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

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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

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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

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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

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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

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6
Q

retinol and retinal

A

reproduction (normal levels)

  • supports spermatogenesis
  • normal fetal development (prevents fetal resorption)

pg 882

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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
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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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