2 macroglobulin-2 macroglobulin Other plasma proteinsOther plasma proteins
Transferrin, histidine-rich glycoprotein, metallothionineTransferrin, histidine-rich glycoprotein, metallothionine Plasma Zn concn’s respond to external stimuliPlasma Zn concn’s respond to external stimuli
Intake fluctuationsIntake fluctuations FastingFasting Acute stressesAcute stresses
infectioninfection Plasma Zn levels do not influence absorption from Plasma Zn levels do not influence absorption from
mucosamucosa Most reductions in plasma levels reflect increased Most reductions in plasma levels reflect increased
hepatic uptakehepatic uptake Hormonal controlHormonal control
TransportTransport Rapidly cleared from plasma by Rapidly cleared from plasma by
liverliver Fast component of 2 pool model (TFast component of 2 pool model (T1/21/2
= 12.3 da)= 12.3 da) Single dose of zinc is taken up with TSingle dose of zinc is taken up with T1/21/2 = =
20 s 20 s Slow component, other tissues (TSlow component, other tissues (T1/21/2 = =
300 da)300 da) Bone and CNS uptake slow Bone and CNS uptake slow Pancreas, liver and kidney most rapidPancreas, liver and kidney most rapid RBC & muscle in betweenRBC & muscle in between Exchangeable pool & zinc statusExchangeable pool & zinc status
Cellular UptakeCellular Uptake
Hepatic uptake via a biphasic processHepatic uptake via a biphasic process Contribution to overall Zn fluxContribution to overall Zn flux
Sequesters newly absorbed ZnSequesters newly absorbed Zn Removes Zn from the circulationRemoves Zn from the circulation
Saturable process – initial stepSaturable process – initial step Temperature dependentTemperature dependent rapidrapid Stimulated by glucocorticoidsStimulated by glucocorticoids
Linear accumulation – subsequent stepLinear accumulation – subsequent step slowslow Not affected by dietary Zn intakeNot affected by dietary Zn intake
Does not require energyDoes not require energy
Cellular UptakeCellular Uptake ErythrocytesErythrocytes
Depends upon bicarbonate ionsDepends upon bicarbonate ions Fibroblasts, proximal tubule, Fibroblasts, proximal tubule,
lymphocytelymphocyte Biphasic uptake (same as liver)Biphasic uptake (same as liver)
Intracellular TransportIntracellular Transport
Zinc transporters regulate Zn ion Zinc transporters regulate Zn ion concentrations through import, concentrations through import, export or sequestering Zn into export or sequestering Zn into vesiclesvesicles Storage, toxicityStorage, toxicity
2 families exist: 2 families exist: ZnT- mainly exports Zn ions from cells ZnT- mainly exports Zn ions from cells ZIP – important for Zn influxZIP – important for Zn influx
Intracellular Intracellular TransportTransport
Number of transportersNumber of transporters ZnT-1: all organs, small intestine ZnT-1: all organs, small intestine
(basolateral membrane), kidney (basolateral membrane), kidney (tubular cells), placenta (tubular cells), placenta EffluxEfflux
ZnT-2: intestine, kidney, testisZnT-2: intestine, kidney, testis Efflux & (?) intracellular vesiclesEfflux & (?) intracellular vesicles
ZnT-3: brain (synaptic vesicles) & ZnT-3: brain (synaptic vesicles) & testistestis Influx, intracellular retentionInflux, intracellular retention
ZnT-4: mammary gland & brainZnT-4: mammary gland & brain Efflux (into milk)Efflux (into milk)
Lethal mouse transgenicLethal mouse transgenic
Intracellular TransportIntracellular Transport
ZIP family transporters:ZIP family transporters: Consist of: Consist of:
hZIP1hZIP1 hZIP2hZIP2 hZIP3hZIP3
Responsible for influx of Zn as well as Responsible for influx of Zn as well as MnMn2+2+, Cd, Cd2+2+, and other divalent cations , and other divalent cations into cellsinto cells
Intracellular Intracellular TransportTransport
Number of transportersNumber of transporters DCT1: duodenum, jejunum, kidney, DCT1: duodenum, jejunum, kidney,
bone marrow, othersbone marrow, others Non-specific: Zn, Cd, Mn & Cu actually Non-specific: Zn, Cd, Mn & Cu actually
have slightly higher affinity than Fe, the have slightly higher affinity than Fe, the mineral for which the transport actions mineral for which the transport actions of this protein was first identified.of this protein was first identified.
