Overview Definition micronutrients required in the diet for necessary cellular functions Major examples iron (Fe) copper (Cu) zinc (Zn) chromium (Cr) fluoride (F) iodide (I) selenium (Se) Others V, Mo, Mn, Co, and Ni Function part of metalloenzyme enzyme has no activity without the metal metal is fixed metal:protein is constant example login to view 1 more bullet part of metal-containing enzyme enzyme may have activity without the metal metal is reversibly bound metal:protein ratio is variable example login to view 1 more bullet Oxidative stress organometallic side reactions that damage tissue many metals undergo the Fenton reaction in vivo login to view 3 more bullets heme iron can generate superoxide radicals (O2*) reactions happen frequently, but the body can defend itself with anti-oxidants oxidative stress occurs when pro-oxidants > anti-oxidants. examples of oxidative stress damage stroke Parkinson’s Alzheimer’s Iron Source diet recycled from destroyed erythrocytes Forms ferrous iron (Fe2+) dangerous causes oxidative stress found in hemoglobin ferric iron (Fe3+) less dangerous methemoglobinemia (metHb) occurs when Fe3+ is found in hemoglobin Absorption Fe-containing compounds are solubilized in low stomach pH Fe3+ is reduced to Fe2+ (requires vitamin C) in intestine so it can cross gut lumen ferroportin brings Fe3+ into bloodstream from enterocytes mediates amount of Fe released into the blood hepcidin inhibits ferroportin login to view 1 more bullet Storage must be immediately used or stored to prevent: bacterial utilization login to view 1 more bullet formation of iron oxides free radicals (Fe + O2) site hepatocytes (main) enterocytes macrophages stored as ferritin (Fe3+) hemosiderin binds excess Fe3+ to prevent from entering the blood Transport carried as Fe3+ by transferrin in the blood transferrin chelates the Fe3+ and transports it in the blood to tissues. login to view 4 more bullets ferroxidase (aka ceruloplasmin) oxidizes Fe2+ to Fe3+ for transport and storage ferritin can also oxidize Fe for storage Excretion no cellular mechanism for iron excretion lost from blood loss and removal of skin cells and other epithelial cells Toxicity beyond the sequestration capacity of ferritin causes oxidative stress Disorders in iron handling hereditary hemochromacytosis Copper Role human metabolism like other metals, free copper is potentially toxic by donating electrons creates hydroxyl radicals and other reactive oxygen species copper is a cofactor for many metalloproteins examples login to view 2 more bullets Transport albumin and ceruloplasmin carry copper in the blood similar role to transferrin in iron transport metallothionein is a carrier of copper, zinc, and many other metals role in preventing oxidative stress in the cell thiol groups from many cysteine residues mediate binding Excretion excess copper removed in the bile unlike iron with no mechanism of excretion Deficiency causes excess zinc login to view 2 more bullets symptoms a function of what enzymes require copper login to view 7 more bullets Disorders in copper handling Wilson's disease Menke’s disease X-linked gene mutation in ATP7A login to view 1 more bullet aka Ehlers-Danlos syndrome type IX inability of enterocytes to release absorbed copper copper at toxic levels in small intestine and kidneys copper in circulation and in brain at low levels symptoms login to view 5 more bullets Zinc Function hundreds of enzymes require zinc important examples login to view 3 more bullets Transport metallothionein carries zinc competes with copper Deficiency causes poor diet alcoholism login to view 1 more bullet symptoms impaired collagenase login to view 1 more bullet impaired zinc finger transcription factor motifs login to view 2 more bullets ↓ in senses login to view 2 more bullets diarrhea hair loss (alopecia) Chromium Deficiency causes total parenteral nutrition (TPN) symptoms a function of what proteins/enzymes require chromium login to view 2 more bullets Flouride Source mainly fluoridated water Deficiency plays a role in bone and teeth formation/strength ↑ bone fractures dental caries Iodine Source mainly iodized salt Deficiency plays a role in synthesis of thyroid hormone goiter ↓ thyroid hormone output Selenium Deficiency causes total parenteral nutrition (TPN) symptoms plays a role in glutathione peroxidase that protects against oxidative stress login to view 3 more bullets