-
-
-
-
vitamin B5
pantothenic acid
-
-
-
-
-
Government mandates fortification with which B vitamins?
1,2,3,9
-
active form of thiamin
- TPP - thiamin pyrophosphate
- (B1)
- cooking destroys it
-
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
-
PDH coenzymes
- B1 - thiamin - TPP
- B2 - riboflavin - FAD
- B3 - niacin - NAD+
- B5 - pantothenic acid - CoA
-
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
-
sources of thiamin
- pork
- legumes
- nuts & seeds
- (unstable during cooking)
-
regulation for thiamin toxicity
- absorption declines rapidly with increased consumption &
- kidneys excrete it rapidly
-
alchohol related deficiencies
- thiamin (B1)
- riboflavin (B2)
- pryodoxine (B6) - rare
- potassium
- magnesium
-
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)
-
glutahione reductase depends on...
- FAD (riboflavin) as a prosthetic group
- NADPH (niacin) so it can reduce peroxides
-
sources of B2
- (riboflavin)
- milk, yogurt
- bread products
- 95% is bioavailable
-
refined grain products are enriched with...
- thiamin
- riboflavin
- niacin
- folic acid
- iron
-
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
-
riboflavin toxicity
no cases
-
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
-
lactates conversion to pyruvate requires...
NAD+ (niacin/B3)
-
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)
-
sources of niacin
- meat (liver), poultry, fish
- enriched milk, grains, cereals
- can be converted from tryptophan using riboflavin, B6 & Fe
-
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
-
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.
-
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)
-
sources of panthotenic acid
- widespread in all foods
- freezing/canning/processing/refining decreases content
-
-
-
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.
-
coenzyme functions of B6
- transamination
- deamination
- carboxylation
- condensation
-
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 aasregualtion of blood homocysteine - PLP-dependent enzymes convert homocysteine to cysteine
- helps convert tryptophan to B3
-
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
-
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
-
sources of B6
- fortified cereals, meat, fish, poultry
- 75% bioavailable
- heat destroys up to 50%
-
B6 deficiency
- rare, but alchoholism increases risk
- TBC (tuberculosis) drug inactivates endogenous PLP
- microcytic hypochromic anemia
- seborrheic dermatitis
- neurological symptoms -confusion, depression, convulsions
-
causes of seborrheic dermatitis
deficiency of PLP (B6) or riboflavin (B2)
-
B6 toxicity
nerve damage affecting walk
-
biotin
- B7
- aka biosil, vitamin H, coenzyme R - necessary for bacterial growth
- prosthetic group for carboxylases
- carrier of activated carbon dioxide
-
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
-
souces of biotin
- intestinal bacteria
- cauliflower, liver, peanuts, cheese, egg yolk - cook eggs to prevent avidin in egg white from binding biotin
-
biotin deficiency
- anticonvulsive drugs
- hairloss & rash...convulsion & neurological disorders
- changes in blood pH...coma, death
-
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
-
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
-
folate deficiency
- NTDs
- megaloblastic anemia due to insufficient synthsis of purines and TMP (thymine monophosphate) needed for DNA, so cells can't divide
-
cause of megaloblastic anemia
- folate or B12 deficiency
- RBC precursors in bone marrow can't form new DNA & divide
-
folate can mask deficiency of...
- B12
- high folate can exacerbate neurological problems associated woth B12 deficiency for this reason
-
folate toxicity
hives & respiratory distress if person has a sensitivity
-
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)
-
sources of B12
- microorganisms - can be obtained from animals
- fortified cereals
- ~50% bioavailable in foods
-
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
-
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
-
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
-
riboflavin and vitamin B6 deficiency can cause
seborrheic dermatitis
-
abnormal maturation of red blood cells
- B6 deficiency (microcytic hypochromic anemia)
- folate deficiency (megaloblastic)
- B12 deficiency (megaloblastic)
-
malabsorption of biotin (B7)
from raw eggs
-
impaired DNA synthesis
folate (B9) deficiency
-
synthesis of glucose from pyruvate in the pathway of gluconeogenesis requires
B7 / biotin
-
synthesis of nonessential amino acids in the transamination reactions requires
B6 / PLP
-
Microcytic hypochromic anemia associated with B6
deficiency is caused by ____________ due to ________________.
low hemoglobin production / impaired heme synthesis from amino acid precursors
-
Ex. of vitamin-like compounds that are essential for cell function:
- choline
- carnitine
- inositol
- taurine
- lipoic acid
-
Binding of ___________ to ____________ is an
essential step in muscle contraction
Ca2+/troponin
-
Which of the following is required for synthesis
of ATP in a substrate-level phosphorylation reaction?
