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Iron locations in the body:
65% in __________
20% in __________
10% in __________
5% in _________
Hemoglobin
Blood & Storage
Myoglobin
Cofactor for enzymes
Why are women more likely to be deficient in Iron?
Store lot less than men & heavy cycles
What is the source of non-heme iron vs heme iron?
Non-heme = plants/supplements
Heme = animal products
In what form is non-heme iron found? Heme iron?
Non = salt form
Heme = part of hemoglobin, myoglobin, and heme enzymes
Which kind of iron is absorbed by facilitated diffusion using heme carrier protein 1, with Fe2+ being released inside the enterocyte by heme oxygenase, and needs to be bound to ferritin because its toxic?
Heme Iron
Which kind of iron is absorbed using generic divalent mineral transporter, using proteases to remove protein and ferrireductase to reduce ferric to ferrous (2+) which then gets absorbed by facilitated diffusion?
Non-heme iron
T/F: Heme iron requires Vitamin C for absorption
FALSE
Non-heme requires vitamin C (ferrireductase)
What are 6 factors that can decrease Fe absorption?
1) Polyphenols (coffee/tea)
2) Phytate (whole grains, legumes, nuts, seeds)
3) Oxalate (spinach, tea, veggies, chocolate)
4) Phosvitin (egg yolk)
5) Ca, Zn, Mn, Ni
6) Acid reducing meds (H2 receptor blocker and protein pump inhibitor)
What are 4 factors that can increase Fe absorption?
1) Fructose and sorbitol
2) Acids (ascorbic, citric, lactic, tartaric)
3) Meat, poultry, fish
4) Mucin
Which iron binding protein functions in iron stores? Where is it located (4)?
Ferritin
Location: SI, liver, spleen, bone marrow
What iron binding protein functions in transporting Fe across the basolateral membrane? Where is it located? What mineral does it require?
Ferroprotein
Located: Si
Requires Cu
What iron-binding protein transports Fe in the plasma? Where is it located?
Transferrin
Located: Plasma
What are the 4 locations of iron stores?
1) SI
2) Liver
3) Spleen
4) Bone marrow
What is the peptide hormone produced by the liver to regulate iron absorption?
Hepcidin
Synthesis of Hepcidin is mediated by liver iron levels, with ______ iron leading to more hepcidin made, inflammation and infection leading to _________ hepcidin made, and hypoxia & anemia leading to _________ hepcidin made?
High
More
Less
What is the RDA for Iron?
Men = 8
Nonpreg women = 18
Pregnant women = 27
Vegetarians = 1.8x RDA
What are 9 sources of dietary iron?
1) Liver/organ meat
2) Seafood
3) Lean meat
4) Poultry
5) Legumes
6) Veggies
7) Black strap molasses
8) Dried fruit
9) Whole grain & enriched bread
What are the most common sources of iron in the US? (9)
1) Fortified cereal
2) Bread
3) Cakes
4) Donuts
5) Cookies
6) Pasta
7) Beef
8) Dried beans
9) Poultry
What are the 3 major functions of Iron?
1) Oxygen transport (part of heme)
2) Metabolism (cofactor for cytochromes, synthesis of DNA, collagen/purine, catalase)
3) Catalase (AOX)
What two enzymes require iron as a cofactor?
Catalase & Myeloperoxidase
What are 5 signs/symptoms of iron deficiency?
1) Pallor
2) Fatigue
3) Decreased cognition
4) Short attention span
5) Depressed immune system
What type of anemia may be found in iron deficient patients?
Hypochromic microcytic anemia
What are 5 possible causes of iron deficiency?
1) Low intake
2) Excessive blood loss
3) Achlorhydria (older patients)
4) Consumption of binders (vegan diet)
5) GI lesions decreasing absorption
What are 5 symptoms of iron toxicity?
1) Iron supplements decrease Zn absorption
2) Organ damage
3) GI bleeding
4) Shock
5) Metabolic acidosis
What three populations should not take Iron supplements?
1) Alcoholics
2) Postmenopausal women
3) Older males
What is a genetic condition with increase in iron to toxic levels that can cause death, so must "blood let" or give blood routinely?
Hemochromatosis
How is Zinc mostly found? How is it digested?
Found mostly divalent molecule
Digested using proteases & nucleases
Absorption of Zinc occurs through a combination of what 3 mechanisms?
1) Diffusing using ZIP4 carrier
2) Diffusing using DMT (divalent mineral trans)
3) Paracellular absorption
What are 2 things that enhance zinc absorption?
1) Proteins (bind S & N)
2) Acids
What are 3 inhibitors of zinc absorption?
1) Binders (polyphenols, phytate, oxalate)
2) Iron & Copper
3) Acid reducing meds (H2 receptor blockers; proton pump inhibitors)
What is the short-term storage form of Zinc found in the liver, pancreas, kidneys, intestines, keratinocytes, & RBCs?
Metallothionein
Zinc is a part of metalloenzymes, and plays a function in what 7 major enzymes/actions?
