Download Zinc

Nutrition topic
Zinc
Copper
Chromium
Patommatat MD
Zinc
What is Zinc ?
• Chemical element
• Atomic number 30
• Zn2+ = common
oxidation state
Biochemical and physiological function
1. Catalytic function
Zn
Apometalloenzyme
Zinc Metalloenzyme
300 Human enzymes
Example :
RNA polymerase I,II,III
ALP
Carbonic anhydrase
Biochemical and physiological function
2. Structural function
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Cause Protein folding
Example :
Zinc finger motif
Loss Zinc
 alter protein folding
 Loss of protein function
Biochemical and physiological function
3. Regulatory function
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DNA

Zn
Transcription factor “Zif268”
Gene responsiveness
Receptor-mediated signal
transduction
Antigen-dependent T-cell fn
Zinc excretion
2. urine
1. GI
• Sloughing of mucosal cells • 1 mg/d in normal
• Increased with muscle protein
• Pancreatic secretion
catabolism  Zn bound with
• Trans-epithelial flux
amino acid  pass kidney
filter
3. Others
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Integument 1mg/d
Menstruation 0.1-0.5mg total
Semen 1mg/ejaculation
Parturition 100mg/fetus & placenta
Lactation 2.2mg/d at wk 4
0.9mg/d at wk 35
Zinc turnover
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Recycling by Erythron
20-40 μgZn/gHb
750 g in adult Hb
Turnover of Zn pool
0.12 - 0.25 mg/d
How can we loss Zinc ?
• Increased requirement
• Absorption
– Pregnancy
– Lactation
– Infant, children,
Adolescence
– Diarrhea
– Pancreatic
insufficiency
– Inflammatory bowel
diseases
• Protein catabolism
– Stress / sepsis
– Nephrotic syndrome
• Skin loss
• Prolonged intake of
High phytate diet
• Not taking Zinc
containing diet : TPN
• Peritoneal dialysis
– burn, pemphigus, EM
Other condition
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Alcoholism  hyperzincuria
DM
Infection
Zn chelator : penicillamine
Phytate
• principal storage form of
phosphorus in many plant
tissues, especially bran and
seeds
• strong chelator of important
minerals such as calcium,
magnesium, iron and zinc
• contribute to mineral
deficiencies in developing
countries
Food source
• Organ & flesh
High Zn No phytate
• Egg & Dairy food
Low Zn No phytate
• Cereal & legumes
Low Zn High phytate
Zinc deficiency : How to identify?
• Clinical setting
– Low dietary intake
– Risk people : Alcohol, High prot. catabolism
• Clinical sign
– Dermatitis
– Defect in immune function
– Growth retardation & Delayed sexual
maturation
• Functional response to supplemental Zn
No lab can
completely
identify !!
Acrodermatitis enteropathica
Erythematous patch with
crusted vesicles
Role of Zinc in Nutritional support
• Burn patient
• Supplement in zinc def patient
How we replace zinc ?
1. Oral replacement : Zinc acetate solution
• Dose : 5-10 ml oral bid
2. TPN : Addamel N
• Zinc 6.5 mg/10ml (100μmol)
Copper
What is Copper ?
• Chemical element
• Atomic number 29
• Cu2+ common
oxidative state
Copper Biochemistry
• Cu-containing enzyme
• Cu-binding protein
• Low molecular wt. ligands
– Histidine, Cystine, Glutamine, Threonine
– Peptides
Important Copper containing enzyme
• Lysyl oxidase  Cross-link Elastin and
collagen fiber
• Feroxidase I = Ceruloplasmin  Transfer Iron
from storage site to Hb synthetic site
• Cytochrome C oxidase  generate ATP
• Superoxide dismutase(SOD) Free radical
scavenger  prevention of cell damage
• Tyrosinase  melanin synthesis
Copper binding protein
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Metallothionine:
Metal storage in liver
Albumin : Prevent intravascular toxicity
Transcuprein : Role may be a transportor
Factor V, VIII : Role not known
Physiologic function
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Connective tissue formation
Iron metabolism & erythropoiesis
Myelin formation (Required ATP)
Neurotransmitter: NE,DA,E
Melanin formation:
Albinism if defect
Copper route
Copper in diet
In human
body
Absorbed through
intestinal mucosa 2%
Portal v. by Albumin,
Transcuprein,
LMW ligands
Liver
Cu2+
ceruloplasmin
Cu2+
Remaining
unabsorbed Cu 98%
Delivery Cu to
Peripheral tissues
Secrete Endogenous Cu
Tissues
Bile
Intes tract
kidney
skin
hair
Albumin
LMW ligands
Feces
Extra-gastrointestinal route
Copper Elimination
Risk of Copper deficiency
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Increased GI loss : Diarrhea, fistula
TPN
Prolonged antacid use
High dose Zinc supplementation: sickle cell
Severe handicapped Patient
Cystic fibrosis
Infant : Premature Breast fed, Chr. PD
Copper deficiency
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Anemia : Hypochromic normocytic
Osteoporosis in growing bone
Neutropenia
Other not well established:
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Arthritis
Depigmentation
Myocardial disease
Neurologic effect  demyelination
Food source
• Rich source
• Intermediate source
• Low amount
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Shellfish
Nuts
Seeds
Legumes
Liver
Organ meat
Bran & germ portion of grains
Recommendation
• Recommended dietary allowance (RDA)
0.9 mg/d
• Tolerable upper intake level (UL)
10 mg/d
• Pregnancy
RDA= 1 mg/d
• Lactation
RDA= 1.3 mg/d
Copper toxicity
• Copper excess from metallothionine in liver
begin to damage liver and other tissue
– Liver
– CNS
• High serum free copper
• Low serum ceruloplasmin
Conclusion : point in clinical practice
• Copper deficiency found in Prolonged NPO
Pt with NON – Copper added TPN
• Beware copper supplement in cholestasis
liver disease  copper toxicity
Chromium
What is Chromium ?