Mg
-
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)
-
Zinc is stored in the cells bound to ___________
in the molecule of _____________.
cysteines/metallothionein
-
Zinc deficiency can result in
- night blindness
- skin lesions and rashes
- increased susceptibility to infections
-
thioredoxin reductase
reduction of dehydroascorbate
-
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
-
Copper as _____________ plays an important role in ______________.
a transition metal/ the electron transport in mitochondria
-
Glutathione assists ________________ in reducing
hydrogen peroxide.
glutathione peroxidase
-
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
-
a cofactor that helps glutathione peroxidase to reduce H2O2
Se
-
a coenzyme that helps glutathione reductase to reduce GSSG
FAD+ / riboflavin / B2
-
Thioredoxin reductase is a uses ________to reduce thioredoxin and other substrates.
- NADPH
- selenocysteine is a component of TRR
-
Required for the oxidative decarboxylation of pyruvate
-
vitamin C functions
- absorption of Fe in small intestine
- coenzyme - formation & maintenance of connective tissue/collagen
- antioxidant defense
-
2 biologically active forms of vitamin C
- ascorbic acid
- dehyroascorbic acid
-
Most animals, but not humans, can synthesis what vitamin/mineral from glucose?
vitamin C
-
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
-
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
-
hydroxylation of collagen fibers requires ________ & helps ____
- vitamin C
- add stability to triple helixes
-
food sources of vitamin C
- potatoes, citruis, tomoato, broccoli, strawberries, kiwi, cabbagee, spinach, green peppers
- vulnerable to heat & oxygen
- absoprtion decreases with increased intake
-
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
-
vitamin C toxicity
- N/A
- may cause abdominal cramps, diarrhea, nausea, nosebleeds
- excessive absorption of Fe & Fe induced oxidative damage
-
choline
- vitamin-like compound
- supports structural integrity of cell membranes
- needed for production of acetylcholine (neurotransmitter)
- source of methyl groups for DNA methylation
-
choline deficiency
fatty liver
-
carnitine
- vitamin-like compound
- synthesized from lysine in liver
- carries FAs from cytosol into mitochondria for TCA cycle
-
carnitine deficiency
abnormal FA metabolism
-
inositol
- vitamin-like compound
- synthesized from glucose
- phospholipid in cell membrane
- precursor to eicosanoids, hormone-like substances
- regulates intracellular Ca++
-
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
-
lipoic acid
- vitamin-like compound
- cofactor in energy-producing rxns in mitochondria (e.g. conversion of pyruvate to acetyl CoA)
- antioxidant
-
most essential nutrient
water
-
fluid compartments in body
- Body Water
- 2/3 - intracellular (cytoplasm & in organelles)
- 1/3 - extracellular (plasma, interstitial fluid, lymph, CSF, etc.)
-
Water's functions:
- heat capacity - prevents overheating / freezing
- cooling - perspiration
- chemical reactions - solvent
- pH balance
- body fluids - transport, shock absorption, lubrication, cleansing
-
electrolytes
- Na+ - extracellular cation
- K+ - intracellular cation
- Cl- - extracellular anion
- PO4 3- -intracellular anion
- membrane pumps balance them
-
Na/K pump
3 Na+s out for every 2K+s in
-
daily fluid intake & output
- input: food, beverages, metabolism
- output: kidneys/urine, insensible (skin, lungs, coughing, runny nose), feces
-
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+
-
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
-
dehydration
- from diarrhea, vomitting
- major killer
- signs: fatigue, dry mouth, headache, dark urine, diminished physical & mental performance
- IV or oral rehydration
-
water intoxication
hyponatremia
-
major minerals
- DRI > 100 mg/day
- Ca
- P
- S
- K
- Na
- Cl
-
minor / trace minerals
- DRI <100 mg/d
- Mg
- Fe
- Zn
- Cu
- I
- Mn
- Se
-
factors decreasing mineral bioavailability
- phytate
- polyphenols
- oxalate
- competition
- high pH
- decreased need
- fiber
-
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)
-
sources of sodium
processed foods (soy sauce, picked foods, salty meats, cheeses, soups)
-
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..
-
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
-
salt sensitivity
- common in obese / insulin-resistant individuals
- African-Americans more sensitive
- women more sensitive
- aerobic exercise can decrease sodium sensitivity
-
potassium functions
- major intracellular cation
- major mineral
- works with Na+ to maintain membrane potential - nerve impulse transmission, muscle contraction, heart function
-
sources of potassium
fruits, veggies, grains (unprocessed)
-
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
-
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)
-
Potassium for lowering disease risk
- decreased risk of stroke
- increased bone mineral density
- decreased (Ca++) kidney stone formation
-
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
-
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
-
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
-
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)
-
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
-
Hormonal Regulation of Blood Calcium
- calcitriol: active vitamin D
- PTH: increases Ca absorption & reabsorption through transcriptional of transporters & bone resorption
- calcitonin: bone formation (thryroid)
-
hypocalcemia
- low blood calcium
- cause = kidney failure, PT disorders, vitamin D deficiency
- signs = muscle spasms, facial grimacing, convulsions
- osteoporosis
-
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
-
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)
-
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
-
sources of chloride
- table salt
- processed foods
-
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
-
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
-
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
-
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
-
sources of phosphorus
- meat, milk, eggs
- processed foods have phosphate salts
- seeds/beans, but can't be absorbed well due to phytate
-
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
-
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
-
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
-
Mg deficiency
- rare
- bone stores keep cell & body fluid levels constant
-
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
-
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
-
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
-
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 -
-
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
-
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
-
HTN reduction
- lower Na
- decrease obesity
- increase Ca
- increase Mg
- increase K
-
Osteoporosis & minerals
associated with low Ca, P, Mg
-
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
-
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
-
monocytes use what to kill bacteria?
