Chromium

1. Chromium By: Helle Nielsen

2. Discovery • Discovered in 1797 by N.-L. Vauquel • Common name: Chrome • Origin of name: From the Greek word Chroma (means color).

3. 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

4. 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

5. Facts • 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

6. 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

7. 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

8. 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

9. Chromodulin Insulin Holochromodulin then enhances insulin receptor function Insulin Insulin Tyr-P holochromodulin Insulin Insulin Cr Cr Transferrin Cr apochromodulin Chromium Influx Cr Cr Cr Chromium binds to apochromodulin converting it to holochromodulin

10. Infants 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. Requirements Adequate intake No upper intake levels set due to lack of data • Toxic level >500 mg/d • (human)

11. 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

12. Distribution • Widely distributed, but at very low concentrations • 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

13. 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

14. 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

15. Function • Cr act cooperatively with other substances, such as: - Hormone (insulin) - Various enzymes - The genetic material of the cell (DNA and RNA)

16. Deficiency • Situations • Infants and children malnutrition: diabeticlike disorder of metabolism • Impaired glucose tolerance • Disturbances in lipid and protein metabolism • TPN patients (weight loss)

17. 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

18. 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