Vitamins
*Extra notes
*Enzymes
*Deficiency + Symptoms
*Diagnosis
*Function + Distribution
Folic Acid=Folate=B9 (Hematopoietic)
-Most common vitamin deficiency among pregnant women and alcoholics
-Folic Acid Dihydrofolic Acid THFPurine syn/TMP syn/serine syn from glycine/methionine syn from
homocysteine by Dihydrofolic reductase
- can cause a nutritional anemia (macrocytic) because of the accumulation of large, immature RBCs precursors called
megaloblasts due to decreased syn of purines and increased demand of folic acid during pregnancy, poor absorption
caused by alcoholism or drug treatments that inhibit Dihydrofolic reductase.
-neural tube defects (NTDs) like spinal bifida and anencephaly.
Cobalamin=B12 (Hematopoietic)
Homocysteine (Hcy) methionine by B ( )12 methyl-cobalamin
Odd # FA/some AA succinyl CoA by B (methylmalonyl12 deoxyadenosyl-cobalamin)
-In animals B is obtained by the intestinal microbiota or by diet from liver, red meat, eggs, dairy, fortified cereals;
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approximately 2-5mg is stored unlike other water-soluble vitamins.
-deficiency is determined by the amount of methylmalonic acid in the blood.
-symptoms similar to megaloblastic anemia; pernicious anemia because of absorption and destruction of gastric parietal
cells that make IF that carries B through the ileum; CNS defects because of accumulation of FA in cells.
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Ascorbic Acid=V (non-B complex)
C
-a reducing agent: its role is to keep iron of hydroxylases in the reduced state
-maintenance of connective tissue and wound healing
-deficiency causes scurvy: sore, spongy gums, loose teeth, fragile blood vessels, hemorrhage, swollen joints, bone change,
and fatigue; microcytic nutritional anemia can occur.
-vitamin C is a group of nutrients that includes V and -carotene (V ), which are antioxidants that can decrease the
EA
incidence of some chronic diseases like cardiovascular disease and cancers.
Pyridoxine=VB6 (collective terms for pyridoxine, pyridoxal, + pyridoxamine…derivative of pyridine; “other” group)
-subgroups differ by functional group attached to ring.
- pyridoxine occurs in plants; pyridoxal + pyridoxamine are found in foods for animals
-all three are precursors of active enzyme that is a coenzyme for many enzymes involved in pyridoxal phosphate (PLP)
transamination, deamination, decarboxylation, and condensation.
-deficiency can be caused by , a drug to treat tuberculosis, that can induce deficiency by forming an inactive PLP.Isoniazid
Other than that, rare deficiencies occur in infants with low B6 formula, women taking oral contraceptives, and those with
alcoholism.
-toxic when taken at more than 500mg/day (only water-soluble vitamin with toxicity).
Thiamine=B1
-Active form=Thiamine pyrophosphate (TPP)
-TPP is a coenzyme in the formation of degradation of -ketols by and in the oxidative decarboxylation of transketolase
-keto acids; also, is a coenzyme for and which is important for pyruvate dehydrogenase -ketoglutarate dehydrogenase
tissues in the CNS
-deficiency induces production of ATP and therefore cellular function.
-deficiency is diagnosed by an increase of RBC transketolase activity with addition of TPP.
-Beriberi occurs due to severe thiamine deficiency where polished rice is a major component of diet. Characterized by
either dry (peripheral neuropathy-weakness, numbness, pain especially in legs) or wet (edema, accumulation of fluid,
because of dilated cardiomyopathy)
-Wernicke-Korsakoff Syndrome is associated with chronic alcoholism and is characterized by mental confusion, gait
ataxia, nystagmus (to and fro motion of eyeballs), and ophthalmoplegia (weakness of eye muscles) with Wernicke
encephalopathy, memory problems, hallucination, and Korsakoff dementia.
Niacin=Nicotinic Acid=VB3
-found in unrefined and rich grains, cereals, milk, and lean meats
-active forms are nicotinamide adenine dinucleotide nicotinamide adenine dinucleotide phosphateNAD+ and NADP+
-deficiency causes pellagra, a disease involving the skin, GI tract, and CNS. Symptoms follow the three D’s and
occasional fourth D: dermatitis (photosensitivity), diarrhea, dementia, and maybe death; hartnup disorder is characterized
by defective absorption of tryptophan can cause pellagra symptoms.
-corn diets can cause pellagra because they are low in niacin and tryptophan.
