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IHN: Biochemistry 2 > Vitamin A and Carotenoids Part 2 > Flashcards

Vitamin A and Carotenoids Part 2 Flashcards

1
Q

symmetric cleavage of beta-carotene yields __ is catalyzed by __ and requires __ and __

A

symmetric cleavage of beta-carotene yields 2 retinal is catalyzed by BCO1 and requires oxygen and iron

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2
Q

2 options for retinal from beta-carotene

A
  1. retinal to retinol (by RDH)
  2. retinal into reinoic acid (RALDH)
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3
Q

2 fates of retinol

A
  1. retinol back to retinal (RDH)
  2. retinol to retinyl ester (LRAT)
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4
Q

asymmetric cleavage of beta-carotene yields __ and __ and is __ efficient
catalyzed by __

A

asymmetric cleavage of beta-carotene yields retinal and beta-carotene and is less efficient
catalyzed by BCO2

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5
Q

how is dietary vitamin A distributed to cells?

A

chylomicrons

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6
Q

absorption and circulation of vit A steps

A
  1. chylomicrons take vit A from diet from lymph and send to cardiovascular system
  2. LPL removes FA in RE in chylomicrons to produce retionol and chylomicron remnants
  3. liver processes chylomicron with remaining TG and RE
  4. some RE goes to LDL and VLDL then to circulation
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7
Q

most abundant form of vit A in post-hepatic circulation

A

retinol

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8
Q

stellate cells are liver __ that specialize in __

A

stellate cells are liver fibroblasts that specialize in storing vit A

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9
Q

retinol is transported from __ to __ in liver, where it is esterified by __ and __ and stored as __ in __

A

retinol is transported from parenchymal cells to stellate cells in liver, where it is esterified by LRAT and ARAT and stored as RE in lipid droplets

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10
Q

95% of liver retinoids are stored as __
the rest are stored as __

A

95% of liver retinoids are stored as retinyl esters
the rest are stored as retinol-CRBP

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11
Q

80% of total retinyl esters in the body are stored in __ cells (in the __)

A

80% of total retinyl esters in the body are stored in stellate cells (in the liver)

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12
Q

remaining 20% of RE is stored in

A

adipose tissue

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13
Q

process of getting vit A from stellate cells to systemic circulation

A

stellate cells –> parenchymal cells –> blood

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14
Q

initial distribution of vit A:
distribution of vit A in fasting/postabsorptive state:

A

initial distribution of vit A: chylomicrons (bypass liver bc too much fat)
distribution of vit A in fasting/postabsorptive state: RBP-TTR carries

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15
Q

primary storage organ for RE

A

liver

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16
Q

retinol is secreted from liver bound to

A

RBP or RBP4

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17
Q

RBP is mainly found in __ and functions in

A

RBP is mainly found in liver and functions in mobilization and inter-organ transport of retinol

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18
Q

what controls synthesis of RBP

A

retionic acid (trxn factor)

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19
Q

TTR aka

A

pre-albumin

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20
Q

retinol-RBP-TTR deliver retinol to __ and maintains circulating concentration of retinol in a __ range even with __ vit A intake

A

retinol-RBP-TTR deliver retinol to target organs and maintains circulating concentration of retinol in a narrow range even with no vit A intake

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21
Q

mutation in RBP or TTR causes __ even with __

A

mutation in RBP or TTR causes vit A deficiency even with adequate vit A intake

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22
Q

most abundant form of vit A in
fasting state:
postprandial/fed state:

A

most abundant form of vit A in
fasting state: retinol-RBP
postprandial/fed state: RE in chylomicrons

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23
Q

__ is constant during fed state, so it is a good marker of vit A status

A

retinol-RBP4 is constant during fed state, so it is a good marker of vit A status

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24
Q

food form of vit A:
absorbable form of vit A:

A

food form of vit A: RE
absorbable form of vit A: retinol

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25
Q

how does retinol get into cells?