- hypochlorous acid (bleach) produced by myeloperoxide (a heme protein)
- requires Fe for heme protein, Cl- & H2O2
-
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
-
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
-
Iron Turnover & loss
- RBC formation & destruction
- lost in feces & sloughed mucousal & skin cells
- menstruation
- GI issues: IBD, bowel cancer, hookworm infection
-
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
-
sources of Fe
- seafood, red meat, poultry
- fortified cereals
- tofu, legumes
- consume veggies w/ vitamin C rich foods to maximize bioavailability
-
Fe deficiency
- most common nutritional deficiency
- most prevalent in 6-24 mo. old children
- anemia - fatigue, rapid HR, palpitations, rapid breathing
-
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
-
microcytic hypochromic anemia
- pyrodoxil (B6) deficiency - needed for heme synthesis or
- Fe deficiency
-
Fe toxicity
- OD from supplements - nausea, vomiting, diarrhea, rapid heartbeat, confusion, death
- chronic excessive intake - may increase risk of CVD, cancer, T2DM, neurodegenerative disease
-
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
-
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
-
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
-
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
-
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)
-
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
-
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
-
sources of Zn
- protein rich foods: dark meat, seafood, oysters, clams, wheat bran (but poorly absorbed ue to phytate & fiber)
- dairy, grains
-
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
-
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
-
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)
-
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
-
selenocysteine
- 21st aa
- can also be synthesized from serine during translation & inserted at UGA codon
-
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
-
hypothyroidism
severity increased by iodine & selenium deficiencies
-
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
-
sources of Se
organ meats, seafood (but not good source of Se-aas), grains
-
Se deficiency
- Keshan disease - (viral) cardiomyopathy in China - little Se in soil
- chronic total parenteral nutrition
-
Se toxicity
- inorganic Se is toxic
- brittle hair & nails / hair loss
-
iodine
- ultratrace / micromineral
- non-metallic
- iodide - anion
- erosion depletes I
-
functions of I
- component of thyroid hormones: triiodothyronine (T3) & thyroxine (T4 - 95%)
- T3 is the biologically active form
- regulates body temperature, BMR, reproduction, growth
-
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
-
sources of I
- seafood
- added to salt & cattle feed
-
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
-
I toxicity
- inhibited synthesis of thyroid hormones
- inhibition by substrate (I)
- goiter
-
copper
- trace / micromineral
- transition metal Cu+1, Cu+2
- Cu+2 is main form in body
- redox rxns, scavenges free radicals
-
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
-
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
-
sources of Cu
organ meats, shellfish, nuts, seeds, legumes, chocolate
-
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
-
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
-
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
-
Mn absorption & metabolism
- poor absorption to protect against toxicity
- transferrin binds it & transports it
- excretion regulates levels
- bile is main excretory route
- no storage
-
Mn sources
cereals, nuts, tea, some fruits
-
Mn deficiency
- nontrauma epilepsy, PKU, ALS, MS may increase marginal risk of deficiency
- may impair CHO & fat metabolism & growth
-
Mn toxicity
occupational exposures only
-
fluoride
- ultratrace / micromineral anion
- bones & teeth contain most
- stimulates mineralization - reacts with hydroxyapatite to form fluoroapatite
-
Fl absorption & excretion
- ~100% absorption in water
- 50-80% absorption in food
- excess excreted in urine
-
Fl deficiency
dental caries, bone integrity hampered
-
Fl toxicity
- fluorsis
- acute toxicity - from hemodialysis pts - nausea, abnormal heart rhythm, fractures
-
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
-
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
-
-
-
sources of Cr
brewer's yeast, beer, processed meats, whole grains, green beans, broccoli, spices, stainless steel dishes
-
Cr deficiency
- difficult to assess
- decreased insulin-mediated glucose uptade - elevated blood glucose & insulin
- blood lipid abnormalities
-
Cr toxicity
no dietary cases
-
molybdenum
- Mo
- ultratrace element
- in 3 enzymes found in liver for sulfite -->sulfates, breakdown of nucleotides produce H2O2, hyroxylation of endogenous compounds, drugs, toxins
-
Mo absorption
- 80-90%
- rapid excretion in urine & bile
- dietary Cu can inhibit Mo absorption
-
Mo sources
peas, beans, cereals, organ meats
-
Mo deficiency
TPN or genetic disorder - weakness, confusion, night blindness
-
Mo toxicity
high intake inhibits Cu absorption - treatment for Wilson's disease
-
Ultratrace minerals
- ultratrace minerals <1 mg/d
- Cr, Fl, I, Mn, Mo, Se
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