-Niacin is particularly useful in treatment of type IIb hyperlipoproteinemia in which both VLDL and LDL are elevated.
Niacin raised HDL.
Riboflavin=VB2
-active forms are flavin mononucleotide ( ) and flavin adenine dinucleotide (FMN and FMNH2 FAD and FADH2). They
are sometimes attached to flavoenzymes and cause the oxidation or reduction id a substrate.
-no associated with a major human disease but does accompany other diseases.
-deficiency symptoms include dermatitis, cheilosis (fissuring at the corners of mouth), and glossitis (tongue appearing
smooth and dark).
Biotin= VB7
- a coenzyme in carboxylation reactions and serves as a carrier of CO2.
-it is covalently bound to the -amino group of lysine residues in biotin dependent enzymes
-biotin deficiency doesn’t occur naturally because biotin is greatly distributed in food plus a large percentage is supplied
by the intestinal bacteria.
-Raw egg white (20 eggs/day) to diet can cause symptoms of biotin deficiency like dermatitis, hair loss, loss of appetite,
and nausea. Raw egg has a glycoprotein named avidin that binds to biotin not allowing it to absorb in the intestine.
Pantothenic Acid= VB5
-is a component of that transfers acyl groups; examples: succinyl CoA, fatty acyl CoA, acetyl CoACoA
-also, a component of fatty acid synthase
-eggs, liver, and yeast are the most important sources.
-no deficiency
Vitamin A=retinol=B-carotene
-from animal resources as retinol (preformed VA), a retinoid. Retinoids are a family of structurally related molecules that
are essential for vision, reproduction, growth, immune function, and maintenance of epithelial tissue.
-Structure:
1. Retinol: storage form of VA
2. Retinal (vision): aldehyde derived from the oxidation of retinol. Both retinol and retinal can be interconverted.
3. Retinoic acid (mediates most actions of retinoids): from oxidation of retinal. Cannot be reduced in body.
4. b-carotene: can produce two molecules of retinal. VA activity of b-carotene is only 1/12 of retinol.
-Function:
1. Visual Cycle: VA is a component of the rod and cones cells.
2. Epithelial cell maintenance: differentiation of epithelial tissues and mucus secretion and thus supports the body’s
barrier-based defense against pathogens.
3. reproduction: retinol and retinal are essential for normal reproduction, supporting spermatogenesis and preventing fetal
resorption in females.
*Retinoic acid is inactive in maintaining reproduction and in the visual cycle but promotes growth and differentiation in
epithelial cells.
Distribution:
-liver, kidney, cream, butter, and egg yolk are good sources of preformed VA. Yellow, orange, dark-green beggies are a
good source of carotenes.
Requirement:
-900 retinal activity equivalents (RAE) in males and 700 RAE in females.
Deficiencies:
Night blindness
Corneal ulcerations
Xerophthalmia= dryness of conjunctiva
and cornea
Acne/psoriasis
Toxicity:
Hypervitaminosis A <7.5mg/day
-dry skin, hepatomegaly, inc. intracranial
pressure, teratogenesis in fetus
Isotretinoin
-inc. TAG, cholesterol, risk for CVD
Vitamin K
-K is found in cabbage, spinach, kale, egg yolk, and liver. 120 ug/day for men and 90ug/day for females.
-deficiency is unusual because of good resources, but if intestinal bacteria population in decreased due to antibiotic, it can
cause hypoprothrombinemia (bleeding tendency). Deficiency can also affect bone health.
-newborns don’t have the bacteria to synthesized vitamin K so its recommended that all newborns receive a single dose.
-toxicity: can cause hemolytic anemia and jaundice
Vitamin D
-active form is 1,25 dihydroxycholecalciferol or calcitriol it either represses or stimulates gene transcription.
Vitamin E=tocopherols
-antioxidant in prevention of nonenzymatic oxidations and peroxidation of polyunsaturated FA by O2 and free radicals.
-veggie oils have rich sources while liver and eggs have moderate sources. 15mg/day. Requirement increases as the intake
of polyunsaturated FA increases to limit FA peroxidation
- newborn have low reserves, but breast milk has.
Deficiency is associated with defective lipids absorption and transport (like abetalipoproteinemia…defect in chylomicron
+ VLDL formation)
-not recommended to prevent chronic diseases.
-no toxicity; less toxic of fat-soluble vitamins
Deficiencies:
1. Nutritional rickets
2. Renal osteodystrophy
3. hypoparathyroidism.
