1
Q
vitamin
A
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
2
Q
minimizing vitamin losses
A
- 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
3
Q
fat soluble vitamins
A
- 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
4
Q
vitamin A -> retinoids
A
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
5
Q
retinoic acid
A
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
6
Q
retinol and retinal
A
reproduction (normal levels)
- supports spermatogenesis
- normal fetal development (prevents fetal resorption)
pg 882
7
Q
sources of vitamin A
A
- milk, cheese, cream, butter, fortified margarine, eggs, liver
- β-carotene: spinach, other dark green leafy veggies, apricots, cantaloupe, squash, carrots, sweet potatoes, pumpkin
8
Q
retinal: visual cycle
A
- 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
9
Q
hypovitaminosis A
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
10
Q
pharmaceutical forms of vitamin A
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
11
Q
hypervitaminosis A
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
12
Q
vitamin D -> calcitriol
A
- 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
13
Q
serum 25-hydroxyvitamin D concentrations and health
A
> 20 ng/mL typically considered adequate for bone and overall health in healthy individuals
pg 890
14
Q
sources of vitamin D
A
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
15
Q
clinical indications - vitamin D
A
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
16
Q
vitamin E -> tocopherol
A
- 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
17
Q
vitamin E deficiency
A
- 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
18
Q
vitamin K -> k for koagulation
A
- 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
19
Q
carboxyglutamate (Gla) importance
A
- 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
20
Q
water soluble vitamins
A
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
21
Q
vitamin B1 -> thiamine (TPP)
A
- thiamine pyrophosphate (TPP) is the active form
- a cofactor for several dehydrogenase enzyme reactions: branched chain ketoacid dehydrogenase, α-ketoglutarate dehydrogenase, pyruvate dehydrogenase (links glycolysis to TCA), transketolase (HMP shunt; pentose phosphate pathway -> ribose-5-phosphate and NADPH)
- involved in energy providing pathways, especially important in highly aerobic tissues such as brain and heart
pg 903
22
Q
thiamine deficiency clinical conditions (low ATP)
A
Beriberi (Ber1Ber1 -> B1):
- dry: peripheral neuropathy especially in legs, affects nervous system, muscle wasting
- wet: edema due to dilated cardiomyopathy -> affects cardiovascular system
Wernicke-Korsakoff syndrome:
- severe deficiency due to dietary insufficiency or impaired intestinal absorption
- mental confusion, ophthalmoplegia, gait ataxia
- associated with alcohol abuse
pg 903
23
Q
thiamine food sources and losses
A
- food: whole grain, fortified, or enriched grain products, moderate amounts in all foods, pork
- avoid losses by: thiamin is easily destroyed by heat, leaches into water with boiling or blanching, steaming and microwaving are cooking methods that conserve thiamin
pg 904
24
Q
riboflavin food sources and losses
A
- easily destroyed by UV light and irradiation
- phototherapy of neonatal hyperbilirubinemia may need supplementation
- not destroyed by cooking
- riboflavin food sources: milk products (yogurt and cheese), enriched and whole grains, liver
pg 906
25
vitamin B2 -> riboflavin (FMN/FAD)
involved in energy metabolism
* FAD and FMN are derived from ribo**F**lavin
* flavin mononucleotide (FMN) and flavin adenosine dinucleotide (FAD) -> biologically active forms of vitamin B2
* FAD and FMN each can accept two hydrogen to form FADH2 and FMNH2
* tightly bound to flavoenzymes: NADH dehydrogenase (FMN) and succinate dehydrogenase (FAD)
## Footnote
pg 907
26
riboflavin deficiency
ariboflavinosis
* cheilosis (inflammation of lips) and corneal vascularization (memorize as B2C)
* inflamed eyelids, sensitivity to light
* sore throat, cracks and redness at the corners of the mouth
* painful, smooth and purplish red tongue
* skin lesions covered with greasy scales
## Footnote
pg 907
27
vitamin B3 -> niacin (nicotinic acid, nicotinamide, niacinamide, NAD+/NADP+)
* biologically active coenzyme forms are *nicotinamide adenine dinucleotide* (NAD+) and its phosphate derivative (NADP+) -> energy production
* serves as coenzymes in oxidation-reduction reactions -> coenzymes undergo reduction by accepting hydride ion -> NADH and NADPH, respectively
* NAD+/NADH ratio = redox state of the cell
* 60 mg tryptophan = 1 mg niacin (also precursor for melatonin and serotonin)
## Footnote
pg 909
28
niacin deficiency -> pellagra
* diarrhea, abdominal pain, and vomiting
* inflamed, swollen, smooth and bright red tongue
* depression, apathy, fatigue, loss of memory, and headache
* rash when exposed to sunlight (dermatitis ONLY in exposed areas)
* way to remember: the 3Ds -> diarrhea, dementia, and dermatitis
## Footnote
pg 910
29
Hartnup disease
* deficiency of neutral amino acid (tryptophan) transporters in proximal tubule and intestine
* neutral amino aciduria
* decrease absoprtion from gut
* decrease in tryptophan (precursor for niacin)
* pellagra-like symptoms
## Footnote
pg 910
30
niacin excess
* niacin flush dilates the capillaries and may be painful
* painful flush, hives and rash
