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113 Cards in this Set
- Front
- Back
Heme- Iron: Structure
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Porphyrin Ring-Ferrous Iron (Fe 2+)
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Heme-Iron Absorption Rate
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30%
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Heme-Iron dietary Sources
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Animal Products
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Non-heme structure
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Fe(3+)-Food
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Non-heme Iron dietary sources
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Plant foods and dairy products
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Non-Heme absorption Rate
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10%
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Ferritin
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Intracellular iron storage protein
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Transferrin
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Protein which transports iron through blood
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Transferrin Receptor
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Carrier protein for transferrin, necessary to import iron into cell
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Hemochromatosis
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Hereditary disease that cause an increased iron absorption and inappropriate deposition in heart, liver and pancreas
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HCP
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Heme iron carrier. Carries heme, separated from dietary proteins into enterocytes through receptor mediated transport
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Heme Oxygenase
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Hydrolyzes porphyrin ring in enerocytes to release ferrous iron (Fe2+)
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Ferrous Iron
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Fe2+
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Ferric Iron
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Fe3+
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Duodenal Cytochrome B (DcytB)
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Reduces non heme (ferric iron 3+) iron to Ferrous iron (2+) in the small intestines for absorption
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DMT1
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transporter in enterocytes that absorbs iron
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Ferroportin
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transmembrane protein that exports iron out of cells
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Hephaestin
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Transmembrane Cu-dependent ferroxidase that is needed to export iron out of enterocytes into circulation. Catalyzes the reaction of ferrous (2+) into Ferric (3+) for transport.
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Ceruplasmin
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Cu-carying ferroxidase in the blood that is involved in iron metabolism. Oxidizes ferrous iron (Fe2+) into ferric iron (Fe3+) so that it can bind to transferrin and be exported out of cell
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Hepcidin
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Peptide hormone secreted by the liver that senses Fe stores and downregulates ferroportin expression in enterocytes
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Transport Form of Iron
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Ferric Iron (3+)
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Absorbed Form of Iron
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Ferrous Iron (2+)
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Storage Form of Iron
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Hepatocytes, ferritin
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Digestion and Absorption of Heme Iron
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Found as myoglobin or hemoglobin , hydrolyzed to form porphyrin ring and heme then absorbed by HCP1
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Digestion and Absorption of non-heme iron
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Non-heme iron bound to food is hydroxylized by proteases releasing reduced Ferrous (2+) with the aid of Duodenal Cytochrome B (DcytB). Then is transported into the cell by DMT1
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Iron's fate
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1. Circulation to aid in other tissues
2. Stored or eliminated 3. Used by intestinal Cells |
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Release of Iron from Enterocyte for transport
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Ferrous (Fe2+) binds to ferroportin to be released from enterocyte but before it is transported it is oxidized back into Ferric (Fe3+) by hephaestin then bound to transferrin for transport
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Iron Absorption enhancers
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Acids, meat, fish, poutry, Mucin (chelates iron), Fe deficiency*
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Iron Absorption Inhibitors
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Ca2+ Zn2+ Mn2+ Ni2+ which compete for transport
Ca, oxalates, phytates, tannins cause precipitation out of cell Physiological states: Low HCl, rapid transit time, good iron status |
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What is iron always bound to for transport
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transferrin
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What state is iron needed to be in to bind and what is needed to help this
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Ferric state, Cu-carrier ceruloplasmin
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Iron Overload storage problems
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Stores as hemosiderin which makes iron not accessible
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Hepcidin
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Peptide hormone that senses Fe status "News reporter"
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Where is hepcidin secreted from and what gene regulates it
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Liver; HFE gene
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Hepcidin Function
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Inhibits ferroportin expression
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What happens when the body is iron defficient
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- hepcidin, +ferroportin expression, + export of iron out of cells
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What happens when the body is in iron overload
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+hepcidin, -ferroportin expression, - export of iron out of cells
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In what three ways is iron homeostasis maintained
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Absorption
Transport in/out of cells by transferrin Storage within cells |
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4 Functions of Iron
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1. Oxygen delivery
2. Immune function (myloperoxidase, bleach to kill microorganisms) 3. AOX (catalase) 4. VC requiring enzymes |
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Osteoporosis
