400.WSVITAMINS & MINERALS

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jsohl
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146532
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400.WSVITAMINS & MINERALS
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2012-04-26 21:06:53
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minerals
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Nutritional Biochemistry. Water soluble vitamins & minerals
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  1. vitamin B1
    thiamin
  2. vitamin B2
    riboflavin
  3. vitamin B3
    niacin
  4. vitamin B5
    pantothenic acid
  5. vitamin B6
    pyridoxine
  6. vitamin B7
    biotin
  7. vitamin B9
    folate
  8. vitamin B12
    cobalamin
  9. Government mandates fortification with which B vitamins?
    1,2,3,9
  10. active form of thiamin
    • TPP - thiamin pyrophosphate
    • (B1)
    • cooking destroys it
  11. TPP functions
    • coenzyme for formation or degradation of alpha ketols by transketolase (ex. ribose in the PPP)
    • coenzyme for oxidative decarboxylation of alpha-keto acids (ex. pyruvate & alpha-ketoglutarate)
    • coenzyme for enzymes involved in biosynthesis of neurotransmitters
  12. PDH coenzymes
    • B1 - thiamin - TPP
    • B2 - riboflavin - FAD
    • B3 - niacin - NAD+
    • B5 - pantothenic acid - CoA
  13. thiamin deficiency
    • disruption of energy metabolism & neural functions
    • related to alcoholism blocking its absorption
    • Wernicke-Korsakoff Syndrome - alcohol-induced -apathy, confusion, memory loss, disrupted eye movements - IV or oral supplementation recommended
    • Beriberi - large refined / polished rice consumption - infantile: tachycardia, vomiting, convulsions, death / adult: dry skin, irritability, disordly thinking, progressive paralysis, muscle weakness, loss of appetite, depression, nerve degeneration, heart failure
  14. sources of thiamin
    • pork
    • legumes
    • nuts & seeds
    • (unstable during cooking)
  15. regulation for thiamin toxicity
    • absorption declines rapidly with increased consumption &
    • kidneys excrete it rapidly
  16. alchohol related deficiencies
    • thiamin (B1)
    • riboflavin (B2)
    • pryodoxine (B6) - rare
    • potassium
    • magnesium
  17. riboflavin
    • B2
    • heat-stable
    • yellow color
    • 2 active forms
    • part of 2 prosthetic groups - act as electron & hydrogen acceptors in redox rxns (Krebs cycle, beta-oxidation of FAs), rxns that remove ammonia during deamination of amino acids
    • flavin mononucleotide (FMN), prosthetic group of NADH dehydrogenase in ETC
    • flavin adenine dinucleotide (FAD), donates electrons & hydrogens to succinate dehydrogenase in ETC, prosthetic group of glutahione reductase (important for antioxidant activity of glutathione)
  18. glutahione reductase depends on...
    • FAD (riboflavin) as a prosthetic group
    • NADPH (niacin) so it can reduce peroxides
  19. sources of B2
    • (riboflavin)
    • milk, yogurt
    • bread products
    • 95% is bioavailable
  20. refined grain products are enriched with...
    • thiamin
    • riboflavin
    • niacin
    • folic acid
    • iron
  21. riboflavin deficiency
    • rare
    • associated with alcoholism & poor diet or long term use of barbiturate drugs that accelerate B2 metabolism/excretion
    • ariboflavinosis - shiny, inflamed tongue, corners of mouth cracked
    • overproduction of oil on scalp & in ears - seborrheic dermatitis - flakes
    • severe---anemia due to insufficient antioxidant defense
  22. riboflavin toxicity
    no cases
  23. niacin
    • B3
    • active forms are 2 pyridin derivatives: nicotinic acid & nicotinamide
    • part of 2 coenzymes: nicotinamide adenine dinucleotide (NAD+) & nicotinamide adenine dinucleotide phosphate (NADP+)
    • participates in redox rxns
    • NADH donates e-s to ETC
    • NADPH - for reductive synthesis, detox, and antioxidant rxns
  24. lactates conversion to pyruvate requires...
    NAD+ (niacin/B3)
  25. reducing peroxides in the body...
    • peroxide reduced to alchohol or water by glutathione peroxidase (containing Se) & GSH(reduced glutathione)
    • GSSG (oxidized glutathione) reduced by glutathione reductase (containing FAD+/riboflavin) and NADPH (niacin)
  26. sources of niacin
    • meat (liver), poultry, fish
    • enriched milk, grains, cereals
    • can be converted from tryptophan using riboflavin, B6 & Fe
  27. niacin deficiency
    • pellagra - redness around neck, roughened skin, dermatitis, diarrhea, dementia, death
    • a protein in corn tightly binds niacin, still fount in SE Asia & Africa
  28. niacin toxicity
    • treatment for hyperlipidemia (type IIb- high levels in of TAG/VLDL in blood)
    • flushing of face, arms, chest, itching, headaches, rash, nausea, glucose intolerance, blurred vision
    • sustained-relase supplements can be hepatoxic if taken for mo. or yrs.
  29. pantothenic acid
    • B5
    • heat sensitive
    • essential part of CoA which functions as an acyl group carrier (acetyl-CoA - TCA, ketone bodies, succinyl-CoA - TCA, fatty acyyl-CoA - FA synthesis)
    • component of ACP domain of fatty acid sythase (FAS)
  30. sources of panthotenic acid
    • widespread in all foods
    • freezing/canning/processing/refining decreases content
  31. B5 deficiency
    N/A
  32. B5 toxicity
    N/A
  33. pyrodoxine
    • B6
    • Pyrodoxil phosphate is the primary active coenzyme form.