Minerals
-minerals are inorganic (non-carbon made) substances required in small amounts by the body and they function in
formation of bones and teeth, fluid balance, nerve conduction, muscle contraction, signaling, and catalysis.
*write down daily doses
Macrominerals (>100mg/day) Microminerals/Trace (1-100mg/day) Ultratrace (<1mg/day)
Calcium (Ca) Chromium (Cr) Iodine (I)
Chloride (Cl) Copper (Cu) Molybdenum (Mo)
Magnesium (Mg) Fluorine as Fluoride (F) Selenium (Se)
Phosphorus (P) Iron (Fe)
Potassium (K) Manganese (Mn)
Sodium (Na) Zinc (Zn)
MACROMINERALS
Calcium & Phosphorus
-they are considered together because they are components of hydroxyapatite (Ca OH), which makes up bones and
5[PO4]3
teeth
Calcium
-most abundant mineral in the body with 98% found in bones. The remainder is involved in signaling, muscle contraction,
and blood clotting.
-no deficiency, but U.S. intake is insufficient for optimal bone health.
-toxicity at >2500mg/day.
-hypercalcemia can result from over production of parathyroid hormones (PTH) that can cause constipation and kidney
stones; hypocalcemia can result from deficiency of PTH or vitamin D.
Phosphorus
-most abundant intracellular anion most as phospholipids, nucleic acids, ATP, kinases, phosphorylases.
-Widely distributed in milk
-deficiency is rare
-hypophosphatemia can be caused by refeeding carbs to malnourished patients, overuse of aluminum contains antacids.
Muscle weakness is common. Hyperphosphatemia is caused by decreased PTH levels, excess P can combine with Ca to
form crystals that deposit in soft tissue.
*hormonal regulation: serum levels of P and Ca are controlled by calcitriol (in kidneys) the active form of vitamin D and
PTH, both of which respond to a decrease in serum Ca.
Calcitriol leads to
bone resorption Ca absorption in gut Ca reabsorption in kidney
serum Ca
PTH leads to
bone resorption P reabsorption in kidney Ca reabsorption in kidney
serum Ca
Magnesium
60% of magnesium is in bone, but accounts for 1% of bone mass.
-Deficiency: hypomagnesemia can result from decreased absorption or increased secretion of Mg. Symptoms include
hyperexcitability if muscles and nerves, and cardiac arrhythmias. With hypermagnesemia, hypotension is seen.
Sodium, Chloride, and Potassium
-all play an important role in water balance, osmotic equilibrium, acid-base balance (pH), and the electrical gradients
across cell membranes that are essential for the functioning of neurons and myocytes.
-no deficiency of NaCl
-Na plays a role in hypertension. Ingestion of Na stimulates thirst centers in the brain and secretion of antidiuretic
hormone from the pituitary, leading to water retention, increasing plasma volume and consequently BP.
-(Na) hyper/hypo artemia is caused by either excessive water loss or decreased ability to excrete water and can cause
severe damage.
-K is under ingested in U.S. because fruits and veggies are under ingested. However, K is a intracellular electrolyte; there
is a narrow range for normal serum K levels and even most changes can cause hyper-/hypokalemia which can result in
cardiac arrhythmias and skeletal muscle weakness.
MICROMINERALS/TRACE MINERALS
Copper
-key component for several enzymes such as (oxidizes iron), (Transfers electrons from ferroxidases cytochrome c oxidase
cytochrome c to oxygen in ETC), (hydroxylates dopamine to norepinephrine), dopamine B-hydroxylase tyrosinase
(synthesizes melanin), (forms cross links in collagen and elastin) and (converts lysyl oxidase superoxide dismutase
superoxide to H2O2)
Iron
-Iron is used to make a variety of components that are catalytic (catalyst-increases the rate of a chemical reaction) like
hydroxylases (e.g., prolyl hydroxylase) and non-catalytic
-can be linked to sulfur, in Fe-S proteins seen in the ETC or it can be a part of a heme prosthetic group in hemoglobin,
myoglobin, and cytochromes.
-free ionic iron is toxic because it can cause ROS
-meat, poultry, some shellfish, ready-to-eat cereals, lentils, and molasses.
-Uptake: Tf bound Fe binds to TfR (receptors) on erythroblasts and other Fe requiring cells and is taken up by
endocytosis. Fe is un-bound and use or stored in ferritin and the TfR is recycled.
