400.WSVITAMINS & MINERALS

thiamin

riboflavin

niacin

pantothenic acid

pyridoxine

biotin

folate

cobalamin

1,2,3,9

• TPP - thiamin pyrophosphate
• (B1)
• cooking destroys it

• 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

• B1 - thiamin - TPP
• B2 - riboflavin - FAD
• B3 - niacin - NAD+
• B5 - pantothenic acid - CoA

• 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

• pork
• legumes
• nuts & seeds
• (unstable during cooking)

• absorption declines rapidly with increased consumption &
• kidneys excrete it rapidly

• thiamin (B1)
• riboflavin (B2)
• pryodoxine (B6) - rare
• potassium
• magnesium

• 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)

• FAD (riboflavin) as a prosthetic group
• NADPH (niacin) so it can reduce peroxides

• (riboflavin)
• milk, yogurt
• bread products
• 95% is bioavailable

• thiamin
• riboflavin
• niacin
• folic acid
• iron

• 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

no cases

• 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

NAD+ (niacin/B3)

• 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)

• meat (liver), poultry, fish
• enriched milk, grains, cereals
• can be converted from tryptophan using riboflavin, B6 & Fe

• pellagra - redness around neck, roughened skin, dermatitis, diarrhea, dementia, death
• a protein in corn tightly binds niacin, still fount in SE Asia & Africa

• 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.

• 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)

• widespread in all foods
• freezing/canning/processing/refining decreases content

N/A

N/A

• 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.

• transamination
• deamination
• carboxylation
• condensation

• 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

• 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

• 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

• fortified cereals, meat, fish, poultry
• 75% bioavailable
• heat destroys up to 50%

• rare, but alchoholism increases risk
• TBC (tuberculosis) drug inactivates endogenous PLP
• microcytic hypochromic anemia
• seborrheic dermatitis
• neurological symptoms -confusion, depression, convulsions

deficiency of PLP (B6) or riboflavin (B2)

nerve damage affecting walk

• B7
• aka biosil, vitamin H, coenzyme R - necessary for bacterial growth
• prosthetic group for carboxylases
• carrier of activated carbon dioxide

• 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

• intestinal bacteria
• cauliflower, liver, peanuts, cheese, egg yolk - cook eggs to prevent avidin in egg white from binding biotin

• anticonvulsive drugs
• hairloss & rash...convulsion & neurological disorders
• changes in blood pH...coma, death

• 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

• fortified cereals/grains
• dark green veggies, OJ (vitamin C protects folate from oxidation),wheat germ, liver, sunflower seeds, legumes
• vulnerable to heat

• NTDs
• megaloblastic anemia due to insufficient synthsis of purines and TMP (thymine monophosphate) needed for DNA, so cells can't divide

• folate or B12 deficiency
• RBC precursors in bone marrow can't form new DNA & divide

• B12
• high folate can exacerbate neurological problems associated woth B12 deficiency for this reason

hives & respiratory distress if person has a sensitivity

• 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)

• microorganisms - can be obtained from animals
• fortified cereals
• ~50% bioavailable in foods

• 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

• deficiency of R protein, pancreatic protease (trypsin), IF
• transcobalamin II
• removal of ileum or stomach
• bacterial overgrowth in stomach
• tapeworm
• reduced acid in stomach

• 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

seborrheic dermatitis

• B6 deficiency (microcytic hypochromic anemia)
• folate deficiency (megaloblastic)
• B12 deficiency (megaloblastic)

from raw eggs

folate (B9) deficiency

B7 / biotin

B6 / PLP

low hemoglobin production / impaired heme synthesis from amino acid precursors

• choline
• carnitine
• inositol
• taurine
• lipoic acid

Ca2+/troponin

Mg

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)

cysteines/metallothionein

• night blindness
• skin lesions and rashes
• increased susceptibility to infections

reduction of dehydroascorbate

• 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

a transition metal/ the electron transport in mitochondria

glutathione peroxidase

• produced during the reduction of H2O2 by glutathione peroxidase
• a compound consisting of two glutathione molecules bound by a disulfide bridge

Se

FAD+ / riboflavin / B2

• NADPH
• selenocysteine is a component of TRR

• B5
• TPP
• nicotinic acid

• absorption of Fe in small intestine
• coenzyme - formation & maintenance of connective tissue/collagen
• antioxidant defense