* excessive sweating
* blurred vision
* liver damage
* impaired glucose tolerance
## Footnote
pg 911
31
hyperlipidemia treatment
* niacin at 100 times higher dose than RDA inhibits lipolysis in adipocytes
* reduces circulating free fatty acids
* reduces hepatic production of TAG and VLDL
* reduces LDL cholesterol
* treatment of type IIb hyperlipoproteinemia (a condition where both VLDL and LDL are elevated)
## Footnote
pg 912
32
niacin food sources and losses
* food: milk, eggs, meat, poultry, fish, whole-grain and enriched breads and cereals, nuts and all protein-containing foods
* vitamin can be lost from foods when it leaches into water, but resistant to heat
33
vitamin B5 -> pantothenic acid
* a component of CoA - function in the transfer of acyl groups
* CoA contains a thiol group (-SH) that carries acyl compounds (succinyl CoA, fatty acyl CoA, acetyl CoA, and acyl carrier protein domain of *fatty acid synthetase*)
* deficiency very rare -> widespread in foods, fatigue, nausea, vomiting, numbness, cramps, difficulty walking, WWII prisoners of war -> burning feet syndrome
## Footnote
pg 914
34
vitamin B6 -> pyridoxal phosphate (PLP)
* biologically active coenzyme is pyridoxal phosphate (PLP)
* PLP functions as coenzyme for a large number of enzymes (involving amino acids) -> transamination, decarboxylation reactions, etc
* required for glycogen phosphorylase
* alcohol destroys the vitamin (antagonist) -> displaces B6 from its active site
* deficiency is rare
* symptoms of deficiency: convulsions, hyperirritability, peripheral neuropathy and **sideroblastic anemia** (impaired hemoglobin synthesis and excess iron); depression, confusion, abnormal brain wave pattern
* *only water-soluble vitamin to have toxicity (sensory neuropathy), no complete recovery after vitamin discontinued*
* toxicity symptoms: depression, fatigue, irritability, headaches, nerve damage causing numbness and muscle weakness leading to inability to walk, convulsions, skin lesions
## Footnote
pg 916-917
35
sideroblastic anemia
* congenital X-linked or drug-induced
* vitamin B6 part of a rate-limiting reaction with glycine that forms hemoglobin
* presence of iron granules (blue) in a perinuclear ring formation in erythroblasts
## Footnote
pg 918
36
vitamin B7 -> biotin
* a coenzyme in carboxylation reactions -> carry activated CO2 (one carbon transfer) -> pyruvate carboxylase and acetyl CoA carboxylase
* readily available in diet and synthesized by _intestinal bacteria_ -> raw egg white contains a glycoprotein, avidin, that binds strongly with biotin and prevents its absorption from gut -> induce biotin deficiency if consume too many raw eggs
* **avidin in egg white avidly binds biotin**
## Footnote
pg 920
37
biotin deficiency symptoms
* depression, lethargy, hallucinations
* numb or tingling sensation in the arms and legs
* red, scaly rash around the eyes, nose and mouth
* hair loss
## Footnote
pg 921
38
vitamin B9 -> folate
* tetrahydrofolate (THF) is the reduced form of the vitamin and is the active coenzyme form
* involved in *one carbon metabolism*: THF receives a one carbon fragment from a donor and transfers it to intermediates in the synthesis of amino acids, purine nucleotide, and thymidine monophosphate (TMP or dTMP)
* naturally occurring folate is well tolerated and is well observed; optimal pH = 5.5-6; excess folic acid may mask hematological symptoms of vitamin B12 deficiency (use 5-MTHF form)
* food sources: dark green leafy veggies, legumes, fortified pasta, rice, breads, and cereals
* easily destroyed by heat and oxygen
## Footnote
pg 923-924
39
serine hydroxymethyltransferase
carbon (methyl group off serine) added to purine bases, thymine, S-adenosylmethionine (choline phospholipids, creatine, epinephrine, DNA methylation)
tetrahydrofolate -> N,N-methylene-tetrahydrofolate
## Footnote
pg 925
40
clinical indication of folate deficiency
* _increased demand_ (pregnancy and lactation) can cause inadequate serum levels
* _poor absorption_ because of pathology of intestine
* deficiency linked with an increased risk of neural tube defects, cardiovascular disease, cancer, and cognitive dysfunction
## Footnote
pg 926-927
41
**macrocytic/megaloblastic anemia**
* folic acid or B12 deficiency -> reduced synthesis of purine nucleotides and thymidine monophosphate (TMP) -> inability to make DNA and divide -> accumulation of *immature RBC precursors* (megaloblasts) in bone marrow and the blood
* smooth, red tongue (sore, atrophy of the papillae), mental confusion, weakness, fatigue, irritability and headaches
## Footnote
pg 926
42
**neural tube defect**
* a birth defect of the brain or spinal cord development
* *spina bifida* (spinal column doesn't close completely) and *anencephaly* (absence of a major portion of the brain, skull, and scalp) -> the most common NTD
* folic acid supplementation before conception and the first trimester reduces the risk
* critical folate-dependent development occurs in the first weeks of the fetal growth
* nerve damage and loss of function that are present at birth are usually more permanent -> no cure
## Footnote
pg 927
43
inhibitors of folate metabolism
chemotherapy, methotrexate (autoimmune diseases supplemented with folinic acid), antibacterial (sulfonamides) and antimalarial (pyrimethamine) drugs
## Footnote
pg 929
44
folate trap (methyl trap)
vitamin B12 deficiency causes functional folate deficiency