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Calcium deficiency disease where structural deteriation occurs and bone density is reduced to the point of being porous
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Parathyroid horomone function
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+ bone resorption
+ kidney reabsorption (+ hydroxylase to activate Vitamin D) + Intestinal absorption (+calbindin) |
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Calcitonin
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Hormone secreted from the thyroid gland in response to hypercalcemia
- PTH release - Bone resorption |
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Paracellular Transport
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A form of Ca transport that occurs when calcium concentration in the ileum and colon are high enought cause passive diffusion of calcium between the enterocytes
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What are the functions of calcium
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structural (bone/teeth), blood clotting, intracellular signaling (muscle contraction, nerve conduction, membrane permeability, cellular differentiation and proliferation, gene expression, secretion and exocytosis, cell death, energy metabolism)
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Non nutritional causes of hypercalcemia
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hyperparathyroidism, malignancy
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Hypocalcemia
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hypoparathyroidism, parathyroid hormone resistance, liver and renal disease
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Calcium abundance level
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most abundant divalent cation
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Calcium Dietary Sources
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Milk, dairy, some seafoods
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Calcium Digestion
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Present as insoluable salts, released before absorption which is stabolized by high stomach pH
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Calcium Absorption
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Calcium binds to calbindin for transport into enterocytes.
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What induces the synthesis of calbindin?
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calcitriol
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What calcium-binding proteins facillitate the transport of calcium in enterocytes?
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calcitriol and calmodulin
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What is the Absorption process of calcium that is saturable?
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Energy requiring, requires CBP or calbindin and is stimulated by calcitriol
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Low calcium levels
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+ calbindin (CBP)
+Cacitriol + PTH |
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Calcium Transport out of enterocyte
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Requires Ca2+ Mg2+ ATPase, which hydrolyzes the release of energy to pump Ca out of the cell as Mg moves in, stimulated by vitamin D
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Paracellular transport of calcium
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Passive diffusion in the small intestines, when calcium levels are high which opens the junctions between cells to facilitate absorption
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Paracellular transport
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between cells instead of through them
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What enhances paracellular absorption for calcium
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Fructose oligosaccharides, insulin and nondigestable saccharides
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Calcium absorption in the large intestines
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binds to pectins
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Enhancing calcium absorption
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lactose, sugars, sugar alcohols and protein
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Calcium inhibitors
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Phytate, oxalate *spinach, rhubarb, swiss cheese, berries, nuts, tea, Mg, zinc, fatty acids
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Calcium transport forms
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Bound to proteins (albumin and prealbumin), complexed with sulfate, phosphate or citrate, or free Ca
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Where does PTH selectively increase calcium reabsorption in the kidney
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+ 1-hydroxylase + calcidiol + vitamin D
Increased vitamin D increases calbindin + Ca reabsortion |
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What fluid compartment is magnesium most abundant
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intracellular fluid
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What tissue contains 60% of our body pool of magnesium
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bone
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What are some enzymes that require Mg
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Kinases (stabilizes P, creatine kinase), transketolase, alpha-KGDH, RNA/DNA polymerases, ion channel regulation (ATPase), cAMP formation (ATP-> cAMP)
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What is magnesium mainly found intracellularly?
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Negatively charged molecules, P
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High Doses of Mg...
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more active transport
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Low does of Mg...
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more passive transport
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List some pathways Mg is involved in
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Energy production, anabolic pathways
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What organ regulates Mg homeostasis
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Kidneys
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What are some functions of Mn
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Metabolism, bone development, AOX, Stepping in for Mg functions (energy production, anabolic pathways, DNA synthesis)
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In what cellular compartment does Mn exert antioxidant activity? and as what?
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Mitochondria, As MnSOD
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What divalent cation may substitute for Mn in some reactions
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Mg
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How does Mn interact with iron
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Fe inhibits Mn absorption
Mn absorption increases during Fe deficiency High Fe stores associated with low Mn absorption |
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What about chromium deficiency leads one to believe that it is involved in glucose homeostasis?
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Because high chromium levels are associated with
+ insulin and glucose + TAG +TC -HDL |
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What is the proposed mechanism regarding the role of chromium in modulating insulin sensitivity?