1. alkaline phosphatase
2. carboxypeptidase & aminopeptidase
3. heme synthesis
4. Superoxide dismutase (antioxidant)
5. Phospholipase C (cell signaling)
6. Polyglutamate hydrolase (folate digestion)
7. Matrix metalloproteinases (protein recycling)
Folate contains many glutamic acid residues which are removed by what enzyme that involves Zinc?
Polyglutamate hydrolase
What are the two superoxide dismutase (SOD) enzymes that involve Zinc? What other mineral do they involve?
SOD1 & 3
Copper
SOD1 is located in the _________, while SOD3 is located in the __________.
Cytosol
Extra-cellular
What are 6 other functions of zinc, other than enzymatic activity?
1. Gene expression (Zn fingers)
2. Insulin release
3. Membrane stabilization
4. Immune function
5. Sexual maturation
6. Fertility/reproduction
What is Zinc's effect on the immune system?
Important for immune system
(ex: take 75-80 mg/d w/in 24 hours of cold to decrease duration/severity of cold)
BUT: too much can be immunosuppressive
Zinc, along with Vitamin C, Vitamin E, and B-carotene is involved with decreasing age-related what?
Macular degeneration
What enzyme is zinc involved with that allows the conversion of Vitamin A forms (Retinol --> Retinal --> Retinoic acid)?
Alcohol dehydrogenase
Without zinc, what happens to vitamin A?
Stuck in liver due to lack of transport (RBP)
Excessive Zinc (toxicity) can lead to a decrease in absorption of what two minerals, leading to their deficiencies?
Copper & Calcium
What are 5 sources of Zinc?
1) Seafood (OYSTERS)
2) Meat
3) Legumes
4) Dairy
5) Fortified cereals
What are some symptoms of Zinc deficiency in kids?
slow growth, skeletal abnormalities, poor wound healing, diarrhea, dermatitis, delayed sexual maturation
What are some symptoms of Zinc deficiency in adults?
anorexia, diarrhea, depression, dermatitis, hypogeusia (lack of taste), alopecia, vision, problems, impaired immune function, wound healing
What is a genetic condition causing decreased Zn absorption (deficiency), leading to terrible skin lesions that are easily infected?
Acrodermatitis enteropathica
Who is at risk for zinc deficiency (6)?
1. Malabsorption
2. Alcoholics
3. Vegetarians
4. Older patients
5. Those w/ limited incomes
6. Sickle cell anemia
What are some symptoms of a Zn toxicity?
anemia, fever, metallic taste, headache, nausea, vomiting, bloody diarrhea, neurological issues (numbness, weakness, ataxia of gait)
What are the 5 major functions of Copper?
1) Iron transport (ceruloplasmin/ferroxidase)
2) Metabolism of superoxide, CA, 5-HT
3) Synthesis of ATP (cytochrome C in ETC; metalloenzyme)
4) Cross-linking of collagen
5) Tyrosinase
What enzyme is involved in the cross-linking of collagen function for Copper?
Lysyl oxidase
What enzyme is involved in melanin synthesis for Copper?
Tyrosinase
What two antioxidant enzymes is copper involved with? What other mineral is involved?
SOD 1 (cytoplasm) & 3 (extracellular)
Zinc
What other vitamin assists copper in the dopamine to norepinephrine conversion?
Ascorbic acid (Vit C)
What is used when the body needs iron, to transport it out across the basolateral membrane, from the enterocyte to the lumen?
Ceruloplasmin (ferroxidase)
What are the 6 dietary sources of Copper?
1) Liver
2) Oyster
3) Nut/seeds
4) Legumes
5) Cocoa
6) Meat
What are some risks of copper deficiency? (3)
Antacids
Zn, Fe, Ca supplements
Malabsorptive conditions
What are 4 symptoms of copper deficiency? Which symptoms is the best early indicator?
1) Anemia
2) Depigmentation of skin & hair
3) Bone demineralization
4) Neutropenia (impaired immunity; Best early indicator)
What are 5 symptoms of copper toxicity?
1) Nausea/vomiting
2) Gastric pain
3) Liver damage (jaundice)
4) Kidney damage
5) Free radical production (pro-oxidant)
What genetic condition is due to copper malabsorption & excessive urinary loss, due to deficiency?
Menkes Syndrome
What genetic condition is causing impaired copper excretion leading to toxicity which accumulates in liver, brain, kidneys, & eyes with Kayser Fleischer rings around the cornea, with symptoms seen >7 years of age?
Wilson's disease
What are the 2 major functions of Iodine?
1) Thyroid hormones (synthesis of T4 & T3)
2) Fetal development (skeleton & CNS)
What are the 4 major dietary sources of Iodine? Which is the major source in the US?
1) Iodized salt
2) Seafood
3) Dairy (major source in US)
4) Fruits/veggies (depends on soil)
What are proteins in food that bind iodine, prohibiting absorption, found in cabbage, kale, soy, peanuts, cassava, cauliflower, and is inactivated by cooking?
Goitrogens
What are 5 symptoms of Iodine deficiency/toxicity?
1) Goiter (low T4 --> secrete TSH --> hyperplasia)
2) Cretinism (in utero)
3) Congenital hypothyroidism (genetic defect)
4) Impaired mental/physical development, decreased IQ, and delayed growth/sexual maturation
5) Hypothyroidism (decreased metabolism, weight gain, coarse hair, cold intolerance)
What mineral can replace magnesium when necessary?