    • pyrodoxil (PL), Pyrodoxine (PN), pyridoxamine (PM) are forms.
    • Forms from diet need to be dephosphorylated for absorption.
    • Coenzyme for reactions that transfer NH2 (transamination), COO-, COOH, H, & OH groups.
  34. coenzyme functions of B6
    • transamination
    • deamination
    • carboxylation
    • condensation
  35. pathways involving B6
    • blood cell formation -maintains health of thymus, spleen, lymph nodes; 1st step of heme synthesis (condensation of glycine + succinyl-CoA), regulates affinity of Hb for O2
    • carboyhdrate metabolism - utilization of aas in gluconeogenesis - transamination
    • lipid metabolism - coenzyme for sphingolipid synthesis, so effects formation of myelin sheaths through sphingomyelin
    • neurotransmitter synthesis - coenzyme for serotonin, GABA, dopamine, norepinephrine from aas
    • regualtion of blood homocysteine - PLP-dependent enzymes convert homocysteine to cysteine
    • helps convert tryptophan to B3
  36. What vitamins play a role in heme synthesis?
    • B6 - PLP is coenzyme for 1st step of heme synthesis (condensation of glycine + succinyl-CoA)
    • B5 - essential part of CoA - succinyl CoA is needed for 1st step in heme synthesis
  37. B vitamins and homocysteine levels
    • B6: PLP-dependent enzymes convert homocysteine to cysteine
    • B9/folate & B12 dependent enzymes convert homocysteine to methionine
    • asssociated with fatal CV events
    • low B6 or folate intake can result in high homocysteine levels
    • B12 can be stored, so that usually doesn't affect homocysteine levles
  38. sources of B6
    • fortified cereals, meat, fish, poultry
    • 75% bioavailable
    • heat destroys up to 50%
  39. B6 deficiency
    • rare, but alchoholism increases risk
    • TBC (tuberculosis) drug inactivates endogenous PLP
    • microcytic hypochromic anemia
    • seborrheic dermatitis
    • neurological symptoms -confusion, depression, convulsions
  40. causes of seborrheic dermatitis
    deficiency of PLP (B6) or riboflavin (B2)
  41. B6 toxicity
    nerve damage affecting walk
  42. biotin
    • B7
    • aka biosil, vitamin H, coenzyme R - necessary for bacterial growth
    • prosthetic group for carboxylases
    • carrier of activated carbon dioxide
  43. examples of biotin-dependent reactions
    • carboxylation of pyruvate to oxaloacetate in gluconeogenesis
    • elongation of FA chains
    • synthesis of ketone body acetoacetate
    • breakdown of aas iso, met, thr, val for entry into TCA
    • DNA synthesis
  44. souces of biotin
    • intestinal bacteria
    • cauliflower, liver, peanuts, cheese, egg yolk - cook eggs to prevent avidin in egg white from binding biotin
  45. biotin deficiency
    • anticonvulsive drugs
    • hairloss & rash...convulsion & neurological disorders
    • changes in blood pH...coma, death
  46. folate
    • B9
    • pteridine + para-aminobenzoic acid + glutamate
    • folic acid has only 1 glutamate molecule
    • folate usually has 3-11 molecules of glutmate which are removed (except for 1) in small intestine
    • active form = tetrahydrofolate (THFA) with 5 active forms / accept & donate 1C units (CH3) during synthesis of purine & pyrimidine bases used in DNA synthesis, cell division, amino acid synthesis, maturation of RBCs & other cells
  47. sources of folate
    • fortified cereals/grains
    • dark green veggies, OJ (vitamin C protects folate from oxidation),wheat germ, liver, sunflower seeds, legumes
    • vulnerable to heat
  48. folate deficiency
    • NTDs
    • megaloblastic anemia due to insufficient synthsis of purines and TMP (thymine monophosphate) needed for DNA, so cells can't divide
  49. cause of megaloblastic anemia
    • folate or B12 deficiency
    • RBC precursors in bone marrow can't form new DNA & divide
  50. folate can mask deficiency of...
    • B12
    • high folate can exacerbate neurological problems associated woth B12 deficiency for this reason
  51. folate toxicity
    hives & respiratory distress if person has a sensitivity
  52. B12
    • cabalamin
    • supplement form = cyanocobalamin - cotains Co
    • active forms in body = 5-deoxyadenosylcabalim & methylcobalamin
    • coenzyme for only 2 enzymes: methionine synthase (transfers CH3 from MTHF to help convert homocysteine to met ) & L-methylmalonyl-CoA mutase (last step in coversion of odd # FA from methylmalonyl CoA to Succinyl CoA for entry into TCA)
  53. sources of B12
    • microorganisms - can be obtained from animals
    • fortified cereals
    • ~50% bioavailable in foods
  54. absorption of dietary B12
    • binds to R protein (produced by salivary glands) in stomach
    • pancreatic proteases (trypsin) cleaves B12 from R protein
    • B12 binds to intrinsic factor (produced by parietal cells)
    • IF-B12 complex binds to brush border receptors in ileum & B12 is absorbed
    • B12 enters blood circulation bound to transcobalaminII (carrier protein)
    • B12 is delivered to liver, bone, developing blood cells
  55. factors decreasing B12 absorption
    • deficiency of R protein, pancreatic protease (trypsin), IF
    • transcobalamin II
    • removal of ileum or stomach
    • bacterial overgrowth in stomach
    • tapeworm
    • reduced acid in stomach
  56. B12 deficiency
    • due to impaired absorption since so much is stored in liver
    • rapidly dividing cells affected most
    • leads to MTHF accumulation & THF deficiency ---megaloblastic anemia
    • breakdown of myelin sheath causes neurological symptoms such as tingling, numbness in extremities, memory loss...
