nutrition topic patommatat md zinc chromium copper
TRANSCRIPT
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Nutrition topic
Patommatat MD
Zinc
Chromium
Copper
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What is Zinc ?
• Chemical element• Atomic number 30• Zn2+ = common oxidation
state
Zinc
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Biochemical and physiological function
300 Human enzymes
Example :
RNA polymerase I,II,III
ALP
Carbonic anhydrase
ApometalloenzymeZn
Zinc Metalloenzyme
1. Catalytic function
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Biochemical and physiological function
Cause Protein folding Example :
Zinc finger motif Loss Zinc
alter protein folding
Loss of protein function
2. Structural function
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Biochemical and physiological function
Gene responsiveness Receptor-mediated signal
transduction Antigen-dependent T-cell fn
3. Regulatory function
Transcription factor “Zif268”
DNA
Zn
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Zinc excretion
• Sloughing of mucosal cells• Pancreatic secretion• Trans-epithelial flux
1. GI 2. urine
• 1 mg/d in normal• Increased with muscle protein
catabolism Zn bound with amino acid pass kidney filter3. Others
• 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
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Zinc turnover
• Recycling by Erythron• 20-40 μgZn/gHb• 750 g in adult Hb• Turnover of Zn pool
0.12 - 0.25 mg/d
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How can we loss Zinc ?• Absorption
– Diarrhea– Pancreatic
insufficiency– Inflammatory bowel
diseases
• Protein catabolism– Stress / sepsis– Nephrotic syndrome
• Skin loss – burn, pemphigus, EM
• Increased requirement– Pregnancy– Lactation– Infant, children,
Adolescence
• Prolonged intake of High phytate diet
• Not taking Zinc containing diet : TPN
• Peritoneal dialysis
Other condition • Alcoholism hyperzincuria• DM• Infection• Zn chelator : penicillamine
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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
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Food source
• Organ & flesh
High Zn No phytate• Egg & Dairy food
Low Zn No phytate• Cereal & legumes
Low Zn High phytate
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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 !!
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Acrodermatitis enteropathica
Erythematous patch with crusted vesicles
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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)
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• Chemical element• Atomic number 29• Cu2+ common
oxidative state
What is Copper ?
Copper
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Copper Biochemistry
• Cu-containing enzyme• Cu-binding protein• Low molecular wt. ligands
– Histidine, Cystine, Glutamine, Threonine– Peptides
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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
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Copper binding protein
• Metallothionine: Metal storage in liver• Albumin : Prevent intravascular toxicity• Transcuprein : Role may be a transportor• Factor V, VIII : Role not known
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Physiologic function• Connective tissue formation• Iron metabolism & erythropoiesis• Myelin formation (Required ATP)• Neurotransmitter: NE,DA,E• Melanin formation:
Albinism if defect
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Copper in diet
Absorbed through intestinal mucosa 2%
Remaining
unabsorbed Cu 98%Liver
Tissues
skin hair
Intes tract
ceruloplasmin
Delivery Cu to
Peripheral tissues Secrete Endogenous Cu
FecesAlbumin
LMW ligands
Portal v. by Albumin, Transcuprein, LMW ligands
Copper Elimination
Extra-gastrointestinal route
Cu2+
Cu2+
Copper route
In human body
Bile
kidney
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Risk of Copper deficiency• 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
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Copper deficiency• Anemia : Hypochromic normocytic• Osteoporosis in growing bone• Neutropenia• Other not well established:
– Arthritis– Depigmentation– Myocardial disease– Neurologic effect demyelination
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Food source
• Rich source• Intermediate source• Low amount
• Shellfish• Nuts• Seeds• Legumes• Liver • Organ meat• Bran & germ portion of grains
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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
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Copper toxicity• Copper excess from metallothionine in liver
begin to damage liver and other tissue– Liver– CNS
• High serum free copper• Low serum ceruloplasmin
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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
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What is Chromium ?
• Chemical element• Atomic number 24• 2 common form
– Trivalent form (CrIII)– Hexavalent form (CrVI)
Chromium
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Nicotinate
Picolinate
Cr(III)
Bind with ligands
Cr(VI)
Acetate
Gastric acid
Strong oxidizing
agent
(Chromate & Dichromate)
Irritating & potential hazard
Food
Chromium picolinate
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Biologic Activity• Glucose homeostasis• Lipid profile• May be good for osteoporosis
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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.
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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
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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 insulinsensitivity in vivo. J Trace Elem Exp Med1999;12:71-83.
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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.
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Glucose homeostasis : In view of Glucose/Insulin Axis
Normal person DiabetesHypoglycemiaLow G/I ratio High G/I ratioBalance G/I ratio
Balance G/I ratio
[chromium deficient state]
[After chromium supplementation]
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Glucose tolerance factorUse 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
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Insulin Receptor
Tyrosine kinase protein receptor
Low molecular weight Chromium
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Factor influencing Cr absorption
• 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
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Chromium Deficiency• 2 Case reports ; both on non-Cr addd TPN• Symptoms
– Severe hyperglycemia– Rapid wt. loss– Decreased RQ (increased fat utilization)
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Adequate intake
Age (yr) Female (μg/d) Male (μg/d)
19-50 35 25
≥ 51 30 20
Food source• 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 !!
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Free radical generationBy Chromium(III) picolinate
Mutagenic effect !!
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.
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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