Lecture 35 Flashcards
Vitamins
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
Q
vitamin B2 -> riboflavin (FMN/FAD)
A
involved in energy metabolism
- FAD and FMN are derived from riboFlavin
- 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)
pg 907
26
Q
riboflavin deficiency
A
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
pg 907
27
Q
vitamin B3 -> niacin (nicotinic acid, nicotinamide, niacinamide, NAD+/NADP+)
A
- 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)
pg 909
28
Q
niacin deficiency -> pellagra
A
- 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
pg 910
29
Q
Hartnup disease
A
- 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
pg 910
30
Q
niacin excess
A
- niacin flush dilates the capillaries and may be painful
- painful flush, hives and rash
- excessive sweating
- blurred vision
- liver damage
- impaired glucose tolerance
pg 911
31
Q
hyperlipidemia treatment
A
- 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)
pg 912
32
Q
niacin food sources and losses
A
- 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
Q
vitamin B5 -> pantothenic acid
A
- 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
pg 914
34
Q
vitamin B6 -> pyridoxal phosphate (PLP)
A
- 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
pg 916-917
35
Q
sideroblastic anemia
A
- 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
pg 918
36
Q
vitamin B7 -> biotin
A
- 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
pg 920
37
Q
biotin deficiency symptoms
A
- depression, lethargy, hallucinations
- numb or tingling sensation in the arms and legs
- red, scaly rash around the eyes, nose and mouth
- hair loss
pg 921
38
Q
vitamin B9 -> folate
A
- 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
pg 923-924
39
Q
serine hydroxymethyltransferase
A
carbon (methyl group off serine) added to purine bases, thymine, S-adenosylmethionine (choline phospholipids, creatine, epinephrine, DNA methylation)
tetrahydrofolate -> N,N-methylene-tetrahydrofolate
pg 925
40
Q
clinical indication of folate deficiency
A
- 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
pg 926-927
41
Q
macrocytic/megaloblastic anemia
A
- 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
pg 926
42
Q
neural tube defect
A
- 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
pg 927
43
Q
inhibitors of folate metabolism
A
chemotherapy, methotrexate (autoimmune diseases supplemented with folinic acid), antibacterial (sulfonamides) and antimalarial (pyrimethamine) drugs
pg 929
44
Q
folate trap (methyl trap)
A
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
pg 930
45
Q
vitamin B12 -> cobalamin
A
- 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
pg 932
46
Q
clinical indication of B12
A
- 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
pg 933
47
Q
vitamin C -> ascorbic acid
A
- 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
pg 935
48
Q
scurvy
A
- sore and spongy gum
- fragile blood vessels
- hemorrhage
- swollen joints
- due to decreased hydroxylation of collagen leading to defective connective tissues
pg 935
49
Q
microcytic anemia
A
decreased absorption of dietary iron
pg 935
50
Q
choline
A
- 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
pg 937