    • pernicious anemia - autoimmune disorder destroys parietal cells - loss of IF
    • nerve damage becomes fatal
    • B12 injections can reverse symptoms
  57. riboflavin and vitamin B6 deficiency can cause
    seborrheic dermatitis
  58. abnormal maturation of red blood cells
    • B6 deficiency (microcytic hypochromic anemia)
    • folate deficiency (megaloblastic)
    • B12 deficiency (megaloblastic)
  59. malabsorption of biotin (B7)
    from raw eggs
  60. impaired DNA synthesis
    folate (B9) deficiency
  61. synthesis of glucose from pyruvate in the pathway of gluconeogenesis requires
    B7 / biotin
  62. synthesis of nonessential amino acids in the transamination reactions requires
    B6 / PLP
  63. Microcytic hypochromic anemia associated with B6
    deficiency is caused by ____________ due to ________________.
    low hemoglobin production / impaired heme synthesis from amino acid precursors
  64. Ex. of vitamin-like compounds that are essential for cell function:
    • choline
    • carnitine
    • inositol
    • taurine
    • lipoic acid
  65. Binding of ___________ to ____________ is an
    essential step in muscle contraction
    Ca2+/troponin
  66. Which of the following is required for synthesis
    of ATP in a substrate-level phosphorylation reaction?
    Mg
  67. Binding of iron to the trans-acting iron
    regulatory proteins (IRPs) results in a __________ and in ______________.
    increased production of apoferritin

    decreased synthesis of transferin receptor (TfR)/ a decreased uptake of iron by cells

    • decreased binding of IRPs to the iron-responsive
    • elements (IREs)
  68. Zinc is stored in the cells bound to ___________
    in the molecule of _____________.
    cysteines/metallothionein
  69. Zinc deficiency can result in
    • night blindness
    • skin lesions and rashes
    • increased susceptibility to infections
  70. thioredoxin reductase
    reduction of dehydroascorbate
  71. selenocysteine
    • active form of Se
    • antioxidant protection via glutathione peroxidase
    • redox rxns - thioredoxin reductases (important for antioxidant protection & regulating cell growth & viability)
    • thyroid hormone metabolism / metabolism of Iodine
  72. Copper as _____________ plays an important role in ______________.
    a transition metal/ the electron transport in mitochondria
  73. Glutathione assists ________________ in reducing
    hydrogen peroxide.
    glutathione peroxidase
  74. Glutathione disulfide (GSSG) is ______________
    • produced during the reduction of H2O2 by glutathione peroxidase
    • a compound consisting of two glutathione molecules bound by a disulfide bridge
  75. a cofactor that helps glutathione peroxidase to reduce H2O2
    Se
  76. a coenzyme that helps glutathione reductase to reduce GSSG
    FAD+ / riboflavin / B2
  77. Thioredoxin reductase is a uses ________to reduce thioredoxin and other substrates.
    • NADPH
    • selenocysteine is a component of TRR
  78. Required for the oxidative decarboxylation of pyruvate
    • B5
    • TPP
    • nicotinic acid
  79. vitamin C functions
    • absorption of Fe in small intestine
    • coenzyme - formation & maintenance of connective tissue/collagen
    • antioxidant defense
  80. 2 biologically active forms of vitamin C
    • ascorbic acid
    • dehyroascorbic acid
  81. Most animals, but not humans, can synthesis what vitamin/mineral from glucose?
    vitamin C
  82. vitamin C's antioxidant roles
    • reducing agent - donates e-s to minimize free radical damage
    • helps recycle oxidized vitamin E
    • stabilizes reduced form of folate coenzyme
    • reduces nonheme iron Fe3+ to Fe2+ making it more bioavailable
  83. vitamin C's coenzyme roles
    • for enzymes catalyzing hydroxylation of prolyl & lysyl reisidues in collagen & elastin and hydroxylation of cholecaciferol to calcidiol in liver & calcitriol in kidneys
    • for enzymes invovled in synthesis of carnitine, neurotransmitters (norepinephrine, epinephrine, serotonin), thyroxine, steroid hormones, bile acids, purine bases
  84. hydroxylation of collagen fibers requires ________ & helps ____
    • vitamin C
    • add stability to triple helixes
  85. food sources of vitamin C
    • potatoes, citruis, tomoato, broccoli, strawberries, kiwi, cabbagee, spinach, green peppers
    • vulnerable to heat & oxygen
    • absoprtion decreases with increased intake
  86. vitamin C deficiency
    • scurvy - after 1 mo w/o vitamin C
    • collagen breakdown in connective tissue lead to loose teeth, bleeding gums & joints, swollen joints, hemorrhages around hair follicles on arms & legs
    • with prolonged deficiency: reopening of healed wounds, bone pain & fractures
    • diarrhea
    • depression
  87. vitamin C toxicity
    • N/A
    • may cause abdominal cramps, diarrhea, nausea, nosebleeds
    • excessive absorption of Fe & Fe induced oxidative damage
  88. choline
    • vitamin-like compound
    • supports structural integrity of cell membranes
    • needed for production of acetylcholine (neurotransmitter)
    • source of methyl groups for DNA methylation
  89. choline deficiency
    fatty liver
  90. carnitine
    • vitamin-like compound
    • synthesized from lysine in liver
    • carries FAs from cytosol into mitochondria for TCA cycle
  91. carnitine deficiency
    abnormal FA metabolism
  92. inositol
    • vitamin-like compound
    • synthesized from glucose
    • phospholipid in cell membrane
    • precursor to eicosanoids, hormone-like substances
    • regulates intracellular Ca++
  93. taurine
    • vitamin-like compound
    • involved in: photoreceptor activity in they eye, heart muscle contraction, insulin activity, cell growth, CNS functions & platelet aggregation
    • antioxidant in WBCs & lungs
  94. lipoic acid
    • vitamin-like compound
    • cofactor in energy-producing rxns in mitochondria (e.g. conversion of pyruvate to acetyl CoA)
    • antioxidant
  95. most essential nutrient
    water
  96. fluid compartments in body
    • Body Water
    • 2/3 - intracellular (cytoplasm & in organelles)
    • 1/3 - extracellular (plasma, interstitial fluid, lymph, CSF, etc.)