• ascorbic acid
• dehyroascorbic acid

vitamin C

• 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

• 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

• vitamin C
• add stability to triple helixes

• potatoes, citruis, tomoato, broccoli, strawberries, kiwi, cabbagee, spinach, green peppers
• vulnerable to heat & oxygen
• absoprtion decreases with increased intake

• 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

• N/A
• may cause abdominal cramps, diarrhea, nausea, nosebleeds
• excessive absorption of Fe & Fe induced oxidative damage

• vitamin-like compound
• supports structural integrity of cell membranes
• needed for production of acetylcholine (neurotransmitter)
• source of methyl groups for DNA methylation

fatty liver

• vitamin-like compound
• synthesized from lysine in liver
• carries FAs from cytosol into mitochondria for TCA cycle

abnormal FA metabolism

• vitamin-like compound
• synthesized from glucose
• phospholipid in cell membrane
• precursor to eicosanoids, hormone-like substances
• regulates intracellular Ca++

• 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

• vitamin-like compound
• cofactor in energy-producing rxns in mitochondria (e.g. conversion of pyruvate to acetyl CoA)
• antioxidant

water

• Body Water
• 2/3 - intracellular (cytoplasm & in organelles)
• 1/3 - extracellular (plasma, interstitial fluid, lymph, CSF, etc.)

• heat capacity - prevents overheating / freezing
• cooling - perspiration
• chemical reactions - solvent
• pH balance
• body fluids - transport, shock absorption, lubrication, cleansing

• Na+ - extracellular cation
• K+ - intracellular cation
• Cl- - extracellular anion
• PO4 3- -intracellular anion
• membrane pumps balance them

3 Na+s out for every 2K+s in

• input: food, beverages, metabolism
• output: kidneys/urine, insensible (skin, lungs, coughing, runny nose), feces

• 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+

• 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

• from diarrhea, vomitting
• major killer
• signs: fatigue, dry mouth, headache, dark urine, diminished physical & mental performance
• IV or oral rehydration

hyponatremia

• DRI > 100 mg/day
• Ca
• P
• S
• K
• Na
• Cl

• DRI <100 mg/d
• Mg
• Fe
• Zn
• Cu
• I
• Mn
• Se

• phytate
• polyphenols
• oxalate
• competition
• high pH
• decreased need
• fiber

• 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)

processed foods (soy sauce, picked foods, salty meats, cheeses, soups)

• 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..

• 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

• common in obese / insulin-resistant individuals
• African-Americans more sensitive
• women more sensitive
• aerobic exercise can decrease sodium sensitivity

• major intracellular cation
• major mineral
• works with Na+ to maintain membrane potential - nerve impulse transmission, muscle contraction, heart function

fruits, veggies, grains (unprocessed)

• 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

• 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)

• decreased risk of stroke
• increased bone mineral density
• decreased (Ca++) kidney stone formation

• 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

• 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

• 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

• 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)

• 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

• calcitriol: active vitamin D
• PTH: increases Ca absorption & reabsorption through transcriptional of transporters & bone resorption
• calcitonin: bone formation (thryroid)

• low blood calcium
• cause = kidney failure, PT disorders, vitamin D deficiency
• signs = muscle spasms, facial grimacing, convulsions
• osteoporosis

• 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

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)

• 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

• table salt
• processed foods

• 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

• 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

• 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

• 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

• meat, milk, eggs
• processed foods have phosphate salts
• seeds/beans, but can't be absorbed well due to phytate

• 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

• 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

• 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

• rare
• bone stores keep cell & body fluid levels constant

• whole grains, veggies, legumes, nuts, tofu, seafood
• hard tap water
• processing severely decreases Mg
• 50% is absorbed
• Ca supplements can interfere w/ absorption

• 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

• 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

• doses higher than UL
• HTN ?
• Preeclampsia-eclampsia
• MI?
• DM - may lower fasting plasma glucose
• migraine - reduces frequency by increasing intracellular levels
• asthma -

• 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

• protein rich foods: eggs, dairy, meat, fish, legumes, odiferous veggies
• deficiency only if soil or intestinal bacteria is low
• low oral toxicity

• lower Na
• decrease obesity
• increase Ca
• increase Mg
• increase K

associated with low Ca, P, Mg

• 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

• 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

• hypochlorous acid (bleach) produced by myeloperoxide (a heme protein)
• requires Fe for heme protein, Cl- & H2O2

