Flashcards in Metabolism - Exam #4, Part Three Deck (77):
What is Selenium?
-NONMETAL and has several oxidation states;
-Chemistry of selenium is similar to SULFUR and selenium can substitute for sulfur
What are the sources of Selenium?
-Selenium varies greatly in its soil concentrations throughout the world so plant products are especially VARIABLE ;
-ORGAN meats and muscle meats are usually GOOD sources;
What are the forms of Selenium found in foods?
-Selenium in foods is in ORGANIC form =
1. selenomethionine (plant products )
2. selenocysteine (animal products) (Figure 12.14)
-INORGANIC forms are found in PLANT products
How is Selenium absorbed?
-Inorganic and organic selenium forms are absorbed in small intestine, but more in DUODENUM;
-Selenoamino acids absorbed by amino acid transporters
How is Selenium transported in the blood?
-In BLOOD selenium is bound to alpha- and beta-globulins and VLDL and LDL → these are associated;;
-Also selenoprotein P
How is Selenium stored?
TISSUES with the highest selenium =
1. Thyroid gland
How is Selenium metabolized?
0Metabolism involves formation of FREE selenium (Se), which is typically converted to selenide (H2Se);
-Selenide can be..
1/ Methylated (add –CH3) and excreted in urine or;
2. Converted to selenophosphate for incorporation into selenoproteins;
-Inorganic selenium also converted to selenide → Inorganic from plant products
What are the functions of Selenium?
-Glutathione peroxidase = most clearly established function → Selenium-dependent!;
-The 5’-deioidinase (iodide) is selenium-dependent enzyme involved in THYROID HORMONE metabolism
How is Glutathione Peroxidase selenium-dependent?
-Selenium is a COFACTOR for glutathione peroxidase;
-Glutathione peroxidase catalyzes removal of hydrogen peroxide and hydroperoxides → MORE ACTIVE than catalase enzyme;
-Catalase enzyme – catalyzes decomp. of H2O2 to water and oxygen
What other nutrients does Selenium interact with?
-IRON and COPPER deficiencies reduce glutathione peroxidase with mechanism unknown;
-Selenium DEFICIENCY would affect thyroid hormone synthesis (iodine);
-Oxidized GLUTATHIONE must be reduced by glutathione reductase, which is a flavoenzyme
How is Selenium excreted?
-EQUALLY in urine and feces → Excretion allows for homeostasis of selenium;
-Several urinary metabolites;
-Also can excrete from skin and lungs;
-With HIGHER intakes excrete DIMETHYLSELENIDE excreted by lungs and it smells like garlic
What are the recommendations for Selenium?
-RDA: Adult men and women = 55 µg/day;
-Based on balance studies and repletion studies in people in China in regions deficient in selenium and plateaus of select selenoproteins were chosen as the marker
What results from a toxicity of Selenium?
-Selenium toxicity is know as SELENOSIS → miners and supplement users have symptoms;
**UL = 400 µg/day
How is Selenium status assessed?
-Blood selenium is thought to reflect dietary intake;
-7 µg/dl is the cutoff for deficiency
What is Chromium?
-Chromium is a METAL;
-The TRIVALENT form (Cr3+) is thought to be important in human nutrition;
-Content in human body is estimated at ~4 to 6 mg
What are the sources of Chromium?
-Meats, fish and poultry, especially organ meats and whole grains are good sources;;
-Cheese, dark chocolate, several vegetables and fruits, spices and tea, beer and wine;
-Brewer’s yeast may have the organically complexed form known as glucose tolerance factor (GTF);
-Food processing has an effect:
o molasses and brown sugar have more than white sugar;
o stainless steel cookware may increase chromium
How is Chromium absorbed?
-Cr3+ is SOLUBLE in stomach and may bind to ligand;
-Absorbed throughout small intestine, especially JEJUNUM;
-Mode of absorption is hte usual suspects of diffusion or carrier-mediated transporter;
-~0.4% to 2.5% is ABSORBED for use by body
What enhances Chromium absorption?
1. Phenylalanine, methionine, histidine and other amino acids bind to chromium to keep it SOLUBLE in small intestine (Cr3+);
2. Picolinate also binds to chromium → chelating agent;
3. Vitamin C in one study ENHANCED absorption
What inhibits Chromium absorption?
-OLATION is process by which chromium binds with hydroxyl ions and then have polymerization and INSOLUBLE compound;
-Antacids and phytates also INHIBIT absorption
How is Chromium transported in the blood?