• Chemical element
• Atomic number 24
• 2 common form
– Trivalent form (CrIII)
– Hexavalent form (CrVI)
Food
Cr(VI)
Gastric acid
Strong
&
oxidizing (Chromate
Dichromate)
agent
Cr(III)
Bind with
ligands
Chromium
picolinate
Picolinate
Acetate
Irritating &
potential
hazard
Nicotinate
Biologic Activity
• Glucose homeostasis
• Lipid profile
• May be good for osteoporosis
History
• Discovery of Glucose tolerance
factor (GTF) in yeast ; 1929
• Rats fed with Torula yeast-based
diet began to show signs of glucose intolerance
• Reversed by a diet of brewers yeast
Mertz W, Schwarz K. Relation of glucose tolerance factor to impaired intravenous glucose tolerance of
rats on stock diets. Am J Physiol 1959;196:614-618.
Schwartz K, Mertz W. A glucose tolerance factor and its differentiation from factor 3. Arch Biochem
Biophys 1957;72:515-518.
Benefit Even in Healthy
• 200 mcg/d Cr picolinate in healthy subjects
for 7 wks
– Decreased FBG 8%
– Increased Fasting insulin significantly 28%
Diabetics
• 200 mcg/d Cr picolinate in hyperglycemic
subjects for 3 mos
– Lower glucose level
– Lower insulin use
– Improve glucose tolerance
People with high risk
• 1000 mcg/d Cr picolinate in people with
obesity and FH of DM type 2 for 8 mos
– Increased Insulin enhanced Glucose
clearance  increased Ins sensitivity
– Inhibition of Hepatic glucose production
Cefalu WT, Bell-Farrow AD, Stegner J, et al.
Effect of chromium picolinate on insulin
sensitivity in vivo. J Trace Elem Exp Med
1999;12:71-83.
Benefit on Hypoglycemia ALSO !!
• Placebo-controlled crossover trial
• 200 mcg/d CrCl3 for 3 mos
• Alleviating symptoms of Hypoglycemia
• Raising minimum Glucose level 2-4 hr after
glucose challenge
Anderson RA, Polansky MM, Bryden NA, et
al. Effects of supplemental chromium on
patients with symptoms of reactive
hypoglycemia. Metabolism 1987;36:351-355.
Glucose homeostasis :
In view of Glucose/Insulin Axis
[chromium deficient state]
Hypoglycemia
Low G/I ratio
Normal person
Diabetes
Balance G/I ratio
High G/I ratio
[After chromium supplementation]
Balance G/I ratio
Glucose tolerance factor
Use to define Organic chromium degradation
product from yeast
Low molecular- weight chromium
binding substance (LMWCr)
 Found in Mammalian tissue
 Many ways similar to GTF
 Composed of : cysteine, glutamate, aspartate, Glycine
 store in cytosol of insulin-sensitive cell
 Stimulation of tyrosine kinase activity  insulin
signalling
Insulin Receptor
Tyrosine kinase
protein receptor
Low molecular
weight Chromium
Factor influencing Cr absorption
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Chromium extent in diet
Ascorbic acid  enhanced Cr absorption
Other metal def state  Zn or Fe def
Antacids  Decreased Cr absorption
ASA & Indometacin  enhanced Cr absorption
Chromium Deficiency
• 2 Case reports ; both on non-Cr addd TPN
• Symptoms
– Severe hyperglycemia
– Rapid wt. loss
– Decreased RQ (increased fat utilization)
Adequate intake
Age (yr)
Female (μg/d)
Male (μg/d)
19-50
35
25
≥ 51
30
20
Food source
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All food supply in small amount
More in whole grain & cereals
Refined sugar < less refined product
High Cr in processed meat
Acidic food received Cr from stainless steel packing !!
Adverse effect of Chromium
Steams D M, Wise J P Sr, Patiemo Sr, Wetterhahn K E.
Chromium (III) picolinate produces chromosome damage in
Chinese hamster ovary cells. FASEB J 1995; 9: 1643-1648.
Free radical
generation
By Chromium(III)
picolinate
Mutagenic effect !!
Wrong use of chromium !!
• Losing weight agents
• Muscle building agent
• No study shown benefit !!
Conclusion : point in clinical practice
• Chromium may be used as alternative Rx in
DM  need further study
• Chromium deficiency is seen in Prolonged
use of Non-Chromium added TPN