Vitamins Flashcards

1
Q

what are vitamins

A
  • chemically unrelated compounds
  • cannot be synthesised by human body
  • required in diet
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2
Q

fat soluble vitamins

A
  • A, D, E, K.
  • released, transported and absorbed in chylomicrons with dietary fat
  • not readily excreted
  • sig. qts in liver and adipose tissue
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3
Q

good source of folic acid

A
  • leafy, dark green veggies
  • wholegrains
  • beans
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4
Q

function of folic acid

A
  • tetrahydrofolate is the reduced coenzyme form of folate
  • receives 1C fragments from donors
  • synthesis of AA, purine nucleotides, thymidine monophosphate (pyrimidine nucleotide incorporated into DNA)
  • deficiency = cant make DNA = can’t divide
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5
Q

cause of inadequate serum levels of folate

A
  • increased demand (pregnancy, breastfeeding)
  • poor absorption
  • alcoholism
  • treatment with drugs
  • folate-free diet
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6
Q

how long does folate free diet take to cause deficiency

A

few weeks

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7
Q

what are common neural tube defects

A
  • spina bifida
  • anencephaly
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8
Q

how are common NTDs prevented

A
  • adequate nutrition at time of conception as critical folate-dependent development occurs in 1st weeks
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9
Q

biomedical functions of vitamin B12

A
  • remethylation of Hcy to methionine
  • isommerisation of methylmalonyl CoA
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10
Q

one cause of neurological manifestations of B12 deficiency?

A
  • methylmalonyl cOa produced during degradation of fatty acids
  • if left un-isomerised, unusual branched FA accumulate + become incorporated into cell membrane, including those of CNS
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11
Q

sources of B12

A
  • only micro-organisms, not made in plants
  • liver
  • red meat
  • fish
  • eggs
  • dairy products
  • fortified cereal
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12
Q

Explain the folate trap hypothesis

A
  • methionine synthase uses B12 as coenzyme when converting 5-methylTHF into other forms of THF
  • deficiency = folate cant be converted and is trapped = decrease in other forms of THF
  • other forms required for purine and TMP synthesis = symptoms of megaloblastic anaemia
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13
Q

which cells are effects of cobalamin deficiency most pronounced?

A
  • rapidly dividing cells:
  • erythropoietic tissue
  • mucosal cells
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14
Q

how long does cobalamin deficiency symptoms take to show

A
  • several years as significant amounts stored in body IF due to intake
  • more quickly if due to absorption
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15
Q

which test evaluates b12 absorption

A

schilling test

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16
Q

increased levels of what in blood indicate b12 deficiency

A

methylmalonic acid

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17
Q

How is cobalamin absorbed by the body?

A
  • released from food in acidic environment of stomach
  • free b12 binds to glycoprotein, transp to intestine
  • pancreatic enzyme releases from R-protein, b12 binds to IF
  • b12-IF complex travels through intestine, binds to cubulin receptor on surface of mucosal cells in ileum
  • b12 transp into mucosal cell and subsequently general circulation.
  • carried by binding protein transcobalamin
  • taken up and stored by liver, released in bile, reabsorbed in ileum
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18
Q

cause of malabsorption of cobalamin in elderly

A

reduced secretion of gastric acid (achlorydia)

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19
Q

what is pernicious anaemia

A

severe malabsorption of cobalamin

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20
Q

common cause of pernicious anaemia

A
  • autoimmune destruction of gastric parietal cells that absorb IF
  • partial/total gastrectomy become IF deficient and therefore b12 deficient.
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21
Q

effects of cobalamin deficiency

A
  • anaemic (folate recylcing impaired)
  • neuropsychiatric symptoms as disease develops. CNS effects irreversible
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22
Q

treatment of pernicious anaemia

A

lifelong treatment of
- high dose oral b12 or
- IM cyanocobalamin

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23
Q

why does b12 supplementation work

A
  • approx 1% cobalamin uptake is by IF-independent diffusion
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24
Q

active form of vitamin C

A

ascorbic acid

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25
Q

Function of vit C

A
  • act as reducing agent.
  • coenzyme in hydroxylation reactions. e.g. hydroxylation of proline and lysyl residues in collagen.
  • thus, required for maintenance of normal connective tissue + wound healing.
  • facilitates absorption of dietary non-haeme iron from intestine by reducton of fe3+ to fe2+
  • antioxidant
  • forms collagen, bile acids, epinephrine and steroid hormones
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26
Q

