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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 • • • • • • 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 – – – – 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