-Deficiency: can result in microcytic, hypochrome (chrome=pigement) anemia, the most common anemia in the U.S. as a
result of decreased hemoglobin synthesis and decrease RBC size.
-Excess: can cause poisoning, genetic defects like hereditary hemochromatosis (HH) which means there is no way to get
rid of the iron. Hyperpigmentation and Hyperglycemia “bronze diabetes” is also seen.
Manganese
-important for the function of several enzymes
-whole grains, legumes, nuts, and tea are good sources.
-Mn deficiency in humans is rare.
-Toxicity is also rare
Zinc
-Absorption, storage, transport: 10% of iron is absorbed to
replace Fe lost.
-absorbed by heme carrier protein (heme) or DMT-1 (non-
heme)
-heme oxygenase (oxygen to molecule) removes Fe from
heme
-ferrireductase (reduces a molecule) reduces Fe to Fe
3+ 2+
-now Fe can have two fates: be oxidized (made more
2+
positive) to Fe and stored in ferritin or transported to the
3+
membrane of the liver in ferroportin and taken up in the
plasma by transferrin, Tf (1/3 saturated by Fe). Hepcidin
induces internalization and lysosomal degradation of
ferroportin.
-Recycling: macrophages phagocytize damaged RBCs
freeing heme Fe that is sent out by ferroportin, oxidized by
ceruloplasmin and transported by Tf. this meets our daily
need.
-plays important structural and catalytic functions in the body.
-hundreds of enzymes require Zn for activity like (ethanol acetaldehyde) alcohol dehydrogenase, carbonic anhydrase
(bicarbonate buffer system), (heme synthesis, inhibited by lead), .porphobilinogen synthase superoxide dismutase
-dietary sources of zinc include meat, fish, eggs, and dairy products.
-phylates can bind to Zn in the intestine, decreased absorption, that can cause a deficiency.
Other Microminerals
-Chromium potentiates the action of insulin. It is found in fruits, veggies, dairy products, and meat.
-Fluorine is added to water to reduce dental caries (cavities).
ULTRATRACE MINERALS
Iodine (I)
-Utilized in the synthesis of thyroid hormones T and T that are required for development, growth, and metabolism.
3 4
-Circulating iodine is trapped in the thyroid, oxidized by thyroperoxidase (TPO), and bound to tyrosine residues,
thyroglobulin (Tg), to form mono- and di-iodothyronines (MIT and DIT, respectively) and their subsequent spontaneous
crosslinking to form T and T .
3 4
-under normal conditions 90% of secreted thyroid hormone is T4 that is carried by transthyretin. In the liver and brain T4
is converted to T3 by Se-containing T3 binds to a nuclear receptor that binds DNA at thyroid responsedeiodinases. .
-dairy products, seafood, and meat are primary sources of I.
-hypothyroidism: not enough thyroid hormones; under-ingestion of iodine can result in goiter (enlargement of thyroid in
response to excessive stimulation of thyroid stimulating hormone (TSH)). This can cause fatigue, weight gain, decreased
thermogenesis, and decreased metabolic rate. In infant development, hypothyroidism can cause intellectual disability,
hearing loss, spasticity, and short stature.
-Hyperthyroidism: overproduction of thyroid hormones by over-ingestion of I-containing supplements. Most common
cause is Grave’s disease in which an antibody that mimics the effects of TSH is produce which causes more production of
thyroid hormones. This can cause nervousness, weight loss, increased perspiration and heart rate, goiter, and protruding
eyes (exophthalmos).
Selenium (Se)
-is present in 25 proteins called selenoproteins derived from serine. Selenoproteins include glutathione peroxidase that
oxidizes glutathione in the reduction of H2O2 to H O,
2thioredoxin reductase that reduces thioredoxin, a coenzyme of
ribonucleotide reductase and deiodinases that remove iodine from thyroid hormones.
-meat, dairy, and grains are important dietary sources
-Deficiency causes Keshan Disease, a cardiomyopathy causes by eating food from Se-deficient soil.
-toxicity or selenosis causes brittle nails and hair.
Molybdenum (Mo)
-is a cofactor for a small number of mammalian oxidases like aldehyde oxidase, sulfite oxidase, xanthine oxidase.
-no toxicity
-no deficiency
-legumes are important dietary sources
Cobalt (Co)
-a component of VB12
-no recommended dietary allowance or daily reference intake has been established