Competition between Fe & Zn & CuCompetition between Fe & Zn & Cu
StorageStorage Storage sitesStorage sites
No specfic storage sites are recognizedNo specfic storage sites are recognized Within cells, amounts sequestered within Within cells, amounts sequestered within
metallothionine could be considered as storesmetallothionine could be considered as stores Anorexia, muscle catabolism, tissue zinc Anorexia, muscle catabolism, tissue zinc
releaserelease Metalloenzymes cling tenaciously to zincMetalloenzymes cling tenaciously to zinc
Serum/plasma zinc drops rapidly (~1 Serum/plasma zinc drops rapidly (~1 week) with zinc deficient dietweek) with zinc deficient diet Zinc turnover is extensive and rapidZinc turnover is extensive and rapid
Two-components of turnover, fast ~12.3 days, and Two-components of turnover, fast ~12.3 days, and slow, ~300 daysslow, ~300 days
Fast pool is also called the “exchangeable” Fast pool is also called the “exchangeable” poolpool
Usually amounts to 157-183 mg ZnUsually amounts to 157-183 mg Zn
ExcretionExcretion Lost via hair, sweat, desquamation, bile Lost via hair, sweat, desquamation, bile
pancreatic secretions, seminal fluid, urine, pancreatic secretions, seminal fluid, urine, fecesfeces
Main endogenous lossMain endogenous loss Secretions into gutSecretions into gut
Bile and pancreasBile and pancreas Mucosal cellsMucosal cells
Urinary and integumental lossesUrinary and integumental losses < 20% under normal conditions< 20% under normal conditions
Losses increase with trauma, muscle catabolism, and Losses increase with trauma, muscle catabolism, and administration of chelating agents (EDTA) administration of chelating agents (EDTA)
Primarily in fecal materialPrimarily in fecal material Unabsorbed ZnUnabsorbed Zn Secreted Zn (endogenous sources)Secreted Zn (endogenous sources)
From pancreatic and intestinal sourcesFrom pancreatic and intestinal sources
RegulationRegulation MetallothioneinMetallothionein
Concentrated in liver, kidney, pancreas, intestineConcentrated in liver, kidney, pancreas, intestine Acts as a ZnActs as a Zn2+2+ buffer buffer
Controls free ZnControls free Zn2+2+ level level Control intracellular Zn pool responsive to both hormones and dietControl intracellular Zn pool responsive to both hormones and diet
Zn-binding protein, metallothionein (MT), is involved Zn-binding protein, metallothionein (MT), is involved in the regulation of Zn metabolismin the regulation of Zn metabolism
MT is inducible by dietary Zn via the metal response MT is inducible by dietary Zn via the metal response element (MRE) and MTF-1 mechanism of element (MRE) and MTF-1 mechanism of transcriptional regulationtranscriptional regulation ↑↑ in cellular MT in cellular MT ↑↑ Zn binding within cells Zn binding within cells
Acute infections associated with proinflammatory Acute infections associated with proinflammatory cytokines increses Zn uptake into liver, bone marrow cytokines increses Zn uptake into liver, bone marrow and thymus and reduces the amount going to bone, and thymus and reduces the amount going to bone, skin and intestineskin and intestine
Metabolic InteractionsMetabolic Interactions
Interactions of other divalent cations Interactions of other divalent cations in the intestinal lumenin the intestinal lumen Fe, Fe, SnSn, , CdCd → ↓ Zn → ↓ Zn ↑ ↑ Zn → ↓ CuZn → ↓ Cu
InteractionsInteractions CopperCopper
High Zn diets reduce Cu absorption High Zn diets reduce Cu absorption electronic configuration competitionelectronic configuration competition
Metallothionine synthesis inducedMetallothionine synthesis induced sequesters Cu in mucosal cell preventing sequesters Cu in mucosal cell preventing
