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27 Cards in this Set

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Where is Zinc found in the body?

Highest concentration in bone, prostate, skin, retina


Content in body 1.5- 2.5 g



Sources in food

Protein-rich diets tend to be high in Zn

Red meats, seafood, poultry, pork, dairy (high in protein foods)


Americans get ~70% of dietary zinc from animal sources


Whole grains, vegetables (less absorption due tophytates)

Factors that decrease absorption

Phytic acid

Oxalic acid


Divalent minerals (Calcium, iron) may reduce absorption


Polyphenols (in tea and coffee)

Digestion

Normally bound to PRO so needs to be hydrolyzed



Absorption

Passive diffusion & carrier-mediated transport

Carrier-mediated: Predominant: Zip4 transporter


Divalent mineral transporter 1 (DMT1)


Bind to AA-- Amino acid transporters?


Paracellular diffusion


When Zn intake exceed capacity of Zip4


Absorption varies generally from 10-60%


Increases with low intake and decreases with high intake


Helps maintain Zn homeostasis in the body

Enterocyte zinc use

Used functionally or stored bound to proteins


Metallothioenine- short-term Zn storage


Main zn storage protin


Transported across basolateral membrane into plasma (Zinc transporters ZnT)

How is Zinc transported in the blood

Transport in blood

Bound to albumin (primary, ~60%)


macroglobulin and IgG


Amino Acids– histidine and cysteine

Where is zinc taken after blood transport

To liver

Uptake of Zinc

ZIPs and ZnTs facilitate Zn uptake and release butunclear (many of these transporters throughout thebody)

How Zinc regulates Metallothionein

Serves to store Zn but also may transport it toenzymes

Also exhibits antioxidant-type function =With stress synthesis increased, helps control free radical concentrations (acute phase response) Zinc can be released from metallothionein bylysosomal proteases

Metallothionein

Zinc regulates the gene expression of thioneinby binding metal regulatory elements (MREs)found in the promotor region of thionein gene ¨

A Zn-dependent metal transcription factor(MTF) binds promotor region to inducesynthesis


Thus zinc directly regulates production to trapzinc


Will trap other minerals too, esp copper (highzinc may induce a copper deficiency)

Zinc Function

Catalytic role

Structural role


Regulatory role

Catalytic role of Zinc

metalloenzymes

>300 known Zn-dependent enzymes


DNA/RNA polymerase


Enzymes involved in fatty acid, carbohydrate andprotein metabolism

Structural roll of Zinc

Stabilizes proteins and membrane structure

Regulatory role of Zinc

Control gene transcription, stabilizes transcription factors to bind DNA = zinc fingers

Zinc Fingers

Many transcription factors contain zinc

Conformational change so that it resembles a “finger” when bound to zinc


Interact with metal response elements (MREs)


Nearly 2000 zinc-dependent transcription factors identified

Immune Defense

Thymulin= Zn-dependent hormone peptide Binds T-cells and promotes differentiation andfunction

Zn deficiency decreases thymulin= T-cellnumbers and function


May increase susceptibility to illness


Antioxidant function

Protects from oxidation: Used in sunscreens, prevents oxidation of metal (rust)

Cu-Zn SOD


Stabilizes proteins and lipids by keeping them in reduced state


Metallothionein : Scavenges free radicals with cysteine

Other Zinc roles

Enzymes for heme synthesis

Collagen synthesis (wound repair)


Alcohol detoxification


Metabolism of vitamin A (retinol binding proteins)


Hormone release (insulin)

Interaction with Vitamin A

(formation of retinaldehyde from retinol– Zn-dependent dehydrogenase, Znalso needed for synthesis of retinol bindingprotein for retinol mobilization)

Interaction with Copper

Copper– Zn adversely affects copper absorption attributed to zincs stimulation ofmetallothionein which has a higher affinityfor copper than zinc

Increased concentrations of metallothionein bind and “trap” copper in the enterocyte


Risk of copper deficiency set the UL for zincat 40 mg/day

Excretion of Zinc

Mostly through GI tract-- feces

Sloughing of intestinal cells, pancreatic secretions


Small amount in urine


skin exfoliation/sweat

RDA

Men 11 mg


women 8 mg

Deficiency

Impaired growth and development

Skin lesions


Night blindness


Impaired reproduction


Delayed wound healing


Impaired immune function

Those at risk for deficiency

Elderly, decreased absorption/eat less meat

Vegetarians– may need 50% more in diet due to high phytates


Needs increased by alcoholism, chronic illness,stress, trauama, surgery, malabsorption

how is zinc toxic

relatively nontoxic

UL = 40 mg


Toxicity associated with zinc’s influence on copper

Assessment of zinc

Zinc in RBCs, leukocytes, neutrophils, plasma/ serum

Metallothionein concentrations


Urinary or hair zinc


Activity of zinc-dependent enzymes


But really there is no robust, sensitive marker for Zn Why? ú Homeostatic mechanisms, Non-specific deficiency symptoms