A

diffusion
NO transporter

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26
Q

retinoid absorption all inclusive

A
  1. dietary RE and carotenes digested
  2. enterocyte absorbs retinol (no transport protein needed)
  3. in enterocyte, retinol –> RE –> chylomicrons
  4. chylomicrons –> lymph
  5. chylomicrons dumped into blood circulation
  6. LPL releases retinol to cells, ultimately leads to chylomicron remnants
  7. liver collects chylomicron remnants and RE from circulation
  8. liver stores RE in stellate cells
  9. in hepatocyte, retinol attached to RBP
  10. retinol-RBP released to plasma, forms complex with TTR
  11. retinol-RBP-TTR transports retinol to cells of target organs
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27
Q

dominant animal food form of vit A
dominant plant food form of vit A

A

dominant animal food form of vit A: RE
dominant plant food form of vit A: carotenoids

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28
Q

absorbable form of vit A is ONLY

A

retinol

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29
Q

carotenoids are absorbed as __ once packed into __

A

carotenoids are absorbed as whole molecules once packed into micelles

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30
Q

__ and __ can enters chylomicrons

A

RE and carotenoids can enters chylomicrons

31
Q

retinol to retinoic acid pathway

A

retinol oxidized to retinoic acid

32
Q

carotenoids to retinoic acid pathway

A

carotenoids cleaved by BCO1+2 to retinal
retinal oxidized to reitinoic acid

33
Q

most retinoic acid (bio active form) is produced by __ and transported by __

A

most retinoic acid (bio active form) is produced by enterocyte and transported by albumin

34
Q

RBP binds to __, absorbs __ into cell which is oxidized to __

A

RBP binds to Stra6, absorbs retinol into cell which is oxidized to retinoic acid

35
Q

Stra6 is found on __
mutation of Stra6 can cause __

A

Stra6 is found on all cell surfaces
mutation of Stra6 can cause vit A deficiency

36
Q

3 sources of retinoic acid

A
  1. RBP-Stra6
  2. RE in chylomicrons
  3. retionic acid in plasma bound to albumin
37
Q

RE in chylomicrons are converted to __ by __, then oxidized to __

A

RE in chylomicrons are converted to retinol by LPL, then oxidized to retinoic acid

38
Q

a fraction of retinoic acid exists in __ bound to __

A

a fraction of retinoic acid exists in plasma blood bound to albumin

39
Q

no vitamin A = __ gene targets

A

no vitamin A = silenced gene targets

40
Q

inside cell, retinoic acid pathway decreased trxn

A
  1. in cell, retinol is oxidized to retinoic acid
  2. CRABP shuttles retinoic acid to nucleus
  3. histone deacetylase enzyme removes acetyl groups –> chromatin condenses –> no trxn
41
Q

inside cell, retinoic acid pathway increased trxn

A
  1. RA-CRABP removes histone deacetylase enzyme from nucleus
  2. RA-CRABP recruits co-activator complex to receptors, RAR and RXR, leads to a loosened, more accessible chromatin
42
Q

during average vit A intake, excretion via

A

urine
some in bile and feces

43
Q

excess vit A intake
__ can’t tolerate, so some vit A reabsorbed with __, most into __

A

excess vit A intake
liver can’t tolerate, so some vit A reabsorbed with bile, most into feces

44
Q

more vit A in system = more enters __

A

more vit A in system = more enters bile

45
Q

vit A (retinoic acid in form of __) can be conjugated with __ to form a water-soluble form, __ which enters __ and is excreted with __

A

vit A (retinoic acid in form of 4-oxo-retinoic acid) can be conjugated with glucouronic acid to form a water-soluble form, 4-oxo-retinoic acid glucouronide which enters bile and is excreted with feces

46
Q

main form of excreted vit A

A

4-oxo-retinoic acid glucuronide

47
Q

vision:
trxn gene expression:

A

vision: 11-cis-retinal
trxn gene expression: all-trans retinoic acid binds RAR, 9-cis-retinoic acid binds RXR

48
Q

RAR and RXR have

A

receptor variants

49
Q

cones vs rods

A

cones: detect color
rods detect: dim light

50
Q

which are more widely distributed (rods or cones)