• 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

• 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

• RBC formation & destruction
• lost in feces & sloughed mucousal & skin cells
• menstruation
• GI issues: IBD, bowel cancer, hookworm infection

• 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

• seafood, red meat, poultry
• fortified cereals
• tofu, legumes
• consume veggies w/ vitamin C rich foods to maximize bioavailability

• most common nutritional deficiency
• most prevalent in 6-24 mo. old children
• anemia - fatigue, rapid HR, palpitations, rapid breathing

• 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

• pyrodoxil (B6) deficiency - needed for heme synthesis or
• Fe deficiency

• OD from supplements - nausea, vomiting, diarrhea, rapid heartbeat, confusion, death
• chronic excessive intake - may increase risk of CVD, cancer, T2DM, neurodegenerative disease

• 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

• 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

• cell replication
• fertility & reproduction
• hormone activity
• sexual maturation
• night vision
• immune function
• Hb activity
• lipid metabolism
• protein metabolism
• gene expression
• cell growth
• cell replication

• 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

• 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)

• 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

• 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

• protein rich foods: dark meat, seafood, oysters, clams, wheat bran (but poorly absorbed ue to phytate & fiber)
• dairy, grains

• 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

• mutation of gene encoding for Zn transporter in small intestine
• slowing of growth & development, delayed maturation, skin rashes, chronic & severe diarrhea
• oral Zn therapy

• 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)

• 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

• 21st aa
• can also be synthesized from serine during translation & inserted at UGA codon

• 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

severity increased by iodine & selenium deficiencies

• 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

organ meats, seafood (but not good source of Se-aas), grains

• Keshan disease - (viral) cardiomyopathy in China - little Se in soil
• chronic total parenteral nutrition

• inorganic Se is toxic
• brittle hair & nails / hair loss

• ultratrace / micromineral
• non-metallic
• iodide - anion
• erosion depletes I

• component of thyroid hormones: triiodothyronine (T3) & thyroxine (T4 - 95%)
• T3 is the biologically active form
• regulates body temperature, BMR, reproduction, growth

• 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

• seafood
• added to salt & cattle feed

• raw cabbage, turnips, rutabagas, cassavas are goitrogens - block absorption of metabolism of I
• goiter due to continuous TSH production
• gestational brain development problems

• inhibited synthesis of thyroid hormones
• inhibition by substrate (I)
• goiter

• trace / micromineral
• transition metal Cu+1, Cu+2
• Cu+2 is main form in body
• redox rxns, scavenges free radicals

• 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

• ~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

organ meats, shellfish, nuts, seeds, legumes, chocolate

• 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

• 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

• 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

• poor absorption to protect against toxicity
• transferrin binds it & transports it
• excretion regulates levels
• bile is main excretory route
• no storage

cereals, nuts, tea, some fruits

• nontrauma epilepsy, PKU, ALS, MS may increase marginal risk of deficiency
• may impair CHO & fat metabolism & growth

occupational exposures only

• ultratrace / micromineral anion
• bones & teeth contain most
• stimulates mineralization - reacts with hydroxyapatite to form fluoroapatite

• ~100% absorption in water
• 50-80% absorption in food
• excess excreted in urine

dental caries, bone integrity hampered

• fluorsis
• acute toxicity - from hemodialysis pts - nausea, abnormal heart rhythm, fractures

• 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

• 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

• Fe, Cr, Mn
• in blood

• Cu, Cr, Zn
• in blood

brewer's yeast, beer, processed meats, whole grains, green beans, broccoli, spices, stainless steel dishes

• difficult to assess
• decreased insulin-mediated glucose uptade - elevated blood glucose & insulin
• blood lipid abnormalities

no dietary cases

• Mo
• ultratrace element
• in 3 enzymes found in liver for sulfite -->sulfates, breakdown of nucleotides produce H2O2, hyroxylation of endogenous compounds, drugs, toxins

• 80-90%
• rapid excretion in urine & bile
• dietary Cu can inhibit Mo absorption

peas, beans, cereals, organ meats

TPN or genetic disorder - weakness, confusion, night blindness

high intake inhibits Cu absorption - treatment for Wilson's disease

• ultratrace minerals <1 mg/d
• Cr, Fl, I, Mn, Mo, Se