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Phar 722

Pharmacy Practice III

Trace Elements
-

Zinc


Spring 2006

Zinc Learning Objectives


Know the uptake, distribution and excretion of zinc.


Know the bioavailability of dietary zinc.


Know the biodistribution of zinc.


Know the biochemical functions of zinc.


Know the causes and symptoms of zinc deficiency.


Know the symptoms of zinc toxicity.


Know the current efficacy of zinc supplements in
certain diseases discussed in class.


List the common side effects of oral zinc therapy.


Know the RDAs for adults and ULs for children and
adults.


Zinc’s Three Biochemical Roles
-
1


Catalytic Role


Structural Role


Regulatory Role

Zinc’s Three Biochemical Roles
-
2


Catalytic Role


Over 100 specific zinc metalloenzymes depend on
zinc for catalytic activity including:


Alcohol dehydrogenase


Ribonucleic acid polymerases


Carbonic anhydrase


Alkaline phosphatase


Carboxypeptidase


Glutamic dehydrogenase


Lactic dehydrogenase


Mechanism


Zinc is a Lewis acid accepting electrons (different from
oxidation
-
reduction reactions)

Zinc’s Three Biochemical Roles
-
3


Structural Role


Coordinates with electron rich amino acid
side chains of proteins stabilizing tertiary
and quaternary structure.


Copper
-
zinc superoxide dismutase


Copper is the cofactor in the oxidation
-
reduction
reaction and zinc stabilizes tertiary structure.


Intracelluar binding of tyr kinase to T
-
cell receptors.


Coordination with cys and his residues
produces “zinc finger
-
like” structure.


Zinc fingers are important regulators of DNA
binding transcription factors.

Zinc’s Three Biochemical Roles
-
4


Regulatory Role


This function is poorly understood.
Examples include:


Regulator of gene expression possibly by
changes in binding to transcription factors.


Zinc transporter proteins


Metallothionein gene producing a metalloprotein that
regulates zinc trafficking.


Apoptosis


Protein kinase C activity


Cell signaling


Uptake, Utilization & Excretion
-
1


Dietary zinc is bound in metalloproteins (see
previous slides).


The digestive process frees it


It then becomes bound to endogenous proteins
found in the intestinal lumen.


There is active transport in the jejunum.


Zinc transport speeds up in states of zinc
depletion.


The human body contains about 2 gm zinc.


Over 85% of these 2 gm is in skeletal muscle and
bone.


0.1% of total zinc (10


15
μ
mol/L) in plasma.

Uptake, Utilization & Excretion
-
2


Zinc apparently uses the same
transport systems as other divalent
cations.


Iron supplements might lower the percent
of zinc absorbed.


Zinc supplements might lower the percent
of copper absorbed.


Zinc elimination is by secretion into the
intestine followed by excretion in the
feces.

Zinc Deficiency


Symptoms do not correlate with zinc’s biochemical
roles.


Depressed growth


Delayed sexual maturation


Immune dysfunction


Diarrhea


Altered cognition


Defects in carbohydrate utilization



Causes


Intestinal disease


Sprue, Crohn’s Disease, short bowel syndrome


Eating grains high in phytic acid (inositol hexaphosphate)


May be an important consideration for strict vegetarians who
concentrate on grains.



NOTE: There is no agreed
-
upon clinical test for zinc




status.

Zinc’s Possible Role in
Treatment of Disease
-
1


“Common” Cold


The results of zinc lozenges are mixed.


There is risk of overdosing if these lozenges are used for
prolonged periods (6
-
8 weeks).


Zinc is an astringent and may irritate the mound and GI
tract.


Age
-
related macular degeneration.


Three is no evidence that zinc either causes or reduces the
risk of this disease.


There are ongoing trials of anti
-
oxidant vitamins and
selenium.


Diabetes mellitus


Zinc does affect glucose metabolism.


Patients with diabetes taking zinc supplements should
carefully monitor their blood
-
glucose levels.

Age
-
Related Macular Degeneration

Zinc’s Possible Role in
Treatment of Disease
-
2


Wound healing


This claim has been made for nearly 40 years.


There have been recommendations that zinc
supplements hastens healing of bed sores and
other forms of skin ulcerations.


Immune system


Zinc is required for a proper immune response.


There is some evidence that HIV/AIDS patients
may benefit from zinc supplements.


For these studies, it is important to check on the
nutritional status of HIV/AIDS patients.


Otherwise, the results are mixed that zinc
facilitates the immune response.

Zinc Toxicities


Zinc is a potent astringent.


Acute Symptoms


Many of the symptoms probably caused by zinc’s astringent
properties.


Epigastric pain


Nausea


Vomiting


Abdominal cramps


Diarrhea



Chronic Symptoms


Zinc competes with other metals at the transport sites.


Suppression of immune response


Decrease in HDL


Decrease in copper levels

Dosages Forms


Zinc acetate


Zinc gluconate


Zinc picolinate


No evidence that the zinc in this salt is
more bioavailable.


Zinc sulfate


Zinc oxide

Dietary Reference Intakes
-
1


AI


Infants (0
-
6 months)


2.0 mg/day



EAR


Infants (7
-
12 months)


2.5 mg/day


Children (1
-
3 years)


2.5 mg/day


Children (4
-
8 years)


4 mg/day


Children (9
-
13 years)


7 mg/day


Boys (14
-
18 years)


8.5 mg/day


Girls (14
-
18 years)


7.3 mg/day


Men (19
-
70+ years)


9.4 mg/day


Women (19
-
70+ years)


6.8 mg/day


Pregnancy (14
-
18 years)

10.0 mg/day


Pregnancy (19
-
50 years)

9.5 mg/day


Lactation (14
-
18 years)


10.9 mg/day


Lactation (19
-
50 years)


10.4 mg/day

Dietary Reference Intakes
-
2


RDA


Infants (7
-
12 months)


3 mg/day


Children (1
-
3 years)



3 mg/day


Children (4
-
8 years)



5 mg/day


Children (9
-
13 years)


8 mg/day


Boys (14
-
18 years)



11 mg/day


Girls (14
-
18 years)



9 mg/day


Men (19
-
70+ years)



11 mg/day


Women (19
-
10+ years)


8 mg/day


Pregnancy (14
-
18 years)


12 mg/day


Pregnancy (19
-
50 years)


11 mg/day


Lactation (14
-
18 years)


13 mg/day


Lactation (19
-
50 years)


12 mg/day

Dietary Reference Intakes
-
3


UL


Infants (0
-
6 months)



4 mg/day


Infants (7
-
12 months)


5 mg/day


Children (1
-
3 years)



7 mg/day


Children (4
-
8 years)



12 mg/day


Children (9
-
13 years)


23mg/day


Boys (14
-
18 years)



34 mg/day


Girls (14
-
18 years)



34 mg/day


Men (19
-
70+ years)



40 mg/day


Women (19
-
70+ years)


40 mg/day


Pregnancy (14
-
18 years)


34 mg/day


Pregnancy (19
-
50 years)


40 mg/day


Lactation (14
-
18 years)


34 mg/day


Lactation (19
-
50 years)


40 mg/day

Dietary Sources


Shellfish


Beef and other red meats


Nuts and legumes


The zinc in leavened whole grain
breads is more bioavailable.


Yeast consumes some of the phytic acid.