nutrition topic patommatat md zinc chromium copper
TRANSCRIPT
Nutrition topic
Patommatat MD
Zinc
Chromium
Copper
What is Zinc ?
• Chemical element• Atomic number 30• Zn2+ = common oxidation
state
Zinc
Biochemical and physiological function
300 Human enzymes
Example :
RNA polymerase I,II,III
ALP
Carbonic anhydrase
ApometalloenzymeZn
Zinc Metalloenzyme
1. Catalytic function
Biochemical and physiological function
Cause Protein folding Example :
Zinc finger motif Loss Zinc
alter protein folding
Loss of protein function
2. Structural function
Biochemical and physiological function
Gene responsiveness Receptor-mediated signal
transduction Antigen-dependent T-cell fn
3. Regulatory function
Transcription factor “Zif268”
DNA
Zn
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
Zinc turnover
• 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 ?• 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
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)
• Chemical element• Atomic number 29• Cu2+ common
oxidative state
What is Copper ?
Copper
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
• Metallothionine: Metal storage in liver• Albumin : Prevent intravascular toxicity• Transcuprein : Role may be a transportor• Factor V, VIII : Role not known
Physiologic function• Connective tissue formation• Iron metabolism & erythropoiesis• Myelin formation (Required ATP)• Neurotransmitter: NE,DA,E• Melanin formation:
Albinism if defect
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
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
Copper deficiency• Anemia : Hypochromic normocytic• Osteoporosis in growing bone• Neutropenia• Other not well established:
– Arthritis– Depigmentation– Myocardial disease– Neurologic effect demyelination
Food source
• Rich source• Intermediate source• Low amount
• 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
What is Chromium ?
• Chemical element• Atomic number 24• 2 common form
– Trivalent form (CrIII)– Hexavalent form (CrVI)
Chromium
Nicotinate
Picolinate
Cr(III)
Bind with ligands
Cr(VI)
Acetate
Gastric acid
Strong oxidizing
agent
(Chromate & Dichromate)
Irritating & potential hazard
Food
Chromium picolinate
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 insulinsensitivity in vivo. J Trace Elem Exp Med1999;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
Normal person DiabetesHypoglycemiaLow G/I ratio High G/I ratioBalance G/I ratio
Balance G/I ratio
[chromium deficient state]
[After chromium supplementation]
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
Insulin Receptor
Tyrosine kinase protein receptor
Low molecular weight Chromium
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
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• 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 !!
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.
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