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Increased insulin receptor activity increases glucose intake into cells. Cr taken into cells by transferrin bind to apo-chromodulin to form holochromodulin which binds to insulin receptor and stimulates tyrosine kinase activity of the receptor, enhancing P-ations resulting in an increase in GLUT transporters to cell surface, improving insulin responsiveness
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How common is Mn deficiency
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rare
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What is the major transport protein for copper, what is the lesser transport protein
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ceruloplasmin, albumin
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What functions does ceruplasmin have?
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transport protein for copper, uptake of Cu into cells, oxidizes ferrous iron into ferric iron so that it can bind to transferrin and be transported out of cells
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What would happen to erythropoiesis if ceruplasmin activity diminished
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Microcytic hypchronic anemia due to the ceruloplasm's need to help iron get transported out of cells
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What enzyme is homologous to ceruplasmin?
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Duodenal Cytochrome B
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What would happen to iron status if ceruplasmin activity was was inhibited
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Ferric iron would be unable to be reduced to ferrous iron and thus unable to be absorbed
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What are the functions of copper
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iron metabolism, energy production, collagen formation, norepinephrine production, Melanin Production, AOX functions, Gene expression
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What deficiency symptoms are characteristic of impaired iron metabolism?
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Anemia
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What deficiency symptoms are characteristic of impaired energy production?
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Weakness, fatigue
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What deficiency symptoms are characteristic of impaired collagen formation?
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impaired wound healing, tooth loss, low vascular integrity, laxity in joints
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What deficiency symptoms are characteristic of impaired norepinephrine production?
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genetic disorders, diminished intellect
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What deficiency symptoms are characteristic of impaired melanin production?
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hypopigmentation
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What deficiency symptoms are characteristic of impaired AOX function?
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Impaired AOX production
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What is metallothionein?
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a protein expressed by every cell in the body. In enterocytes it sequesters cu
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Why would zinc supplementation be useful in copper overload, what role does MT play in this?
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Zn increases MT expression causing less Cu to transported into circulation
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Why does copper defiency result in anemia
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Cu is a part of ferroxidases whitch proper iron utilization is dependent on
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What protein binds copper and zinc intracellularly
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Metallothionein
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What is bone remodeling?
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Coupled process of bone resorption and formation
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Osteoclasts
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erosion of bone surfaces through enzymes
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Osteoblasts
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From stromal cells, produce new bone material
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Osteocytes
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Mechanoreceptors in bone signal for OC and OB
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Stromal Cells
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Produce growth factor for hematoposesis, stimulate oc's to form, differentiate themselves into OB's
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Briefly describe the main mode of transport in the circulation for cholecalciferol
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bound to DBP in circulation to take to extrahepatic tissue and has an affinity for calcitriol and calcidiol
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In what less frequent way is D transported throughout the body?
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In chylomicrons
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Name the vitamin D responsive tissues and describe the responses in those tissues
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Bone= +resorption
Kidneys= +reabsorption Intestines= +absorption |
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What condition initiates vitamin D responses in tissues and what other hormone is required?
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Low blood calcium, PTH
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If a child were born with a genetic defect in their VDR, what would be the clinical outcome you might expect?
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Rickets
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If we were unable to fully activate vitamin D, what would you expect parathyroid levels to do and why?
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+ PTH
Due to inability to activate vitamin D in low blood calcium levels |
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What are the functions of vitamin D?
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Regulates Ca & P homeostasis, cell differentiation, eliminates proliferation of epithelial cells, hormone acitivites
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What are good sources of vitamin D?
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Sunlight, gish, milk, cereal, Oj, egg yolks, mushroom
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Cholecalciferol
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Inactive vitamin D
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Calcidiol
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Form used to evaluate vitamin D status, hydroxylated by the liver
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Calcitriol
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Hormone form of vitamin D
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Calbindin
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Vitamin D dependent Ca binding protein in enterocytes that is necessary for moving calcium out of enterocytes into the blood
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Rickets
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Vitamin D deficiency, failure of bone mineralization
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Osteomalacia
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In adults: VD deficiency, deformities of long bones, spine, ribs, failure of re mineralization of bone
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