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113 Cards in this Set

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