  97. Water's functions:
    • heat capacity - prevents overheating / freezing
    • cooling - perspiration
    • chemical reactions - solvent
    • pH balance
    • body fluids - transport, shock absorption, lubrication, cleansing
  98. electrolytes
    • Na+ - extracellular cation
    • K+ - intracellular cation
    • Cl- - extracellular anion
    • PO4 3- -intracellular anion
    • membrane pumps balance them
  99. Na/K pump
    3 Na+s out for every 2K+s in
  100. daily fluid intake & output
    • input: food, beverages, metabolism
    • output: kidneys/urine, insensible (skin, lungs, coughing, runny nose), feces
  101. hormonal regulation of water balance
    • osmoreceptors in hypthalamus sense high Na+ levels in blood
    • triggers thirst
    • pituitary gland secretes antidiuretic hormone (ADH), so kidneys reabsorb more water in proximal tubules of nephrons (inhibited by alcohol & caffeine)
    • blood volume increases / dilutes Na+
  102. response to low blood pressure
    • triggers thirst
    • kidneys sense & release renin, a protease
    • renin splits angiotensin I from angiotensinogen (in circulating plasma)
    • angiotensin I is converted to angiotensin II in lungs
    • angiotensin II (triggers thirst) is a vasoconstrictor (quick affect in minutes), it decreases Na+ & water excretion, and it induces adrenal glands to release aldosterone (long term control- hours/days)
    • aldosterone increases Na & water retention by kidneys
  103. dehydration
    • from diarrhea, vomitting
    • major killer
    • signs: fatigue, dry mouth, headache, dark urine, diminished physical & mental performance
    • IV or oral rehydration
  104. water intoxication
    hyponatremia
  105. major minerals
    • DRI > 100 mg/day
    • Ca
    • P
    • S
    • K
    • Na
    • Cl
  106. minor / trace minerals
    • DRI <100 mg/d
    • Mg
    • Fe
    • Zn
    • Cu
    • I
    • Mn
    • Se
  107. factors decreasing mineral bioavailability
    • phytate
    • polyphenols
    • oxalate
    • competition
    • high pH
    • decreased need
    • fiber
  108. sodium functions
    • extracellular cation
    • major mineral
    • works in concer with K+ & Cl-
    • regulation of extracellular fluid volume / blood pressure
    • nerve impulse transmission / muscle function
    • co-transport in small intestine (glucose uptake associated w/ Na/K pump)
  109. sources of sodium
    processed foods (soy sauce, picked foods, salty meats, cheeses, soups)
  110. hyponatremia
    • low blood sodium
    • caused by severe diarrhea, vomiting, sweating, overhydration, cancer, heart, kidney disease
    • symptoms resemble dehydration
    • swelling of cells - brain cell swelling: headache, confusion, seizures, coma..
  111. hypernatremia
    • associated w/ hypervolemia (increased blood volume); congestive heart failure/kidney failure
    • edema
    • HTN
    • normally functioning kidneys should correct the problem
    • can cause Ca loss in urine - osteoporosis
  112. salt sensitivity
    • common in obese / insulin-resistant individuals
    • African-Americans more sensitive
    • women more sensitive
    • aerobic exercise can decrease sodium sensitivity
  113. potassium functions
    • major intracellular cation
    • major mineral
    • works with Na+ to maintain membrane potential - nerve impulse transmission, muscle contraction, heart function
  114. sources of potassium
    fruits, veggies, grains (unprocessed)
  115. hypokalemia
    • low blood potassium
    • caused by losses through prolonged vomiting, chronic diarrhea, laxative abuse, some diuretics, alcoholism, bulimia
    • muscle weakness & cramps, loss of appetite, confusion, disrupted heart rhythms
  116. hyperkalemia
    • high blood potassium
    • malfunctioning kidneys, excessive oral or IV K+ administration
    • never just diet alone because normally kidneys remove excess
    • can slow or stop heart (used in lethal injections)
  117. Potassium for lowering disease risk
    • decreased risk of stroke
    • increased bone mineral density
    • decreased (Ca++) kidney stone formation
  118. calcium
    • most abundant mineral in human body (major mineral)
    • bone & teeth structure (w/ phosphate base in hydroxyappetite)
    • blood clotting cascade - to form fibrin (works with vitamin K)
    • nerve impulse transmission & muscle contraction (voltage dependent Ca channels)
    • metabolism of macronutrients (insulin secretion by beta cells, cofactor for calmodulin-containing enzymes in glycogenolysis - attaches to glycogen phosphorylase kinase after vitamin K, involved in muscle contraction)
    • may reduce risk of HTN, obesity, colon & breast cancer
  119. Ca & muscle contraction
    • Ca is normally pumped back into sarcoplasmic reticulum during muscle relaxation.