Vit C deficiency

A
  • scurvy; bleeding gums, haemorrhage, fatigue, bone, joint, teeth
  • can be explained by defective connective tissue
  • also causes microcytic anaemia
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27
Q

what is vit b6 a collective term for

A
  • pyridoxine, pyridoxal and pyridoxamine; all derivatives of pyridine
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28
Q

which b6 is found in plants

A
  • pyridoxine
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29
Q

which b6 is found in animal derived food

A

pyridoxamine and pyridoxal

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30
Q

biochemical function of b6 supp

A
  • precursors to PLP (coenzyme)
  • e.g. transulfuration of Hcy to cysteine
  • transamination
  • deamination
  • decarboxylation
  • condensation
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31
Q

clinicals b6 deficiency

A
  • isoniazid used to treat TB induces b6 defic. bc forms inactive derivative with PLP.
  • administered in conjunction w b6 supplementation
  • dietary deficiencies in newborns, women taking oral contraceptive, alcoholism
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32
Q

b6 toxicity

A
    • excess of 400x RDA causes sensory neuropathy
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33
Q

what is thiamine

A

vit b1

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34
Q

active form of b1 and how is it formed

A

thiamine pyrophosphate TPP formed by transfer of pyrophosphate grp from ADP

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35
Q

biochemical functions of b1

A
  • formation/degradation of alpha ketols
  • oxidative decarboxylation of a-keto acids
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36
Q

beri-beri + classification

A
  • thiamine-deficiency syndrome found inn areas where polished rice is major comp of diet
  • dry: peripheral neuropathy esp in legs
  • wet: oedema bc of dilated cardiomyopathy
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37
Q

Wernicke-korsakoff syndrome

A
  • dietary insufficiency/impaired intestinal absorption of thiamine
  • mental confusion
  • gait ataxia
  • nystagmus
  • opthalmoplegia: paralysis of eye muscles
  • wernicke encephalopathy
  • memory problems+ hallucinations with korsakoff dementia
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38
Q

why does b1 deficiency affect CNS

A
  • oxidative decarboxylation of pyruvate and AKG is decreased
  • less ATP produced
  • impaired cellular function
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39
Q

what is niacin

A

vit b3.
niacin/nicotinic acid

40
Q

biologically active coenzyme forms of b3

A

NAD+ and its phosphorylated derivative NADP+

41
Q

distribution of niacin

A
  • unrefined and enriched grains and cereal, milk and lean meats (especially liver)
42
Q

what does niacin deficiency cause

A

-pellagra; disease involving skin, GIT and CNS.
- symptoms progress through 3 Ds;
- dermatitis (photosensitivity)
- diarrhoea
- dementia
- death if untreated
- Hartnup disorder (defective absorption of tryptophan) results in pellagra like symptoms

43
Q

what type of diet causes pellagra

A

corn based as low in niacin and tryptophan

44
Q

how is niacin used to treat hyperlipidemia

A
  • niacin at 1.5g/day strongly inhibits lipolysis at adipose tissue
  • reduces free FA circulating
  • reduces TAG prod and therefore VLDL
  • LDL derived from VLDL so also red
  • particularly useful in type 11b hyperlipoporteinemia
  • high naicin doses causes flushing, taking aspirin 30 mins prior can reduce effects
45
Q

name of vitamin b2

A

riboflavin

46
Q

biologically active forms of b2

A
  • flavin mononucleotide FMN
  • FAD formed by AMP moiety from ATP to FMN
47
Q

biochemical function of b2

A
  • both bind tightly to flavoenzyes can oxidise or reduce substance
  • e.g. NADH dehydrogenase (FMN)
    succinate dehydrogenase (FAD)
48
Q

b2 deficiency

A

not associated w/ major human disease, but accompanies other vit deficiencies
- symptoms; dermatitis, cheilosis glossitis