-In plasma Cr3+ COMPETES w/ IRON for transport on transferrin;
-If spots NOT available chromium binds to ALBUMIN;
-HIGH levels bind to globulins and lipoproteins
How is Chromium stored?
-Chromium is thought to be stored in TISSUES with FERRIC IRON because of transferrin transport
What are the functions of Chromium?
1. Chromium IMPROVES insulin signaling;
2. Chromium may also EHANCE insulin secretion;
3. Improvements in glucose tolerance and lipid profiles in people when chromium added to suboptimal chromium in diet;
4. Reports of improvement in body composition could not be substantiated;
5. Chromium may be necessary for integrity of nucleic acid strands, gives stability for mRNA synthesis by binding to the template strand
How does Chromium (Cr3)+ function as apart of CHROMODULIN for insulin regulation?
-Part of chromodulin in potentiating insulin’s reactions;
1. Transferrin delivers Cr3+ to tranferrin receptors (TfR) on cell membranes;
2. Cr3+ released inside cell;
3. Four Cr3+ complex with Chromodulin to form HOLOchromodulin or Cr4-Chromodulin;
4. Cr-Chromodulin increases kinase activity of the beta subunit of the insulin receptor and other cytosolic tyrosin kinases
What is Chromodulin?
-Chromodulin = aspartate, cysteine, glutamate, and glycine, bonded with four (Cr3+) centers;
-It interacts with the INSULIN RECEPTOR and has been confused with glucose tolerance factor.
What other nutrients doe Chromium interact with?
-High doses of chromium may cause problems with IRON transport;
-COMPETES for transferrin
How is Chromium excreted?
-Urinary chromium is 95% of excreted chromium;
-Diets high in simple sugars increase excretion of chromium in urine;
-Fecal chromium is UNABSORBED chromium
What are the recommendation for Chromium?
-Adult men = 35 µg
-Adult women = 25 µg
-No national survey data for chromium so used nutritionist-designed, well-balanced diets for recommendations
What is a Chromium deficiency?
-Impaired glucose tolerance
What results form a Chromium toxicity?
-Inorganic and organic forms available as SUPPS;
-Few serious adverse effects have been associated with excess intake of chromium from food so no UL was determined
How is Chromium status assessed?
-NO GOOD tests for chromium;
-Urinary chromium reflects recent intake and NOT STATUS
What are the sources of MANGANESE?
-Whole-grain cereals, dried fruits, nuts, and leafy vegetables are good sources;
-Processing grains REDUCES such that white flour is low in manganese
How is Manganese absorbed in the intestine?
-Mechanism of absorption is UNKNOWN;
-Absorption occurs throughout the small intestine;
-Rate of absorption <5%;
-Absorption is quickly saturable and probably involves low-capacity, high-affinity active transport mechanism, maybe like DMT1;
-High intakes lead to LOWER absorption to protect against toxicity → also with high intakes excretion increases;
-Believed that Mn2+ is absorbed
What factors affect the absorption of Manganese?
1. Histidine and citrate as ligands appear to ENHANCE absorption;
2. Studies suggest that fiber, phytate, and oxalate may PRECIPITATE manganese;
3. Iron may COMPETE with absorption if DMT1 is a common transporter;
4. Copper also decreases manganese absorption;
5. Vit C diminishes the Mn-dependent superoxide dismutase activity
How is Manganese transported in the Blood?
-In PORTAL BLOOD blood manganese is free or bound to α-2 macroglobulin
What happens to Manganese in the Liver?
Manganese LEAVES the LIVER free or bound to albumin, α-2 macroglobulin, β-globulin, or γ-globulin;
-IN the LIVER, manganese may be OXIDIZED by ceruloplasmin to Mn3+ and complexes to TRANSFERRIN (also carries chromium and iron) → bound to transferrin manganese is taken up by EXTRAHEPATIC tissues
How is Manganese stored?
-Manganese accumulates preferentially in the MITOCHONDROA of cells mediated by a calcium carrier;;
-Manganese does NOT concentrate in any particular tissue, but it is highest in bone, liver, pancreas, and kidneys
What is the function of Manganese?
1. Functions as an ENZYME ACTIVATOR and as part of METALLOPROTEINS;
-Manganese can bind to substrate OR to active site;
-But functions and deficiency NOT well correlated;
2. Also Involved in signal transduction by playing some role in increasing second messengers
Why is the function of Manganese and deficiency not correlated?