    • when nerve signal triggers opening of Ca channels, Ca rushes out & binds to troponin which triggers muscle contraction
  120. sources of calcium
    • dairy, greens (but oxalae decreases absorption), fish w/ bones, sesame seeds, tofu
    • calcium citrate is absorbed best
    • inorganic Ca interferes with iron absorption
    • excess Ca can interfere w/ abosrption of some other minerals & meds (tetracycline)
    • 25-75% is absorbed from diet
  121. factors affecting absorption rate of caclium
    • 25-75% absorbed
    • age - decreases with age except for pregnancy
    • vitamin D intake increases it
    • Ca intake (higher decreases absorption)
    • phytate, oxalate
    • estrogen levels (lower levels lower absorption because estrogen regulates transcription of PTH which activates vitamin D in kidneys)
  122. Ca & P role in bone structure
    • OSTEOBLASTS:
    • secrete collagen matrix
    • deposit Ca & P around collagen
    • hydroxyapatite
    • peak bone mass ~ age 30
    • strengthened with weight-bearing exercise
    • OSTEOCLASTS:
    • resorb bone & release Ca & P into blood to maintain blood Ca level
  123. Hormonal Regulation of Blood Calcium
    • calcitriol: active vitamin D
    • PTH: increases Ca absorption & reabsorption through transcriptional of transporters & bone resorption
    • calcitonin: bone formation (thryroid)
  124. hypocalcemia
    • low blood calcium
    • cause = kidney failure, PT disorders, vitamin D deficiency
    • signs = muscle spasms, facial grimacing, convulsions
    • osteoporosis
  125. hypercalcemia
    • high blood calcium
    • cause = cancer & overproduction of PTH
    • signs = fatigue, confusion, loss of appetite, constipation
    • deposits in soft tissue, imparing function (vitamin D toxicity)
    • extreme: coma, cardiac arrest
  126. calcium deficiency
    due to abnormal PT function, vitamin D deficiency, kidney failure, Mg deficiency (osteoclasts less responsive), high Na intake (more excretion in urine), high protein intake (more excretion in urine), caffeine (more excretion in urine)
  127. chloride
    • major extracellular anion
    • mainly in CSF & GI excretions
    • also in plasma & intersitial fluid
    • FUNCTIONS:
    • HCI in stomach (kills bacteria & denatures proteins)
    • fluide balance (cell and organelle membrae potential maintained through bidirectional chloride channels)
    • hypochlorous acid (COCl-) immune cells kill bacteria
    • assists resabsorption of K+ in kidney
    • helps transmit nerve impulses
  128. sources of chloride
    • table salt
    • processed foods
  129. hypochloremia
    • low blood chloride
    • frequent vomiting (bulimia)
    • can lead to metabolic alkalosis (high blood pH, potenially fatal)
    • signs: abnormal heart rhythm, decreased blood flow to brain, abnormal metabolism
  130. hyperchloremia
    • high blood chloride
    • acidosis in blood
    • rare but can be caused by diarrhea (when bicarbonate is lost, kidney reabsorbs Cl- to replace lost anion), certain kidney diseases, overactive PT
  131. phosphorus
    • most abundant intracellular anion
    • PO3 3-
    • FUNCTIONS:
    • bone structure (part of hydroxyapatite mineal complex)
    • phospholipids (membranes & lipoproteins)
    • phosphorylated compounds: ATP, P-creatine, nucleotides, hormones, hormone receptors, signaling molecules, enzyme regulation, buffer of intracellular environment (can accept/donate electrons), 2,3-bisphosphoglycerate which decreases O2 binding to Hb
  132. intake of dietary phosphorus
    • ABSORPTION:
    • 55-70% - modulated by body's needs
    • excess is excreted by kidneys
    • PTH / calcitriol (vitamin D) enhance intestinal absorption of phosphorus through transcriptional upregulation of transporters, but we usually get an excess
    • EXCRETION:
    • high plasma PO4 inhibits calcitriol formation in kidney; PTH/calcitriol cause rapid loss of phosphours in urine
    • high fructose intake results in negative PO4 balance though loss in urine & uncontrolled synthesis of F-1-P
  133. sources of phosphorus
    • meat, milk, eggs
    • processed foods have phosphate salts
    • seeds/beans, but can't be absorbed well due to phytate
  134. hypophosphatemia
    • low blood phosphorus
    • rarely due to dietary deficiency
    • hyperparathyroidism, vitamin D deficiency may affect absorption or excretion
    • overuse of aluminam antacids - bind phosphorus
    • alchoholism - malnutrution
    • symptoms: anorexia, dizziness, bone pain, muscle weakness, waddling gait
  135. hyperposphatemia
    • high blood phosphate
    • kidney disease, underactive PT gland, excess vitamin D supplements
    • excess phosphorus can bind Ca and lead to muscle spasms/convulsions
    • excess intake w/ insufficient Ca can lead to bone loss
  136. magnesium
    • Mg
    • major mineral
    • cofactor for enzymes involved in phosphorylation rxns (ATP , GTP, CTP synthesis --stabilizes structure), DNA RNA, lipid, carb, protein, synthesis, glutathione synthesis for antioxidant protection.
