Lecture 35 Flashcards
Vitamins
vitamin
essential for normal growth and nutrition and are required in small quanities in the diet because they cannot be synthesized by the body
pg 877
minimizing vitamin losses
- prevent enzymatic destruction: refrigerate most fruits, vegetables, and juices to slow breakdown of vitamins
- protect from light and air: store milk and enriched grain products in opaque containers to limit riboflavin losses, store cut fruits and vegetables in the refrigerator in airtight wrappers, reseal juice containers before refrigerating
- prevent heat destruction or losses in water: wash intact fruits and veggies before cutting or peeling to prevent vitamin losses during washing; cook fruits and veggies in a microwave oven, or quickly stir-fry, or steam them over a small amount of water to prevent vitamin loss in cooking water; recapture dissolved vitamins by using cooking water for soups, stews, or gravies; avoid high temperatures and long cooking times
pg 877
fat soluble vitamins
- A, D, E, K
- toxicity possible because stored in fat and liver
- malabsorption with steatorrhea (cystic fibrosis)
- reduced fat intake may cause deficiency -> need to consume with fat, drugs that block fat absorption
pg 879
vitamin A -> retinoids
retinol:
- preformed vitamin A, storage form
- retinol released from liver transported through blood to extrahepatic tissue by retinol-binding protein (RBP) complexed with transthyretin (TTR)
retinal:
- derived from oxidation of retinol
- readily inconvertible (retinol to retinal)
retinoic acid:
- oxidized from retinal (cannot be reduced back)
- excreted form
β-carotene:
- provitamin - oxidatively cleaved in intestine to release two molecules of retinal - inefficient
- genetic variations in β-carotene 15,15’-oxygenase
vitamin A is a potent mutagen in gene expression
pg 881
retinoic acid
growth and differentiation
- retinoic acid binds to retinoic acid receptor (RAR) in nucleus of target tissues (epithelial tissue)
- binds to response element -> recruits activators or repressors and regulates expression of retinoic-dependent protein (e.g. keratin) -> epithelial tissue integrity by regulating differentiation and mucus secretion
- normal growth in children
- bone remodeling
pg 882
retinol and retinal
reproduction (normal levels)
- supports spermatogenesis
- normal fetal development (prevents fetal resorption)
pg 882
sources of vitamin A
- milk, cheese, cream, butter, fortified margarine, eggs, liver
- β-carotene: spinach, other dark green leafy veggies, apricots, cantaloupe, squash, carrots, sweet potatoes, pumpkin
retinal: visual cycle
- 11-cis retinal bound to protein opsin in rhodopsin (a visual protein, a G-protein coupled receptor)
- exposure to light -> rhodopsin bleaching -> photochemical isomerization -> decreased cGMP -> activates G protein transducin -> trigger nerve impulse -> transmitted to optic nerve
- regeneration of all trans retinal
- cell membrane rich in n-3 PUFA can increase the efficiency of rhodopsin
vitamin A in the eye maintains a healthy cornea
pg 883
hypovitaminosis A
- takes a year or more to develop a deficiency
- impaired immunity correlates with vitamin A deficiency in children -> the goals of WHO include vitamin A supplementation, vitamin A declines during infection
- changes in epithelial cells results in keratinization -> rough, dry, and scaly skin
Eyes
- night blindness (nyctalopia): first detectable sign
- can be a loss of visual cells
- blindness (severe deficiency)
- xerophthalmia
- xerosis is the first stage where the conjunctiva and cornea become dry and hard -> coneal ulcers -> opaque scare tissue -> blindness
pg 884-885
pharmaceutical forms of vitamin A
skin conditions:
- retinoic acid derivative -> tretinoin used for treating mild acne and skin aging -> topical use (e.g. retin-A)
- isotretinoin is teratogenic -> contraindicated in women with childbearing potential (e.g. absorica) -> lethal for fetuses (iPLEDGE program required)
pg 886
hypervitaminosis A
- can occur with concentrated amounts of the preformed vitamin A from animal foods, fortified foods, or supplements
- consuming extremely excessive amounts of β-carotene from supplements can be harmful
- acute toxicity symptoms include blurred vision, nausea, vomiting, vertigo, headaches, and pressure in the skull
