Quiz 4: Zinc Flashcards
body contains __g of zinc
body contains 1.5-3g of zinc
where is zinc found in the body
ALL organs, tissues, and body fluids
2 organs with most zinc
muscle
bone
zinc is a metal that can exist in several __, but is most found as the __ ion (__)
zinc is a metal that can exist in several valence states, but is most found as the divalent ion (Zn2+)
zinc is found in foods complexd with __ and __ that are part of __ and __
zinc is found in foods complexd with nucleic acids and amino acids that are part of peptides and proteins
food sources of zinc
red meats (organs)
seafood (oysters)
poultry, pork
dairy
__ products provide 40-70% of zinc consumed by most people in the US
animal products provide 40-70% of zinc consumed by most people in the US
in US, other 30% of zinc is provided by
cereals
zinc from __ has lower absorption
zinc from plants has lower absorption
factors that inhibit zinc’s availability
- heating
- maillard reaction products (amino acid-carb complexes) from browning
supplement forms of zinc
- zinc oxide
- zinc sulfate
- zinc acetate
- zinc chloride
- zinc gluconate
how should zinc supplements be consumed?
on an empty stomach without simultaneously ingesting other mineral supplements (Fe, Ca)
side effects of zinc supplements
abdominal pain
dyspepsia
nausea, vomiting, diarrhea
topical zinc products form
zinc oxide
zinc chloride
what is topical zinc used for
wound managements
percutaneous absorption of zinc depends on skin’s __ and requires __ on skin’s surface
percutaneous absorption of zinc depends on skin’s integrity and requires acidic moisture on skin’s surface
less intact skin = __ zinc absorbed
less intact skin = more zinc absorbed
in presence of intact skin barrier, zinc binds to __ groups in epidermal __ upon release from zinc oxide or chloride salt in __ environment
in presence of intact skin barrier, zinc binds to sulfhydryl groups in epidermal keratin upon release from zinc oxide or chloride salt in acidic environment
how long does it take to absorb zinc after topical application
60 minutes
zinc that doesn’t get into circulation, binds to __ in epidermal ketatinocytes and is eventually __ with skin cell turnover __
zinc that doesn’t get into circulation, binds to metallothionein in epidermal ketatinocytes and is eventually sloughed off with skin cell turnover
endogenous zinc from __, __, and __ secretions is released into GI tract with food ingestion and augments zinc present from __ and __
endogenous zinc from pancreatic, intestinal, and biliary secretions is released into GI tract with food ingestion and augments zinc present from dietary food sources and supplements
zinc secreted into GI tract can be __, important for zinc homeostasis
zinc secreted into GI tract can be reabsorbed, important for zinc homeostasis
zinc absorption location
proximal small intestine:
duodenum + upper jejunum
2 mechanisms of of zinc absorption
- carrier-mediated transport
- diffusion
primary method of zinc absorption (with usual intake)
saturable
carrier mediated
ZIP4
major transporter of zinc across enterocyte’s brush border membrane
ZIP4
ZIP4 aka
Zrt and Irt like protein 4
ZIP4 is expressed throughout
GI tract
with high Zinc intakes, ZIP4 is degraded __ rapidly to __ absorption
with high Zinc intakes, ZIP4 is degraded more rapidly to downregulate absorption
zinc restriction enhances ZIP4 __ which rapidly __ ZIP4 synthesis and shifts ZIP4 proteins to __
zinc restriction enhances ZIP4 mRNA stability which rapidly induces ZIP4 synthesis and shifts ZIP4 proteins to brush border membrane
enhanced ZIP4 synthesis is mediated by upregulation of __ which binds __ region on ZIP4 gene
enhanced ZIP4 synthesis is mediated by upregulation of transcription factor KLF4 which binds promoter region on ZIP4 gene
digestion, absorption, transport of zinc steps
- bound zinc released from food
- zinc absorbed by ZIP4 in brush border
- DMT1 and amino acids play minor role across brush border
- zinc bound by inhibitors goes into feces, absorption can be enhanced by organic acids, decreased pH, or chelators
- high zinc intake = paracellular absorption
- within cells, zinc used or stored in vesicles (in trans-Golgi network) or as part of metallothionein
- zinc transported across basolateral by ZnT1
- zinc binds proteins for transport in the blood
mutation in ZIP4 causes
acrodermatitis enteropathica
acrodermatitis enteropathica
poor zinc absorption
skin lesions
impaired growth
low plasma zinc
can be fatal
how to treat acrodermatitis enteropathica
high doses of zinc (forces paracellular diffusion)
what amino acid can bind zinc to allow it to enter enterocyte
histidine
what other ZIP is found on brush border and when is it upregulated
upregulated with zinc restriction
ZIP11
__% of zinc is absorbed from the typical US diet
20-50% of zinc is absorbed from the typical US diet