serosal transferserosal transfer Happens with 150mg Zn for two yearsHappens with 150mg Zn for two years Can be used with Wilson’s disease patientsCan be used with Wilson’s disease patients High copper diets do not interfere with Zinc High copper diets do not interfere with Zinc
absorptionabsorption IronIron
Supplements inhibit zinc absorptionSupplements inhibit zinc absorption Ferrous > Ferric, heme no effectFerrous > Ferric, heme no effect Pregnant and taking >60mg Fe/day should Pregnant and taking >60mg Fe/day should
also take Znalso take Zn
InteractionsInteractions CalciumCalcium
High Ca diets reduce Zn absorption High Ca diets reduce Zn absorption effect enhanced in phytate rich dietseffect enhanced in phytate rich diets not sure how much of a problem in humansnot sure how much of a problem in humans
post menopausal women yes, adolescent girls, nopost menopausal women yes, adolescent girls, no OtherOther
Tin (Sb), not usually high in diet, but diets Tin (Sb), not usually high in diet, but diets high in Tin can increase fecal Zn excretionhigh in Tin can increase fecal Zn excretion
Cadmium (Cd), alter Zn distribution in Cadmium (Cd), alter Zn distribution in body rather than altering absorptionbody rather than altering absorption
Folic acid, conjugase requires ZnFolic acid, conjugase requires Zn High doses sometimes impair Zn status further High doses sometimes impair Zn status further
in low Zn situation - mechanism currently in low Zn situation - mechanism currently unclearunclear
FunctionFunction Zinc-containing enzymesZinc-containing enzymes
More than 70 enzymesMore than 70 enzymes Secondary & tertiary protein structuresSecondary & tertiary protein structures
Metal stabilized active sitesMetal stabilized active sites
Examples of general typesExamples of general types dehydrogenasesdehydrogenases phosphatasesphosphatases peptidasespeptidases kinaseskinases deaminasesdeaminases
InsulinInsulin
FunctionFunction
Cu/Zn Superoxide DismutaseCu/Zn Superoxide Dismutase General class of enzymes that protect General class of enzymes that protect
against oxidative damage in the body.against oxidative damage in the body. InsulinInsulin
Zn important structurallyZn important structurally Zn needed for insulin “stored” in Zn needed for insulin “stored” in
pancreaspancreas Functionality drops rapidly so more of a Functionality drops rapidly so more of a
“working store” than a static store“working store” than a static store
FunctionFunction
Nuclear transcription factors (>130)Nuclear transcription factors (>130) Same protein structural role forms “zinc-Same protein structural role forms “zinc-
fingers”fingers” ““Zn-fingers” bind DNAZn-fingers” bind DNA
allow different nuclear hormones to interact with allow different nuclear hormones to interact with DNA via different DNA binding proteinsDNA via different DNA binding proteins
up to 37 “fingers” have been found on a single up to 37 “fingers” have been found on a single transcription factortranscription factor
Vit. A, Vit. D, steroid hormones, insulin-like growth Vit. A, Vit. D, steroid hormones, insulin-like growth factor-1, growth hormone, and others bind to zinc-finger factor-1, growth hormone, and others bind to zinc-finger proteins to modulate gene expressionproteins to modulate gene expression
Zn is responsible for thymidine incorporationZn is responsible for thymidine incorporation
FunctionFunction
Cell DifferentiationCell Differentiation Thymidine kinase activityThymidine kinase activity Creatine kinase activityCreatine kinase activity
Transcription FactorsTranscription Factors