Activity of enzymes is generally NOT AFFEECTED by manganese deficiency for the most part;
-Other divalent cations like magnesium can replace the manganese;
-One exception to lack of specificity is with the GLYCOSYL TRANSFERASES
What are the enzyme classes that require Manganese?
1. Transferases (including kinases)
What are the Transferases?
Glycosyl transferases transfer sugars
What are the Hydrolases?
-Arginase is an example and is involved in urea synthesis in the liver;
-Prolidase is involved in collagen degradation
What are the Lysases?
-Phosphoenolpyruvate carboxykinase (PEPCK) is a lyase even though called kinase;
-Converts oxaloacetate to phosphoenolpyruvate important for gluconeogenesis
What are the Oxido-Reductases?
-Superoxide dismutase (SOD) in the mitochondria of cells is manganese-dependent;
-The zinc-copper SOD is extracellular and in the cytoplasm;
-MANGANESE-dependent SOD protects the MITOCHONDRIA from large amounts of superoxide radical products generated by electron transport
What are the Ligases/Synthetases?
-Pyruvate carboxylase that converts pyruvate to oxaloacetate;
-Glutamine synthetase is another example
What other nutrients does Manganese interact with?
-IRON and manganese have a RECIPROCAL relationship negatively affecting each other’s absorption when one is highly elevated → When one is high the other is less absorbed and vice versa;
-Possible DECREASED absorption of manganese can occur with calcium and zinc
How is Manganese excreted?
-Manganese is primarily excreted in the BILE;
-Excess is quickly excreted;
-Loss through sweat and skin desquamation can be significant
What are the recommendations for Manganese?
**AI for manganese:
-Adult men = 2.3 mg/day
-Adult women = 1.8 mg/day
-Based on the median intake from the FDA Total Diet Study
What is a deficiency of Manganese?
-To produce a deficiency it needs to be DELIBERATELY eliminated from the diet;
-Skeletal defects occur and lipid and carbohydrate metabolism are negatively affected
What is the UL for Manganese?
-UL for manganese = 11 mg/day;
-Based on neurotoxicity
How is Manganese status assessed?
-Plasma manganese may be a good marker, but DRI book states more work is needed;;
-Maybe mononuclear blood cells (means white blood cells)
What is Molybdenum?
-The need for molybdenum was established when genetic deficiencies in enzymes that require molybdenum as a cofactor resulted in severe pathology;
-Molybdenum is a METAL and found as either Mo4+ or Mo6+;
-IN our body, molybdenum is BOUND to either SULFUR or OXYGEN
What are the sources of Molybdenum?
-Molybdenum is widespread among foods, but the SOIL CONTENT is very important;
-Legumes, meat, fish and poultry are good sources;
-Grains and nuts and vegetables provide a good amount;
-But fruits and dairy products are especially LOW
How is Molybdenum absorbed?
-Absorption mechanism is thought to be PASSIVE, but site in GI tract is unknown;
-Absorption INCREASES over a very broad range of 22 to 1,490 µg/day (this seems unusual for a nutrient);
-50% to 90% is absorbed
How is Molybdenum transported in the blood?
-In BLOOD molybdenum is in the form of Molybdate (MnO42+);
-Appears to be transported by albumin or α-2 macroglobulin
How is Molybdenum stored?
-Liver, kidneys and bone contain the MOST molybdenum;
-Found in tissues as..
1. Molybdate → oxanion with Mo6+ (the highest oxidation state of molybdenum)
2. Molybdopterin (covered a related compound earlier) → Cofactors in molybdenum enzymes
4. Bound to enzymes
What are the functions of Molybdenum?
1. Molybdopterin catalyzes Redox-Rxns;
2. Aldehyde oxidase;
3. Xanthine dehydrogenase and xanthine oxidase;
4. May directly interact with the glucocorticoid receptor complex and INHIBIT its function
What genetic defect of Molybdenum can be LETHAL?
The INABILITY to synthesize molybdopterin because of genetic defects is usually LETHAL;
-Necessary for a series of enzymes that catalyze oxidation- reduction reactions
How does Molybdenum function with Xanthine dehydrogenase and xanthine oxidase?
-Enzymes play a role in degradation of pteridines, purines and pyrimidines, and other heterocyclic nitrogen-containing compounds;
-EX: the figure gives the example of hypoxanthine that is derived from purine catabolism → it is converted to xanthine and then uric acid;
-But the body can tolerate low function of these enzymes and excrete high levels of xanthine in urine with risk of increased kidney stones
How does Molybdenum function with Aldehyde oxidase?