49
Q

what is b7 known as

A

biotin

50
Q

biochemical imp of biotin

A
  • coenzyme in carboxylation reactions: carrier of activated carbon
  • coenzyme in gluconeogenesis+ citric acid cycle, fatty acid synthesis and propyl coenzyme synthesis
51
Q

deficiency of biotin leads to

A
  • anaemia
  • loss of appetite
  • hair loss
  • nausea
  • dermatitis
  • depression
  • halucinations
  • muscle pain
52
Q

sources vit b7

A
  • widely distributed; liver, kidney egg yolk, tomatoes, grain
53
Q

another name for b5

A

pantothenic acid

54
Q

sources b5

A
  • eggs
  • liver
  • yeast
55
Q

active states vit b5

A

CoA; central molecule involved in all metabolisms eg dehydrogenation of pyruvate + AKG

56
Q

natural form of vit A

A

retinol

57
Q

what do the retinoids include

A
  1. retinol: storage form of Vit A, found in animal tissues. is a primary alcohol
  2. retinal: aldehyde derivative of retinol when oxidised
  3. retinoic acid: acid derived from oxidation of retinal. cannot be produced in body
  4. beta-carotene: plant foods contain it.
    - AKA provitamin A.
    - oxidatively cleaved in intestine to give 2 retinal molecules.
    - has antioxidant activity
58
Q

sources of vitamin A

A
  • liver
  • kidney
  • cream
  • butter
  • egg yolk
  • yellow, orange, daark green vegertables and fruits good sources of carotenes
59
Q

vit A absorption and transport to liver

A
  • retinyl esters -> retinol and FFA
  • b-carotene -> retinal -> reduced to retinol
  • both these retinols re-esterified in enterocytes using fatty CoA
  • secreted as component of chylomicrons in lymphatic system.
  • chylomicron remnants containing retinyl esters taken up by and stored in liver
60
Q

release from liver

A
  • retinol binding protein complexed with transthyretin transports retinol through blood
  • binds to transp protein on surface of peripheral tissue cells, allows retinol to enter
61
Q

retinoic acid mechanism of action

A
  • retinol oxidised to retinoic acid
  • binds to receptor acid receptors RAR in nucleus
  • retinoic acid-RAR complex binds to response elements on DNA and regulates RNA synthesis
  • allows control of specific protein eg keratin
62
Q

functions of vit A

A
  • vision maintenance (retinoic acid not involved)
  • epithelial cell maintenance - differentiation - mucus secretion - immune syst
  • reproduction; supports spermatogenesis and prevents fetal resorption in females (retinoic acid not involved)
  • bone growth
63
Q

describe visual cycle vit A

A
  • 11-cis retinal + opsin -> rhodopsin
  • light + rhodopsin -> all-trans retinal + opsin
  • all-trans retinal -> all trans retinol -> all-trans retinyl esters -> 11-cis retinol -> 11-cis retinal
64
Q

effects of vit A deficiency

A
  • earliest sign: nyctalopia (night blindness)
  • prolonged deficiency = permanent loss of visual cells
  • severe deficiency xerophthalmia ; untreated = blindness
65
Q

what is xerophalthamia

A
  • pathologic dryness of conjunctiva and cornea caused in part by inc keratin synthesis
  • untreated -> corneal ulceration -> blindness due to formation of opaque scar tissue
66
Q

which vit A is used to treat mild acne + skin aging

A

all-trans retinoic acid (tretinoin) oral too toxic

67
Q

what is oral tretinoin used for

A

acute promyelocytic leukemia

68
Q

what is isotretinoin used for

A
  • severe cystic acne.
  • is teratogenic, should be avoided in women of child-bearing capacity
69
Q

how is psoriasis treated

A

oral synthetic retinoid

70
Q

excess of vitamin A

A
  • hypervitaminosis A
  • skin dry and pruritic ( decreased keratin)
  • liver enlarged - can become cirrhotic
  • CNS-> rise in intracranial pressure can mimic symptoms of brain tumour.
  • decreased bone mineral density + increased risk of fractures
  • teratogenesis in pregnant women
71
Q

which retinoid functions as a hormone

A

retinol

72
Q

active form of vitamin E

A

alpha-tocopherol

73
Q

function of vit E

A
  • antioxidant in prevention of nonenzymic oxidations, eg oxidation of LDL and peroxidation of polyunsaturated FA
74
Q