fractional zinc absorption varies from __
higher intakes = absorption __
fractional zinc absorption varies from 10-80%
higher intakes = absorption diminishes
enhancers of zinc absorption
- glutathione
- organic acids (citric acid, picolinic acid)
- amino acids
- low pH
GOAL
inhibitors of zinc absorption
- high pH
- phytic acid
- oxalic acid
- polyphenols
- selected nutrients
HiPOPS
__ and products of protein digestion (__ and __) enhance zinc absorption
glutathione and products of protein digestion (tripeptides and amino acids) enhance zinc absorption
zinc binds to sulfur (__ alone, or part of __) and nitrogen (__)
zinc binds to sulfur (cysteine alone, or part of glutathione) and nitrogen (histidine)
antacids __ gastric and proximal instestinal pH and __ zinc absorption
antacids increase gastric and proximal instestinal pH and decrease zinc absorption
inhibitors of zinc sources:
phytic acid:
oxalic acid
polyphenols:
other minerals:
inhibitors of zinc sources:
phytic acid: plant foods (legumes, nuts)
oxalic acid: spinach, berries, chocolate, tea
polyphenols: tea, coffee, fibers
other minerals: iron and calcium
zinc supplement should not be consumed at same time as a __ supplement on a __ stomach
zinc supplement should not be consumed at same time as a nonheme supplement on a empty stomach
zinc supplements should also not be taken with
other minerals
3 options for zinc use within enterocyte
- functinal use in enterocyte
- stored in enterocyte
- transported through cytosol to enter blood and be used by other tissues
most zinc that isn’t used is __ or bound to __
most zinc that isn’t used is sequestered or bound to proteins
do we have free zinc
very little
ZnT7 functions
inside cell
moves zinc into trans-Golgi network
ZIP7 function
transport out of trans-Golgi network
metallothionein function
zinc’s main short-term storage protein
IC binding ligand
metallothionein has a strangely high amount of __ which helps with __ binding
metallothionein has a strangely high amount of cysteine which helps with metal binding
2 main functions of metallothionein
- transport zinc to zinc-requiring enzymes
- store zinc transiently
how does zinc exit enterocyte and enter blood
ZnT1 transports zinc out of duodenal and jejunal cells (in exchange for H+ or K+)
what does ZnT1 require
nothing
ZnT1 expression
increased with high zinc intake
not affected by low
in addition to ZnT1, __ on basolateral membrane sends zinc into blood
in addition to ZnT1, DMT1 on basolateral membrane sends zinc into blood
zinc form in portal blood
loosely bound to albumin
after blood zinc is taken up by
liver
which ZIP transports zinc into hepatocytes and is increased during infections and trauma
ZIP14
which ZIP is expressed in intestine, pancreas, liver, kidney
mucosal zinc transport (blood to intestine)
ZIP5
where is zinc found in body
ALL tissues/organs
mostly liver, kidneys, muscle, skin, and bones
within cells
__% of zinc bound to proteins in nucleus
__% in cytosol
rest in __
within cells
30-40% of zinc bound to proteins in nucleus
50% in cytosol
rest in cell membranes
zinc is stored attached to
metallothionein
metallothionein other functions
- antioxidant
a metal trxn factor reliant on zinc binds __ to induce thionein synthesis
a metal trxn factor reliant on zinc binds MRE to induce thionein synthesis
zinc roles
- facilitates biochemical rxns
- metabolic pathways
- gene expression (trxn factors)
zinc dependent enzymes
metalloenzymes
rxns zinc has a role in
- acid-base balance
- phosphate release
- aldehyde synthesis
- protein digestion
- heme synthesis
- antioxidant
- phospholipid metabolism
- folate digestion
- wound repair
- nucleic acid synthesis and cell replication and growth
zinc role in gene expression
zinc fingers
other roles of zinc
- cell membranes
- insulin (carb metabolism)
- basal metabolic rate
- immune function
pharmacological uses of zinc
colds
eye health
zinc and vitA
zinc deficieny prevents vitA mobilization
excess zinc impacts __ absorption
excess zinc impacts copper, calcium absorption
__ in high conc competes for zinc binding sites
cadmium in high conc competes for zinc binding sites
zinc excretion methods
GI tract: feces
kidneys
skin: semen and menses
which ZIP and ZnT facilitate excretion in feces
ZIP5 and ZnT6
zinc deficiency in children symptoms
growth retardation
skeletal abnormalities
poor wound healing
diarrhea
rash
zinc deficiency in adults symptoms
anorexia
diarrhea
lethargy
depression
vision problems
wound healing
populations at risk for deficiency
older adults
vegetarians
alcoholics
low SES
thiazide diuretics (increase zinc excretion)
zinc toxicity
metallic taste
headache, nausea, vomiting, cramps, bloody diarrhea
chornic low zinc can cause __ deficiency
chornic low zinc can cause copper deficiency
assessing zinc status
fasting serum or plasma