Similar function to xanthine oxidase, but using aldehyde as substrate
What other nutrients does Molybdenum interact with?
1. Tungsten is a potent ANTAGONIST;
2. High dietary intake of sulfur or molybdenum can REDUCE tissue uptake of COPPER;
3. Copper and sulfate can affect molybdenum
-This has been shown particularly in RUNIMANTS;
-Mechanism is tetrathiomolybdates binding copper so it is NOT absorbed
-Tetrathimolybdates – a
How is Molybdenum excreted?
-Most molybdenum is excreted in the URINE;
-Amount in urine INCREASES with dietary intake;
-Kidney plays key role in molybdenum homeostasis
What are the recommendations for Molybdenum?
-RDA for molybdenum = 45 µg for adult men and women;
-Molybdenum balance studies were used to determine
What is a deficiency of Molybdenum?
-Main problem is Abnormal sulfur amino acid metabolism → neurological disorders occur with people with genetic deficiencies of sulfite oxidase;
-Deficiency is RARELY encountered unless diet is rich in antagonistic substances
What is the UL of Molybdenum?
UL = 2 mg/day based on impaired reproduction and growth in animals
How is Molybdenum assessed?
Blood levels are NOT used → Urinary output reflects intake
What is Fluoride?
-Fluorine is a GASEOUS element;
-Fluoride (F-) is BOUND to metals, nonmetals, or organic compounds;
-Fluoride in nature and in human body in TRACE amounts
What fluoride is found in water?
1. Drinking water fluoridated at 1 ppm (1 mg/L) since the 1950s;
-Discovered in 1942 that there was an inverse relationship b/w fluoride and dental caries;
2. Ready-to-use infant formulas are made with fluoridated water;
How is Fluoride found in foods?
The fluoride content in most FOODS is LOW;
-Some marine fish are relatively high in fluoride if the bones are consumed;
-Tea, both caffeinated and decaffeinated, are high in fluoride as tea leaves accumulate fluoride
How is Fluoride absorbed?
-Absorption is nearly 100% when it is consumed as..
1. Sodium fluorosilicate in fluoridated water or
2. Sodium fluoride or
3. Monofluorphosphate in toothpaste;
**Fluoride consumed with solid food or with calcium-containing beverages absorption DROPS into the range of 50 to 80%;
-Fluoride is also absorbed throughout the small intestine, but at a REDUCED RATE compared to the stomach
How is Fluoride transported in the blood?
-Fluoride is found in blood as ionic fluoride or as HF and as organic fluoride;
-Non-organic fluoride correlates with dietary intakes of fluoride, but organic fluoride does not
What are the functions of Fluoride?
-The major function of fluoride is related to MINERALIZATION of bones and teeth =
1. Fluoride replaces hydroxide ions in bones
2. Can replace calcium in formation of bone or can replace it in previously crystallized bone
3. Reduces cavities because fluorohydroxyapatiete in tooth enamel is less acid-sensitive than hydroxyapatite,
4. Topical fluoride appears to decrease acid production by oral plaque-producing bacteria
Where is Fluoride found in the body?
-Most fluoride is found in BONES and TEETH;
-Mineralized tissues account for ~99% of body fluoride with MOST IN BONE ;
-At HIGH absorption, the retained amount as percent becomes lower as the urinary excretion of fluoride increases;
-If the skeleton is growing greater amounts of fluoride are retained → Growing bones obviously need to retain more to foster more mineralization
What are the forms of Fluoride found BONE?
1. Amorphous state = Rapidly exchangeable pool;
2.Crystalline state = slowly exchangeable pool → the crystalline bone fluoride is part of APATITE
-Apatite – group of phosphate minerals, usually referring to hydroxylapatite, fluorapatite and chlorapatite, named for high
What is a deficiency of Fluoride?
There are a lot of data on dental caries, but very little data on the integrity of the skeleton;
-There are several reports on fluoride and the skeleton from 30 to 40 years ago
What is Fluorosis?
-Chronic TOXICITY of fluoride is called fluorosis and is characterized by changes in bone, kidney, and possibly nerve and muscle function;
-Dental fluorosis, which is also called mottling of teeth is a VISIBLE effect
What is the UL for Fluoride?
**UL INCREASES with age:
-UL for infants 0 to 6 months = 0.7 mg/day ;
-UL for children > 8 years of age and adults = 10 mg/day;
-UL was based on enamel and skeletal fluorosis;
**There is ACUTE toxicity that can lead to DEATH