effect of vit C on vit E

A

C regenerates active vit E

75
Q

sources of vit E

A
  • vegetable oils rich source
  • liver and eggs moderate source
76
Q

vit E deficiency

A
  • newborns can obtain from breast milk/supplements to prevent haemolysis and retinopathy
  • in adults, usually due to defective lipid absorption/transport
  • abetalipoproteinemia caused by defecr in formation of chylomicrons result in vit E deficiency
77
Q

what is the least toxic fat sol vitamin

A

vit E

78
Q

active molecule of vitamin D

A
  • calcitriol
79
Q

vit D distribution

A
  • collagen synthesis intermediate converted to vit D3 in dermis + epidermis when exposed to sunlight, transp to liver by vit d-binding protein
  • diet; vit d2 found in plants and vit d3 found in animal tissues. dietary vit D packaged into chylomicrons
80
Q

how is vit d formed

A
  • vit d2 + d3 converted to calcitriol by 2 sequential hydroxylation reactions
  • 1st in liver forms calcidiol
  • 2nd in kidneys form calcitriol
81
Q

functions of vit D

A
  • maintain adequate ca2+ serum levels
  • inc ca2+ mobilisation from bone
  • inc renal resorption ca2+
  • dec renal excretion of ca2+
  • inc intestinal absorption of ca2+
82
Q

how does vit d increase intestinal absorption of calcium

A
  • calcitriol binds to cytosolic receptor in intestinal cell and interacts w/ response elements on DNA
  • increases gene expression of calbindin
83
Q

sources of vit D

A
  • fatty fish
  • liver
  • egg yolk
84
Q

Vit D deficiency

A

diet causes:
- rickets in children - continual formation of collagen matrix but not mineralisation - soft and pliable bones
- osteomalacia in adults - demineralisation of bones increases susceptibility to fracture -bow legs

mutation in vit d receptor causes hereditary vit d-deficient rickets

85
Q

Renal osteodystrophy causes, effects and treatment

A
  • caused by chronic kidney disease
  • decreased vit D formation, hyperphosphatemia and hypocalcemia
  • low ca2+ = increase in PTH -> associated bone demineralisation
  • treated with vit d supplementation + PO43- reduction therapy
86
Q

what is hypoparathyroidism + treatment

A
  • lack of PTH causes hypocalcemia and hyperphosphatemia as PTH increases phosphate excretion
  • treated with vit D
87
Q

Vit D toxicity symptoms

A
  • loss of appetite
  • nausea
  • thirst
  • weakness
  • hypercalcemia - ca2+ deposits in soft tissue (metastatic calcification)
  • excess vit d produced in skin is converted to inactive form so doesnt cause toxicity
88
Q

principal role of vit K

A
  • coenzyme in carboxylation of glutamic acid residues to gamma-carboxyglutamate (Gla) in post-translational protein modification
  • req y-glutamylcarboxylase, O2, CO2, hydroquinone form of vit K (gets oxidised to epoxide form)
  • Gla residues also used to form osteocalcin + matrix Gla protein in bones
89
Q

active forms of vit K

A
  • plants as phylloquinone (K1)
  • intestinal bacteria as menaquinone (K2)
  • menadione (synthetic form of vit K) can be converted to K2
90
Q

what can inhibit formation of Gla residues

A

warfarin - synthetic analog of vit K (inhibits VKOR, enzyme req to regenerate functional form hydroquinone form of vit K

91
Q

what blood clotting proteins is vit k involved in formation of

A
  • prothrombin
  • FVII
  • FIX
  • FX
92
Q

vitamin K sources

A
  • cabbage
  • kale
  • spinach
  • egg yolk
  • liver
  • intestinal bacteria
93
Q

vitamin K deficiency

A
  • unusual as adequate amounts in diet and bacteria
  • decrease in bacterial gut population eg by antibiotics -> leads to hypoprothrombenima -> bleeding tendency therefore may need vit K supplementation
    cephalosporin antibiotics have warfarin-like mechanism, inhibits VKOR
  • deficiency can also affect bone health
94
Q

why can newborns have vit K deficiency

A
  • sterile intestines + breastmilk provides only 1/5th of req amount
  • therefore single intramuscular dose as prophylaxis against haemorrhagic disease of the newborn
95
Q

Vit K excess

A
  • prolonged admin of large doses of menadione can cause haemolytic anaemia and jaundice in infants due to RBC membrane damage