51
Q

rhodopsin is made of __ and __

A

rhodopsin is made of opsin and 11-cis-retinal

52
Q

__ are concentrated with rhodopsin

A

rods are concentrated with rhodopsin

53
Q

__ produces 11-cis-retinal, not __

A

retinal pigement epithelium produces 11-cis-retinal, not rods

54
Q

retionid metabolism (detecting dim light)

A
  1. retionol-RBP binds to Stra6 and is absorbed into the retinal pigement epithelium cell
  2. retinal pigment epithelium converts all-trans-retinol into –> all-trans-RE –> 11-cis-retinol –> 11-cis retinal
  3. 11-cis-retinal is transferred to rod where it combines with opsin to make rhodopsin
  4. light degrades rhodopsin into opsin and all-trans-retinol
  5. all-trans retinol is trasferred back to retinal pigement epithelium to re-produce 11-cid retinal for anothe cycle
55
Q

phototransduction steps

A
  1. light splits rhodopsin
  2. induces configurational change in transducin
  3. transducin targets PDE which destroys cGMP and cAMP
  4. cGMP gated ion channels close due to decreased cGMP
  5. plasma membrane hyperpolarized
  6. hyper-polarization –> visual signal –> brain
56
Q

no light = plasma mem is
light = plasma mem is

A

no light = plasma mem is depolarized
light = plasma mem is hyperpolarized

57
Q

phototransduction

A

hyperpolarization –> visual signal –> brain

58
Q

activation of rhodopsin = __ cGMP = __ cGMP gated ion channels = __ plasma membrane

A

activation of rhodopsin = decreaed cGMP = closed cGMP gated ion channels = ** plasma membraneyperpolarized

59
Q

vit A mediated regulation of trxn

A
  1. retinoic acid binds RXR or RAR to trigger trxn
  2. co-repressor released from receptor
  3. RAR and RXR dimerize
  4. trxn –> mRNA
  5. translation mRNA –> protein
60
Q

__ binds RXR
__ binds RAR

A

9-cis-retinoic acid binds RXR
all-trans-retinoic acid binds RAR

61
Q

no retinoic acid = __ bound to RAR and RXR = no __

A

no retinoic acid = co-repressor bound to RAR and RXR = no dimerization

62
Q

vit A in growth is essential for

A

embryonic development

63
Q

vit A deficiency in growth can cause

A

fetal resorption or multiple abnormalities

64
Q

vit A deficiency causes __ of immunity

A

vit A causes general impairment of immunity

65
Q

vit A deficiency causes atrophy of (3)
decreases in (5)

A

vit A deficiency causes atrophy of thymus, spleen, and lymph nodes
decreases in CD4 T cells, T cell activation, B-cell growth, antibody response, cytokine production

66
Q

assessments of vit A status

A
  1. liver biopsy: most accurate, too invasive
  2. retinol plasma level: highly regulated by body (liver stores must be depleted to detect)
  3. relative dose response assay (>50% plasma increase = deficiency)
67
Q

primary vit A deficiency

A

inadequate diet, low SES
rare in developing countries

68
Q

secondary vit A deficiency

A

biliary tract disease
pancreatic disease
malabsorption syndrome
liver disease

69
Q

how does alcoholism cause vit A deficiency

A

alcohol affects ALDH which deals with retinol

70
Q

groups at risk for deficiency

A
  • preemies
  • infants, kids, pregnant, lactating in developed countries
  • malabsorption (cystic fibrosis, Crohn’s, meds)
71
Q

only vitamin that can cause toxicity is

72
Q

vit A toxicity is caused by __x RDA

A

vit A toxicity is caused by 10x RDA

73
Q

who is at risk for vit A toxicity

74
Q

signs of vit A toxicity

A
  • teratogenic effects (birth defects)
  • fetal resorption
  • liver damage
  • anorexia
  • dry and itchy skin
  • alopecia
  • reduced bone mineral density
  • bone and muscle pain

IHN: Biochemistry 2 (38 decks)

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