Transcription factorsTranscription factors Regulate gene expressionRegulate gene expression Involved in virtually all biological processes: Involved in virtually all biological processes:
Development, differentiation, cell proliferation, Development, differentiation, cell proliferation, response to external stimuliresponse to external stimuli
Consists of 2 domainsConsists of 2 domains DNA Binding Domain (DBD) – recognizes and DNA Binding Domain (DBD) – recognizes and
binds to specific DNA sequence elements in the binds to specific DNA sequence elements in the promoter of target genespromoter of target genes
Protein-interacting Transactivation Domain (TAD) Protein-interacting Transactivation Domain (TAD) – influences the rate of transcription– influences the rate of transcription
Zinc Finger ProteinsZinc Finger Proteins Zinc finger proteins are characterized by Zinc finger proteins are characterized by
their utilization of zinc ions as structural their utilization of zinc ions as structural componentscomponents
C2H2 zinc finger binding motifC2H2 zinc finger binding motif Predominant motif in eukaryotic transcription Predominant motif in eukaryotic transcription Involved in skeletal differentiationInvolved in skeletal differentiation Zinc binding motif is determined by the presence Zinc binding motif is determined by the presence
of 2 cysteine and 2 histidine residues that engage of 2 cysteine and 2 histidine residues that engage in a four coordinate bond with a singe Zn ionin a four coordinate bond with a singe Zn ion
Bind to response elements in the upstream Bind to response elements in the upstream promoters of genes transcribed by RNA poly 2promoters of genes transcribed by RNA poly 2
Binds to 5S ribosomal RNA gene, and 5S RNA, Binds to 5S ribosomal RNA gene, and 5S RNA, and activates transcription by RNA polymerase 3.and activates transcription by RNA polymerase 3.
FunctionFunction
Zinc FingersZinc Fingers Mutation c/ablation of bindingMutation c/ablation of binding
in case of Zif268, loss in sequence-specific in case of Zif268, loss in sequence-specific DNA binding that allowed viral infectionDNA binding that allowed viral infection
Iron can replace Zn in “fingers”Iron can replace Zn in “fingers” Low Zn and high FeLow Zn and high Fe Fe gives rise to ROS more readilyFe gives rise to ROS more readily
DNA damage & carcinogenesis?DNA damage & carcinogenesis?
Cadmium can replace Zn in “fingers”Cadmium can replace Zn in “fingers” Non-functional, cytotoxicNon-functional, cytotoxic
Transcription FactorsTranscription Factors RevelationRevelation
Gene expression is controlled by specific Gene expression is controlled by specific proteins call transcription factorsproteins call transcription factors
Zinc containing transcription factors Zinc containing transcription factors account for 1% of genomeaccount for 1% of genome
Zinc plays key structural role in Zinc plays key structural role in transcription factor proteinstranscription factor proteins
Ligands for transcription factors Ligands for transcription factors include:include:
Vitamin AVitamin A Vitamin DVitamin D Bile acidsBile acids Thyroid hormonesThyroid hormones
Membrane StabilityMembrane Stability
Membrane fractions contain high Membrane fractions contain high concentrations of Znconcentrations of Zn Increases rigidity of cellIncreases rigidity of cell
Protection from oxidative damageProtection from oxidative damage Competition for binding sites with redox Competition for binding sites with redox
metalsmetals
Membrane FunctionMembrane Function
In deficient animals:In deficient animals: Failure of platelet aggregationFailure of platelet aggregation