Manganese
What is the major function of Manganese? (3)
Cofactor for
1) SOD2 = mitochondria
2) Synthesis of bone, cartilage, and connective tissue (wound healing)
3) Superoxide dismutase (SOD) & clearance of radical (AOX)
What are 6 dietary sources of Manganese?
Shellfish
Whole grains
Legumes
Nuts
Coffee/Tea
What are the symptoms of a manganese deficiency?
Decreased reproductive/growth, skeletal abnormalities
What are the risks for manganese toxicity?
Miners inhaling Mn dust or patients w/ liver failure
What are some symptoms of Manganese Toxicity? (7)
Liver/brain damage
Neurological abnormalities
Tremors
Memory impairment
Insomnia
Anxiety
Headache
What is the major funciton of Molybdenum?
Cofactor
What enzyme is Mo a cofactor for and is involved in the conversion of hypoxanthine to uric acid, purine metabolism, and gout?
Xanthine oxidase
What does uric acid accumulation cause?
Gout
What are dietary sources of Mo?
Legumes
Whole grains
Dairy
Organ meats
What are the signs/symptoms of Mo deficiency?
Encephalopathy & seizures
What are the signs/symptoms of Mo toxicity?
Gout
<2% of what mineral is absorbed?
Chromium
What are the 3 functions of Chromium?
1) Glucose tolerance factor (GTF)
2) Insulin secretion/binding
3) Macronutrient metabolism
What are 4 good dietary sources of Chromium?
1) meats
2) whole grains
3) juices
4) yeasts
What are 2 poor sources of Chromium?
1) dairy
2) fruits/veggies
What are the 3 main symptoms of a Chromium deficiency?
1) weight loss
2) peripheral neuropathy
3) elevated plasma glucose & FFA
What are the 3 functions of Selenium?
1) Cofactor (selenoproteins)
2) Glutathoine peroxidase (AOX)
3) Removal of peroxynitrite radical by selenoprotein P (AOX)
What is the cofactor function of Selenium involved in? (2)
1) Reproduction & DNA synthesis
2) Converts T4 to T3
What enzyme needs selenium and is found in the plasma, cytoplasm, and mitochondria of cells and is important for converting H2O2 into water, and is a great AOX enzyme?
Glutathione peroxidase
What are the dietary sources for Selenium? (4) What is Selenium highly dependent on?
1) Brazil nuts
2) Seafood
3) Meat
4) Whole grains
Highly dependent on soil content
What selenium deficiency condition is cardiomyopathy in children and women, with necrosis of the heart?
Keshan's disease
What selenium deficiency is chronic degeneration and necrosis of joints of the legs and arms?
Kashin-Becks disease
What are some general symptoms of Selenium deficiency? (4)
Poor growth
Muscle pain
Depigmentation of hair/skin
Whitening of nail beds
What are 8 symptoms of Selenium toxicity?
1) garlicky breath
2) Hair/nail brittleness
3) skin leasions
4) Nausea & diarrhea
5) fatigue
6) irritability
7) muslce cramps
8) Inhibition of protein synthesis
What is meant by a U-shaped curve w/ Selenium and Cancer risk?
Low serum Se concentrations inversely related to heart disease and some cancers
Selenium supplementation increases risk of cancer, diabetes, HTN
With any form of supplementation, there are health limitations on both sides of the curve
What is the major function of Fluoride?
Prevent dental caries (cavities)
To prevent dental caries, Fluoride will facilitate the crystallization of calcium and phosphorus as __________, promote repair and remineralization, reverse ________ process, and decrease the growth of _______________ in the mouth
Fluorapatite
Decay
Microorganisms
Crystallization of what two minerals will create fluorapatite? Why is it better than hydroxyapatite?
Calcium & Phosphorus
More acid-resistant!
What are 5 sources of Fluoride?
1) Fluoridates water
2) Fluoridated toothpaste
3) tea
4) grape juice/raisins
5) crab/shrimp
What are the signs of a Fluoride deficiency?
Dental caries
What are the 2 chronic signs of a fluoride toxicity (Fluorosis)?
Mottling of teeth & pitting of bones
What are the 4 acute signs of Fluoride Toxicity (Fluorosis)
Nausea/Vomiting
Diarrhea
Hearth arrhythmias
Death
What are the 4 functions of body water?
1) Solvent
2) Transport
3) Thermoregulation
4) Lubricant
What are the 3 compartments that body water are found in?
1) ECT-Plasma (4% infants, adult males, adult females)
2) ECT - Interstitial fluid (26% infant, 16% adult male, 11% adult female)
3) ICT (45% infant, 40% adult male, 35% adult female)
What are 6 variables that change water requirements?
1) Environment (increased body temp increases loss)
2) Activity level (sweat & increased metabolism)
3) Functional losses (diarrhea or excessive urination)
4) Metabolism (1mL per Cal)
5) Age (highest requirement in infancy)
6) Caffeine
What population has the highest water requirement?
Infancy