- chronic toxicity -> liver damage -> bone defects (increased osteoclast activity)
pg 887
vitamin D -> calcitriol
- cholecalciferol transported to liver bound to vitamin D-binding protein
- plant version is vitamin D2 or ergocalciferol
- 25-hydroxycholecalciferol -> predominant form of vitamin D in serum
- formation of active form of vitamin D -> 1,25 dihydroxycholecalciferol (calcitriol) is strictly regulated by serum phosphate (PO43-) and calcium (Ca2+) ion concentrations
- calcitriol and PTH work together to regulate serum levels of calcium and phosphorus
- nutrient of public health concern
pg 889
serum 25-hydroxyvitamin D concentrations and health
> 20 ng/mL typically considered adequate for bone and overall health in healthy individuals
pg 890
sources of vitamin D
exposure to sunlight necessary to maintain adequate vitamin D
- sufficient synthesis with five to ten minutes of sun exposure few times a week
- higher melanin needs more time
- sunscreens with SPF > 8 inhibit vitamin D synthesis
- low levels of vitamin D common at end of winter months and in northern latitudes (above 40th parallel)
food sources
- few animal foods provide significant source: eggs, liver, butter, some fatty fish, maybe mushrooms
- fortified foods: milk, margarine, cereals, infant formulas
pg 891
clinical indications - vitamin D
Nutritional Rickets
- bone demineralization (loss of calcium) -> rickets in children and osteomalacia in adults
- rickets: continued formation of collage matrix in bone with incomplete mineralization -> soft bones
- osteomalacia: demineralization of pre-existing bones -> increased susceptibility to fracture
Hypoparathyroidism
- lack of PTH -> hyperphosphatemia and hypocalcemia
Toxicity
- enhanced calcium absorption -> hypercalcemia -> deposition of calcium salts in soft tissues
- kidney stones
- vascular calcification
pg 892
vitamin E -> tocopherol
- α-tocopherol is most biologically relevant
- works as an antioxidant (prevent non-enzymatic oxidation) -> prevents peroxidation of PUFA, LDL oxidation, cell membrane
- vitamin requirement increases with increase intake of PUFA
- breast milk provides vitamin E to newborn
- in adults, deficiency because of defective lipid absorption or transport
- found in lipid bilayers
- sources: leafy green veggies, plant oils, whole grains, liver, egg yolks, nuts and seeds
pg 894
vitamin E deficiency
- primary deficiency due to inadequate intake is rare
Symptoms:
- loss of muscle coordination and reflexes
- impaired vision and speech
- nerve damage
- erythrocyte hemolysis: premature infants, hemolytic anemia can be treated with vitamin E
pg 895
vitamin K -> k for koagulation
- several active forms: phylloquinone in plants (K1), menanquinone in intestinal bacteria (K2), menadiaone (synthetic vitamin K -> K2)
- hepatic synthesis of functional blood clotting proteins -> vitamin K-dependent carboxylation of several γ-glutamic acid residues to γ-carboxyglutamate (Gla) by the enzyme g-glutamyl carboxylase
- warfarin (rat poison -> anti-coagulant in low doses) inhibits regeneration of hydroquinone form of vitamin K from epoxide form by the enzyme vitamin K epoxide reductase (VKOR)
- bacterial synthesis in the digestive tract, liver, leafy green veggies (K1), milk, fermented foods (K2)
pg 897
carboxyglutamate (Gla) importance
- prothombin interaction with membrane
- Gla is a strong chelator of positively charged Ca2+
- prothombin-calcium complex binds to negatively charged membrane phospholipids on the surface of the damaged endothelium and platelets -> increases the rate of proteolytic conversion of prothombin to thrombin
- rare deficiency (antibiotic intake) -> hypoprothrombinemia in marginally malnourished individual
- ingle intramuscular dose of vitamin K as prophylaxis against hemorrhagic disease of the newborn
pg 898
water soluble vitamins
all the B vitamins and vitamin C
- washed out from body except B12 and folate
- B12 stored in liver for 3-4 years
- folate stored in liver for 3-4 months
- can be co-enzymes (ascorbic acid) or precursor to co-enzymes (FAD, NAD+)
- all others need to be replenished daily
aside
* vitamin B4 (adenine), B8 (inositol), B10 (PABA), and B11 (salicylic acid) aren’t considered vitamins anymore and aren’t essential in diet
pg 901