Due to impaired Calcium uptakeDue to impaired Calcium uptake Peripheral neuropathyPeripheral neuropathy
Brain synaptic vesicles exhibit impaired Brain synaptic vesicles exhibit impaired calcium uptakecalcium uptake
Increased osmotic fragility in RBCsIncreased osmotic fragility in RBCs Decreased plasma membrane sulfhydryl Decreased plasma membrane sulfhydryl
concentrationconcentration
Immune FunctionImmune Function
After Zinc depletionAfter Zinc depletion All functions within monocytes were All functions within monocytes were
impairedimpaired Cytotoxicity decreased in Natural Killer CellsCytotoxicity decreased in Natural Killer Cells Phagocytosis is reduced in neutrophilsPhagocytosis is reduced in neutrophils Normal function of T-cells are impairedNormal function of T-cells are impaired B cells undergo apoptosis B cells undergo apoptosis
High Zn supplementation shows High Zn supplementation shows alterations in cells similar to Zn alterations in cells similar to Zn depletiondepletion
Vitamin A & Vitamin A & ZincZinc
Zn influences Vitamin A metabolismZn influences Vitamin A metabolism Absorption, transport, and utilizationAbsorption, transport, and utilization
Vitamin A transport is mediated through protein Vitamin A transport is mediated through protein synthesissynthesis
Zn deficiency can depress synthesis of retinol-binding Zn deficiency can depress synthesis of retinol-binding protein in liverprotein in liver
Oxidative conversion of retinol to retinal requires Zn-Oxidative conversion of retinol to retinal requires Zn-dependent retinol dehydrogenase enzymedependent retinol dehydrogenase enzyme
Retinol to retinaldehyde (retinal), for visual processesRetinol to retinaldehyde (retinal), for visual processes Night BlindnessNight Blindness
Hallmark deficiency sign for Vitamin AHallmark deficiency sign for Vitamin A Seen with Zn deficiency as well, why?Seen with Zn deficiency as well, why?
Stojanovic, Stitham and Hwa: Critical Stojanovic, Stitham and Hwa: Critical Rose of Transmembrane segment Zn Rose of Transmembrane segment Zn binding I the structure and function of binding I the structure and function of rhodopsin JBC 279(34):35932-35941, 2004rhodopsin JBC 279(34):35932-35941, 2004 Rhodopsin proteins Rhodopsin proteins
Vitamin AVitamin A
trans-Retinal + opsin
trans-Retinol
11-cis-Retinal
11-cis-Retinol
[11-cis-Retinal]Rhodopsin
Spontaneous i
n dark
+ opsin Light
Retinol isomeraseworks on vitamin A
bound to CRBP
Retinol isomerase
Alcohol dehydrogenase NADH (NADPH)NAD+ (NADP+)
Blood +Epithelium
“bleaching”
Zn-dependentProtein folding
Mechanisms of ToxicityMechanisms of Toxicity Excess accumulation within cells may disrupt Excess accumulation within cells may disrupt
functions of biological moleculesfunctions of biological molecules Protein, enzymes, DNAProtein, enzymes, DNA
Leads to toxic consequencesLeads to toxic consequences AnemiaAnemia
Impaired copper availabilityImpaired copper availability Acute excessive intakesAcute excessive intakes
Local irritant to tissues and membranesLocal irritant to tissues and membranes GI distress, nausea, vomiting, abdominal cramps, GI distress, nausea, vomiting, abdominal cramps,
diarrheadiarrhea Relatively non-toxicRelatively non-toxic
Sources of exposure – drinking water, feed, Sources of exposure – drinking water, feed, polluted airpolluted air
DeficiencyDeficiency SignsSigns
Growth retardationGrowth retardation Delayed sexual maturation Delayed sexual maturation
& impotence& impotence Impaired testicular Impaired testicular
developmentdevelopment Hypogonadism & Hypogonadism &