* secondary to the deficiency of vitamin B12
* *methionine synthase* is B12 dependent
* accumulation of 5-methyl-THF
other deficiencies: aspirin, oral contraceptives, smoking
## Footnote
pg 930
45
vitamin B12 -> cobalamin
* required for: *remethylation* of homocysteine to methionine (folate trap) and *isomerization* of methylmalonyl CoA coming from AA and FA metabolism
* deficiency of folate or B12 results in elevated homocysteine levels
* *commercial*: cyanocobalamin
* physiological coenzyme forms: methylcobalamin and 5'deoxyadenosylcobalamin
* synthesized by _intestinal microbiota_ -> NOT present in plants
* breastfed infants of vegan mothers at risk for deficiency -> can be masked by high folic acid intake
## Footnote
pg 932
46
clinical indication of B12
* significant amount of B12 is stored in the body (vital for life)
* anemia (folate recycling is blocked)
* other symptoms: fatigue, glossitis, nerve damage (tingling and numbness in hands and feet), shortness of breath
**pernicious anemia** (severe malabsorption)
* B12 released from food in stomach binds to R-protein -> released by pancreatic enzyme -> binds to intrinsic factor (IF) -> transported through general circulation bound to transcobalamin -> liver -> bile
* severe malabsorption of B12 causes pernicious anemia due to an atrophic gastritis (autoimmune disorder that destroys parietal cells that produce IF)
* partial or total gastrectomy -> loss of IF develops B12 deficiency
## Footnote
pg 933
47
vitamin C -> ascorbic acid
* fuctions as *reducing agent* -> as a coenzyme in *hydroxylation reaction*
* _maintains normal connective tissues and wound healing_
* absorption of dietary non-heme iron from intestine by reducing ferric (Fe3+) to ferrous (Fe2+) form
## Footnote
pg 935
48
scurvy
* sore and spongy gum
* fragile blood vessels
* hemorrhage
* swollen joints
* due to decreased hydroxylation of collagen leading to defective connective tissues
## Footnote
pg 935
49
microcytic anemia
decreased absorption of dietary iron
## Footnote
pg 935
50
choline
* not classified as a vitamin
* synthesis of acetylcholine and phospholipids
* deficiency is rare -> liver damage
* toxicity symptoms: body odor and sweating, salivation, reduced growth rate, low blood pressure, liver damage
## Footnote
pg 937
Scientific Foundations
flashcards
Decks in class (46)
# Cards
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Lecture 1821
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Lecture 1932
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Lecture 2013
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Lecture 2117
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Lecture 2210
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Lecture 2332
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Lecture 2415
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Lecture 258
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Lecture 2636
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Lecture 2743
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Lecture 2929
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Lecture 3223
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Lecture 3339
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Lecture 3429
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Lecture 3550
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Lecture 3627
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Lecture 37/3842
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Lecture 3928
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Lecture 4021
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Lecture 4123
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Lecture 4225
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Lecture 4322
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Lecture 4531
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Lecture 4728
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Lecture 4821
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Lecture 4919
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Lecture 5033
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Lecture 5127
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Lecture 5225
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Lecture 5332
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Lecture 5414
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Lecture 5525
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Lecture 5627
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Lecture 5725
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Lecture 5829
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Lecture 6014
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Lecture 6118
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Lecture 6230
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Lecture 6317
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Lecture 6420
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Lecture 6534
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Lecture 6630
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Lecture 6724
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Lecture 6823
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Lecture 6915
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Lecture 7118