    • stabilizes nucleotides in DNA/chromosomes - transcription, RNA & ribosomes - translation, crosslinks between proteins & phospholipids in membranes
    • ion transport in muscle cells (heart contraction), neural transmission
  137. Mg deficiency
    • rare
    • bone stores keep cell & body fluid levels constant
  138. sources of Mg
    • whole grains, veggies, legumes, nuts, tofu, seafood
    • hard tap water
    • processing severely decreases Mg
    • 50% is absorbed
    • Ca supplements can interfere w/ absorption
  139. hypomagnesemia
    • magnesium deficiency
    • usually occurs w/ K & P deficiencies since the minerals are found together
    • caused by GI, kidney disease, chronic alcoholism, excessive use of diuretic drugs
    • absorption decreases with age
    • gradual loss of appetite, nausea, weakness
    • eventually muscle cramps, confusion, abnormal heart rhythm, death
  140. hypermagnesemia
    • high blood magnesium
    • caused by kidney disease, Mg-containing laxatives & antacids
    • symptoms: nausea due to fall in bp, general weakness
    • high does IV used to stop premature labor; can cause diarrhea/GI disturbance
  141. Mg for disease treatment
    • doses higher than UL
    • HTN ?
    • Preeclampsia-eclampsia
    • MI?
    • DM - may lower fasting plasma glucose
    • migraine - reduces frequency by increasing intracellular levels
    • asthma -
  142. sulfur
    • major mineral
    • doesn't function as a free atom or ion
    • component of: aas (met, cys), glycosphingolipids (sulfatides), sulfated aminosugars (chondroitin sulfate & glucoseamine sulfate in cartilage & can be absorbed from supplements), biotin, thiamin
    • glutathione (GSH) - tripeptide with cysteine - antioxidant, component of hepatic phase II detox system
    • disulfide bridges - tertiary structure of proteins, S atoms in cys bind w/ each other
  143. sources of S
    • protein rich foods: eggs, dairy, meat, fish, legumes, odiferous veggies
    • deficiency only if soil or intestinal bacteria is low
    • low oral toxicity
  144. HTN reduction
    • lower Na
    • decrease obesity
    • increase Ca
    • increase Mg
    • increase K
  145. Osteoporosis & minerals
    associated with low Ca, P, Mg
  146. iron
    • Fe
    • trace / micromineral
    • transition metal
    • mostly absorbed in Fe2+ (divalent / ferrous) iron as opposed to Fe3+ (trivalent / ferric) iron
    • redox rxns
    • can bind reversibly to O, N, S
    • promotes formation of free radicals
  147. functions of Fe
    • oxygen transport & storage - Hb - represents ~2/3 of body's Fe; myoglobin transports O2 inside muscle cells
    • electron transport & energy metabolism - cyt b, c, c1, a, a3 in ETC; cytochrome 450, heme containing hepatic enzymes involved in oxidative metabolism of many endogenous compounds, catalyze detox of drugs & pollutants; nonheme Fe enzymes such as succinate dehydrogenase in TCA cycle
    • antioxidant & immune function - catalase, hemeprotein that reduces H2O2 to water & O; Fe superoxide dismutase reduces superoxide radical to H2O2 (in plants & bacteria only); myeloperoxidase, hemeprotein that synthesizes hypochlorous acid (bleach)form Cl- & H2O2 in monocytes to kill bacteria
  148. monocytes use what to kill bacteria?
    • hypochlorous acid (bleach) produced by myeloperoxide (a heme protein)
    • requires Fe for heme protein, Cl- & H2O2
  149. regulation of Fe in the body
    • Body balances absorption, transport, storage & losses, but no regulation through excretion
    • absorption decreases when Fe stores are sufficient
    • ~ 6% absorption (woment of child-bearing age ~13%)
    • storage: ferritin (soluble - found in most cells) storage form in intestinal cells (Cu containing ceruloplasmin oxidizes Fe2+ for this) ; hemosiderin (insoluble - associated w/ pathogens - tends to be irreversible binding)
    • transport: transferrin, plasma protein, transports Fe from intestinal cells to organs; accepted into cells through receptor -mediated endocytosis w/ transferrin
    • 70% of iron in body is bound to functional compounds hemoglobin, myoglobin, heme & nonheme enzymes
  150. factors affecting Fe absorption
    • GI function: gastric acid helps solubilize & convert Fe3+ to Fe2+; declines with age; viamin C; organic acids
    • heme iron is absorbed better than nonheme (in plants)
    • phytate, fiber, soy, Ca, P, tannins, polyphenols, oxalate, & Zn inhibit
  151. Iron Turnover & loss
    • RBC formation & destruction
    • lost in feces & sloughed mucousal & skin cells
    • menstruation
    • GI issues: IBD, bowel cancer, hookworm infection
  152. transcriptional regulation of Fe homeostasis
    • Tfr mRNA has IREs at 3' end - IREs bind to trans-acting IRP when Fe level is low, so mRNA is stabilized & TfR is synthesized, when FE level is high, IRP binds to it, releasing IREs & TfR mRNA is degrated
    • apoferretin has IREs at 5' end, so IRPs bind to IRE when Fe levels are low, and apoferritin transcription is blocked, so excess won't be stored; when Fe levels are high, apoferretin mRNA is transcribed, so it can be stored, lowering levels
  153. sources of Fe
    • seafood, red meat, poultry
    • fortified cereals
    • tofu, legumes
    • consume veggies w/ vitamin C rich foods to maximize bioavailability
  154. Fe deficiency
    • most common nutritional deficiency
    • most prevalent in 6-24 mo. old children
    • anemia - fatigue, rapid HR, palpitations, rapid breathing
  155. Stages of Iron Deficiency
    • DEPLETION OF FE STORES: decreased ferretin