hypospermiahypospermia AlopeciaAlopecia Acroorifical skin lesionsAcroorifical skin lesions
Other, glossitis, alopecia & Other, glossitis, alopecia & nail dystrophynail dystrophy
Immune deficienciesImmune deficiencies Behavioral changesBehavioral changes
More signsMore signs Night blindness Night blindness Impaired taste Impaired taste
(hypoguesia)(hypoguesia) Delayed healing of Delayed healing of
wounds, burns, wounds, burns, decubitus ulcersdecubitus ulcers
Impaired appetite & Impaired appetite & food intakefood intake
Eye lesions including Eye lesions including photophobia & lack of photophobia & lack of dark adaptationdark adaptation
DeficiencyDeficiency Monogastric more susceptibleMonogastric more susceptible
Chickens & pigs used to become deficient Chickens & pigs used to become deficient with high corn dietswith high corn diets Old enemy phytateOld enemy phytate
Ruminants resistant due to ability to break Ruminants resistant due to ability to break down phytatesdown phytates
DiabetesDiabetes Increases urinary zinc excretion Increases urinary zinc excretion
Can cause deficiencyCan cause deficiency ElderlyElderly
Poor intakes & altered physiologyPoor intakes & altered physiology
Deficiency During Deficiency During PregnancyPregnancy
Zn deficient rats failed to conceiveZn deficient rats failed to conceive Abnormalities of blastocyst developmentAbnormalities of blastocyst development Offspring had high incidence of Offspring had high incidence of
abnormalitiesabnormalities Deformities of brain, skull, limbs, eyes, heart, Deformities of brain, skull, limbs, eyes, heart,
lungslungs Low Zn intake during the third trimester Low Zn intake during the third trimester
may not have such profound effectsmay not have such profound effects Main stages of differentiation are already Main stages of differentiation are already
completecomplete Can result in low birth weight, and prolonged Can result in low birth weight, and prolonged
and difficult parturitionand difficult parturition
Deficiency During Deficiency During PregnancyPregnancy
ZincAdequate
ZincDeficient
3 days 4 days
From Hurley&Schrader, 1975
DeficiencyDeficiencyMalformations in Zn deficiencyCleft lipCleft palateBrain (Hydrocephalus, anencephalus or exencephalus)Micro- or agnathiaMicro- or anopthalmiaClubbed feetA- or syndactylyCurly or stubby tailDorsal herniationHeart (abnormal position)
Lung (missing lobes)
Urogentital (Hydronephrosis, missing kidney, or abnormal positions)
Stress ResponseStress Response Factors that decrease plasma Zn Factors that decrease plasma Zn
concentrationconcentration Infection Infection Bacterial endotoxinsBacterial endotoxins SurgerySurgery BurnsBurns PregnancyPregnancy
IL-1 causes increased Zn uptake by liver IL-1 causes increased Zn uptake by liver thymus and bone marrowthymus and bone marrow
Severe trauma or death can result from Severe trauma or death can result from Zn supplementation to stressed animalsZn supplementation to stressed animals
2002 DRI’s2002 DRI’s
InfantsInfants UL=(x)UL=(x) 0-6 mo: 2 mg/d0-6 mo: 2 mg/d AI AI (4)(4)
Children & adolescentsChildren & adolescents 7mos-1 yr: 3 mg/d 7mos-1 yr: 3 mg/d (5)(5) 1-3 yrs: 3 mg/d 1-3 yrs: 3 mg/d (7)(7) 4-8 yrs: 5 mg/d 4-8 yrs: 5 mg/d (12)(12) 9-13 yrs: 8 mg/d9-13 yrs: 8 mg/d (23)(23) 14-18 yrs: 14-18 yrs: (34)(34)
MalesMales 11 mg/da11 mg/da Females 9 mg/daFemales 9 mg/da
Adults: 19 yrs & older (40)
Men: 11 mg/daWomen: 8 mg/da
Pregnancy: 11-18 yrs: 12 mg/da (34)19-50 yrs: 11 mg/day (40)Lactation: 11-18 yrs: 13mg/da (34)19-50 yrs: 12 mg/day (40)
FootnoteMales need more than females due to high Zn content of seminal fluids & relatively low Zn loss through menstruation