Transcript Chromium

Discovery
• Discovered in 1797 by N.-L. Vauquel
• Common name: Chrome
• Origin of name: From the Greek word
Chroma (means color).
Short Historical
perspective
• Early 1900s – Cr became an important
ingredient in corrosion-resistant metals
• 1959 - Schwartz & Mertz identify Cr as
active “Glucose Tolerance Factor” (GTF)
– Later: chromium was thought of as a cofactor with
insulin, necessary for normal glucose utilization
– Inorganic salt of chromium were utilized poorly
compared to an organically bound form of chromium
present in brewer's yeast
Short Historical
perspective
• 1974 - Polansky shows that the active
principle of GTF is a Cr-niacin complex
• 1975 - Jeejeebhoy makes first report of
human Cr deficiency
– Total parenteral nutrition (TPN) deficient in Cr
Facts
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Symbol Cr and atomic number 24
Atomic weight: 51.9961 g/mol
Transition metal
25th most abundant
Steel-gray
Mostly known as the “chrome” plating on
cars, or the shiny metal in the bathroom
More facts
• Exists in multiple valence states
– Absorption, tissue distribution and toxic potential
varies with valence state
• Food supply Cr is in +3 valence
• Most toxic Cr is in +6 valence, strong oxidizer
• +3Cr complexes
– Cr slowly exchanges in and out of complexes, so Cr is
not thought to be part of any metalloenzymes
– GTF (glucose tolerance factor) was thought to be a
complex containing Cr, niacin and amino acids
Chromodulin
• Oligopeptide
– Bovine liver: glycine:cysteine:glutamate:aspartate
(2:2:4:2)
• Also contains carboxylate substituents on more than half
of amino acids.
• Ratio of amino acids varies between milk and liver forms
– Coordinate cluster of 4, Cr+3
• Binding is tight and highly co-operative
Chromodulin
• Mechanism
– Apochromodulin
• Found in insulin sensitive cells
– Holochromodulin
• In the presence of insulin activates insulin-dependent
protein tyrosine kinase activity
• Concentration dependent – Chromium must be in
apochromodulin
– Autoamplification system for insulin signalling
Chromodulin
Insulin
Holochromodulin then enhances
insulin receptor function
Insulin
Insulin
Insulin
Insulin
Tyr-P
Cr
Cr
Transferrin
Chromium Influx
Cr
Cr
Cr
Cr
holochromodulin
apochromodulin
Chromium binds to apochromodulin
converting it to holochromodulin
Requirements
• Infants
Adequate intake
– 0-6 mo: 0.2 ug/d
– 7-12 mo: 5.5 ug/d
• Children and adolescents
– 1-8 yrs: 11 - 15 ug/d
– 9-15 yrs: 21 - 25 ug/d
• Adults
– 14- 50 yrs: Male = 35 ug/d
Female = 25 ug/d
– >50 yrs: Male = 30 ug/d
Female = 20 ug/d
Females
– Pregnant women: 29-30 ug/d
– Lactating women: 44-45 ug/da
• Animals
– less than 50ug/kg diet are
deficiency provoking
– 1mg CrKSO4/kg diet
adequate in most cases
– Most get adequate
amounts from
unsupplemented feed.
No upper intake levels
set due to lack
of data
Toxic level >500
mg/d
(human)
Sources and distribution
• High (30-200 mg/100 g)
– Oysters, calves liver, egg yolk, peanuts, grape juice
(acid/stainless), American cheese, wheat, wheat germ,
molassas, black pepper
• Medium (13-30 mg/100 g)
– Shrimp, beef & lamb liver, heart or kidney, eggs, brown rice,
orange juice, potato, butter, margarine, syrups & brown
sugars
• Low (0-12 mg/100 g)
– Haddock, lobster, muscle meats, polished rice or barley,
most other fruits & veges, oil, milk, light sugars, mushrooms
Distribution
• Widely distributed, but at very low
concentrations
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Grains & cereals > fruits & vegetables
Processing may add or remove Cr
Acidic foods leach Cr from stainless steel
Processed meats usually high in Cr
• Limited information on Cr
– Very low levels make quantitation difficult
• at or below limit of detection for many methods
Analytical methodology
• Chromium concentrations in body tissues
or fluids and in foods can be determined
by three methods:
- dual-label isotope spectrometry
- radiochemical neutron activation analysis
- Graphite furnace atomic absorption spectrometry
• Collection and processing requires uch
care to avoid contamination
Absorption
• Poorly absorbed
- Approximately 0.5 % to 2.4 % is absorbed of daily intake
• People with diabetes absorb 2 -4 times more Cr
• Cr is absorbed primarily in the small intestine
• Incorporated into kidney, spleen, liver, lungs,
heart and skeletal muscle
• Transported to tissue by transferrin
• Absorbed Cr is excreted primarily in the urine
Function
• Cr act cooperatively with other
substances, such as:
- Hormone (insulin)
- Various enzymes
- The genetic material of the cell
(DNA and RNA)
Deficiency
• Situations
– Infants and children malnutrition:
diabeticlike disorder of metabolism
– Impaired glucose tolerance
– Disturbances in lipid and protein
metabolism
– TPN patients (weight loss)
Toxicity
• Trivalent Cr
– Have not been shown to be toxic to humans or animals
• Hexavalent Cr
(we all saw Erin Brockavich)
– Is taken up easily
– Toxicity more likely if inhaled, can cause carcinoma of the
bronchial system
– Is postulated that it binds to DNA
– Acute: GI ulceration, CNS symptoms
– Chronic: Depressed growth, liver and kidney damage
• Think cancer effects might occur as a
result of Cr+6 -> Cr+3
Conclusion
• Chromium in the trivalent form is an essential
nutrient
• Chromium functions in glucose metabolism, by
regulating insulin
• Insufficient dietary intake of Cr is associated
with increased risk factors associated with
type II diabetes mellitus and cardiovascular
diseases
• The mechanisms of absorption and transport
of chromic ions are still uncertain