    • DEPLETION OF FUNCTIONAL FE: hemoglobin/myoglobin, decreased transferrin saturation, increased erythrocyte protoporphyrin, decreased physcial performance
    • IRON-DEFICIENCY ANEMIA: decreased Hb, Hct, RBC size (microcytic hypochromic anemia), cognitive impairment, poor growth, decreased performance, decreased exercise tolerance
  156. microcytic hypochromic anemia
    • pyrodoxil (B6) deficiency - needed for heme synthesis or
    • Fe deficiency
  157. Fe toxicity
    • OD from supplements - nausea, vomiting, diarrhea, rapid heartbeat, confusion, death
    • chronic excessive intake - may increase risk of CVD, cancer, T2DM, neurodegenerative disease
  158. hereditary hematochromatosis
    • genetic defect causing excessive Fe absorption
    • organ damage due to buildup
    • increased risk of CVD, DM, cirrhosis, liver cancer, arthritis
    • Tx: minimize Fe intake, phlebotomy
  159. zinc
    • trace/micromineral
    • transition metal - 2 oxidation states: Zn1+ or ZN2+ - divalent is found in stable chemical compounds
    • no redox changes under physiological conditions
    • high affinity for thiols; forms Zn2+ thiolate clusters
    • enzyme structure & function, gene regulation
  160. functions of Zn
    • cell replication
    • fertility & reproduction
    • hormone activity
    • sexual maturation
    • night vision
    • immune function
    • Hb activity
    • lipid metabolism
    • protein metabolism
    • gene expression
    • cell growth
    • cell replication
  161. functions of zinc
    • enzyme cofactor - active structure and/or catalyticaly active; antioxidant enzyme Cu/Zn-superoxide dismutase; RNA polymerases I, II, III; alcohol dehydrogenase
    • structural role - cell membrane; protein tertiary structure
    • regulatory role - Zn-finger proteins as transcription factors that initiate gene expression, cell signaling & nerve transmission, hormone release, regulation of apoptosis (supplementation inhibits apoptosis)
    • immune system
    • vision: required for enzyme conversion of retinol to retinal & synthesis of retinol binding protein (RBP) in liver
  162. Zinc absorption
    • 10-35% absorbed
    • stimulated by deficiency
    • small amounts absorbed more effectively
    • inhibited by phytate (& Ca) , fiber, nonheme Fe due to competition for transporters
    • binds to divalent metal binding protein in intestinal cells
    • bound to albumin & alpha2-macroglobulin in blood
    • 90% of body's zinc is in muscle & bone, part bound to metallothionein (MT)
  163. Zn transport & distribution
    • bound to albumin & alpha2macroglobulin in blood
    • in muscle & bone, part bound to metallothionein (MT)
    • Zn induces MT expression
    • MT expression mediated by metal-binding transcription factor (MTF-1) & metal response element (MRE)
    • intestinal cell recycle Zn from digestive enzymes
  164. Metallathione (MT)
    • cysteine-rich protein that binds heavy metals (Zn, Cu, Ni, Cd)
    • can bind up to 7 Zn2+s (3 in beta domain & 4 in alpha domain)
    • Zn from beta domain is available for intracellular metabolism because it is not as stable
    • Zn from alpha domain may be involved in detox of excess Zn
  165. sources of Zn
    • protein rich foods: dark meat, seafood, oysters, clams, wheat bran (but poorly absorbed ue to phytate & fiber)
    • dairy, grains
  166. Zn deficiency
    • common in populations subsiting on cereal grains
    • caused by diarrhea & chronic infections, malabsorption, increased losses (sickle cell anemia, diabetes, renal disease)
    • can cause: impaired growth & sexual maturation, acne, pregnancy complications, susceptibility to infections
    • can lead to: skin lesions, rashes, hair loss, loss of appetite, night blindess, infections
  167. acrodermatits enteropathica
    • mutation of gene encoding for Zn transporter in small intestine
    • slowing of growth & development, delayed maturation, skin rashes, chronic & severe diarrhea
    • oral Zn therapy
  168. Zn toxicity
    • acute is rare but can be caused by galvanized containers
    • GI problems
    • chronic toxicity from supplements: increased LDL, decreased immune function, inhibition of Cu absorption - used to treat Wilson disease (hyperabsorption & accumulation of Cu)
  169. selenium
    • ultratrace/micromineral
    • highly toxic semi-metal / metalloid
    • reacts with thiols (like metals)
    • can replace S in amino acids cys & met
    • found mainly as selenocysteine & selenomethionine as part of selenoproteins
    • selenocysteine is the active form
  170. selenocysteine
    • 21st aa
    • can also be synthesized from serine during translation & inserted at UGA codon
  171. functions of Se
    • component of glutathione peroxidases, antioxidant enzymes that break down peroxide
    • metabolism of I - component of iodothyrodine deiodinases (ID-I, ID-II, & ID-III) involved in metabolism of iodine & the thryoid hormone
    • needed for three thrioredoxin reductases (TRR 1, 2, 3) that reduce disulfide bridges in thioredoxin (for antioxidant protection & cell growth) and in vitamin C
  172. hypothyroidism
    severity increased by iodine & selenium deficiencies
  173. absorption of Se
    • vitamins A, C, E & reduced glutathione enhance absorption
    • phytates & heavy metals inhibit
    • excess excreted in urine & feces
    • high dose ingestion of inorganic Se results in volatile methylated metabolites where are excreted in breath & skin
  174. sources of Se
    organ meats, seafood (but not good source of Se-aas), grains
  175. Se deficiency
    • Keshan disease - (viral) cardiomyopathy in China - little Se in soil
    • chronic total parenteral nutrition
  176. Se toxicity
    • inorganic Se is toxic
    • brittle hair & nails / hair loss
  177. iodine
    • ultratrace / micromineral
    • non-metallic
    • iodide - anion
    • erosion depletes I
  178. functions of I
    • component of thyroid hormones: triiodothyronine (T3) & thyroxine (T4 - 95%)
    • T3 is the biologically active form
    • regulates body temperature, BMR, reproduction, growth
  179. I absorption & metabolism
    • 100% bioavailable
    • in the thyroid gland it is attached to thyroglobulin, the storage form of thyroid hormones
    • TSH from pituitary signals thyroid to cleave T3 & T4 from thyroglobulin
    • selenoenzymes (iodiothyronine deiodases I, II, & III) convert T4 to T3
    • kidneys excrete excess I
  180. sources of I
    • seafood
    • added to salt & cattle feed
  181. I deficiency
    • raw cabbage, turnips, rutabagas, cassavas are goitrogens - block absorption of metabolism of I
    • goiter due to continuous TSH production
    • gestational brain development problems
  182. I toxicity
    • inhibited synthesis of thyroid hormones
    • inhibition by substrate (I)
    • goiter
  183. copper
    • trace / micromineral
    • transition metal Cu+1, Cu+2
    • Cu+2 is main form in body
    • redox rxns, scavenges free radicals
  184. copper's functions
    • antioxidant enxymes - Cu/Zn-superoxide dismutase reduces superoxide radical (Cu in catalytic center & Zn has tertiary structure role)
    • electron carriers in ETC (last electron acceptor, cytochrom oxidase, a3)
    • component of ceruloplasm which oxidizes ferrous (Fe2+) to ferric (Fe3+) for incorporation into transferrin
  185. Cu absorption & metabolism
    • ~50% absorbed
    • amino acids (esp histidine) enhance absorption
    • Fe, Zn, phytates inhibit absorption
    • albumin transports for intestine to liver where 2/3 is incorporated into ceruloplasmin
    • excess excreted in feces & urine
  186. sources of Cu
    organ meats, shellfish, nuts, seeds, legumes, chocolate
  187. Cu deficiency
    • preterm infants - defective iron mobilization - anemia, bone abnormalities
    • Menke's syndrome - occipital horn syndrome - genetic deficiency in Cu transporter regulating tissue distribution; Cu accumulates in intestine, muscle, spleen, kidney; neurological degeneration, hypotonia, kinked hair, abnormal connective tissue, osteoporosis, poor growth
  188. Cu toxicity
    • Wilson's disease - genetic - impaired Cu excretion in bile; manifests in adolescence, accumulates in tissues; liver (swelling), brain, kidneys, eyes, RBCs, Kayser-Fleischer ring in eye
    • chelation therapy or Zn or Mo supplementation
  189. Manganese
    • Mn
    • toxic heavy metal
    • ultratrace mineral
    • concentrated primarily in bone, liver, pancreas, brain
    • cofactor for Mn-superoxide dismutase in mitochondria, arginase to help form urea, pyruvate carboxylase to convert pyruvate to oxaloacetate in gluconeogenesis, cartilage / collagen
  190. Mn absorption & metabolism
    • poor absorption to protect against toxicity
    • transferrin binds it & transports it
    • excretion regulates levels
    • bile is main excretory route
    • no storage
  191. Mn sources
    cereals, nuts, tea, some fruits
  192. Mn deficiency
    • nontrauma epilepsy, PKU, ALS, MS may increase marginal risk of deficiency
    • may impair CHO & fat metabolism & growth
  193. Mn toxicity
    occupational exposures only
  194. fluoride
    • ultratrace / micromineral anion
    • bones & teeth contain most
    • stimulates mineralization - reacts with hydroxyapatite to form fluoroapatite
  195. Fl absorption & excretion
    • ~100% absorption in water
    • 50-80% absorption in food
    • excess excreted in urine
  196. Fl deficiency
    dental caries, bone integrity hampered
  197. Fl toxicity
    • fluorsis
    • acute toxicity - from hemodialysis pts - nausea, abnormal heart rhythm, fractures
  198. chromium
    • ultratrace / micromineral - very toxic heavy metal
    • Cr3+ (most common) & Cr6+ (carcinogenic)
    • enhances insulin's effects - helps stimulate GLUT4 by LMWCr (low molecular weight) binding to receptor
  199. Cr absorption
    • inorganic is low; organic (ex. Cr-picolinate) is 10-25%
    • enhanced by need, vitamin C, aspirin (organic acids)
    • inhibited by antacids
    • transferrin & albumin transport Cr in blood
    • excreted in urine
  200. tranferrin transports
    • Fe, Cr, Mn
    • in blood
  201. albumin transports
    • Cu, Cr, Zn
    • in blood
  202. sources of Cr
    brewer's yeast, beer, processed meats, whole grains, green beans, broccoli, spices, stainless steel dishes
  203. Cr deficiency
    • difficult to assess
    • decreased insulin-mediated glucose uptade - elevated blood glucose & insulin
    • blood lipid abnormalities
  204. Cr toxicity
    no dietary cases
  205. molybdenum
    • Mo
    • ultratrace element
    • in 3 enzymes found in liver for sulfite -->sulfates, breakdown of nucleotides produce H2O2, hyroxylation of endogenous compounds, drugs, toxins
  206. Mo absorption
    • 80-90%
    • rapid excretion in urine & bile
    • dietary Cu can inhibit Mo absorption
  207. Mo sources
    peas, beans, cereals, organ meats
  208. Mo deficiency
    TPN or genetic disorder - weakness, confusion, night blindness
  209. Mo toxicity
    high intake inhibits Cu absorption - treatment for Wilson's disease
  210. Ultratrace minerals
    • ultratrace minerals <1 mg/d
    • Cr, Fl, I, Mn, Mo, Se

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