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IHN BIOCHEMISTRY FINAL > Quiz 5: Iron > Flashcards

Quiz 5: Iron Flashcards

1
Q

__ people have IDA

A

0.5 billion people have IDA

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2
Q

anemia is a disease of __

A

anemia is a disease of poverty

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3
Q

anemia = problems delivering __ and reabsorbing __

A

anemia = problems delivering O2 and reabsorbing CO2

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4
Q

iron deficiency causes

A
  1. abnormal cognitive and psychomotor development (altered NT metabolism)
  2. increased rates of premature delivery and perinatal mortality
  3. decreased work performance, decreased effort
  4. impaired immune response and thermogenesis
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5
Q

why does iron deficiency cause abnormal cognitive and psychomotor development

A

altered NT metabolism

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6
Q

iron is essential in physiology due to its capacity to exist in

A

several oxidation states

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7
Q

2 oxidation states of iron

A

ferrous (Fe2+)
ferric (Fe3+)

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8
Q

iron is a constituent of many proteins involved in transport and metabolism of __

A

iron is a constituent of many proteins involved in transport and metabolism of oxygen

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9
Q

iron is a __ mineral

A

iron is a trace mineral

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10
Q

main iron in circulation

A

ferric (Fe3+)

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11
Q

absorbable form of iron

A

ferrous (Fe2+)

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12
Q

iron solubility problem
__ soluble at neutral pH + reactive with oxygen
__ not soluble at neutral pH, forms ferrihydroxides with water

A

iron solubility problem
Fe2+ (ferrous) soluble at neutral pH + reactive with oxygen
Fe3+ (ferric) not soluble at neutral pH, forms ferrihydroxides with water

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13
Q

what does ferric iron require to move

A

transferrin (carrier protein)

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14
Q

body iron compartments

A
  1. most in circulation as hemoglobin
  2. 95% bound with ferritin (stored iron)
  3. rest = iron-containing enzymes or bound to transferrin
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15
Q

hemoglobin
myoglobin
ferritin
transferrin

A

hemoglobin: transport O2 in blood
myoglobin: muscle
ferritin: storage
transferrin: transfer to cells

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16
Q

food source

A

oysters
beans
chocolate
fortified cereals
lentils
spinach

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17
Q

RDA increased in

A

females bc menstruation
pregnancy (baby needs blood and circulatory system)

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18
Q

iron supplements should be taken with

A

orange juice bc vit C

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19
Q

iron UL

A

causes GI side effects (nausea and constipation)
bc iron is insoluble in gut secretions

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20
Q

3 determinants of iron absorption

A
  1. iron content in diet
  2. bioavailability
  3. absorption capacity of enterocyte
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21
Q

3 forms of dietary iron

A
  1. heme iron
  2. non-heme
  3. supplements
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22
Q

largest component of dietary iron is

A

non-heme iron (plants)

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23
Q

non-heme iron is usually found

A

attached to protein

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24
Q

non-heme iron
plant sources
animal sources
other sources

A

non-heme iron
plant sources: metalloproteins (ferritin), soluble iron, non-functional iron (structure or storage with phytates)
animal sources: ferritin and hemosiderins (meat), phosphoritin (egg yolk), lactoferrin (milk)
other sources: contaminants (ferric oxides and hydroxides)

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25
Q

heme iron major sources

A

hemoglobin and myoglobin

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26
Q

increase heme iron = __ bioavailability for non-heme iron (meat factor)

A

increase heme iron = increased bioavailability for non-heme iron (meat factor)

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27
Q

heme is rapidly released from __ during digestion

A

heme is rapidly released from hemoglobin during digestion

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28
Q

what factors interfere with heme absorption?

A

NONE

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29
Q

absorption of heme iron
non-heme iron

A

heme iron = 10-35%
non-heme iron = < 10%

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30
Q

absorption of iron steps Fe2+ and Fe3+ path

A
  1. bound heme or non-heme iron digested to Fe3+ and Fe2+
  2. Fe3+ to Fe2+ (DcytB)
  3. DMT1 brings Fe2+ and H+ in
  4. H+ out via NHE
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31
Q

absorption of iron as heme

A
  1. myoglobin + Hg = heme
  2. heme absorbed by hcp1
  3. heme –> Fe2+ (heme oxygenase)
  4. Fe2+ bound by ferroportin
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32
Q

increased iron in blood = __ ferroportin

A

increased iron in blood = decreased ferroportin

33
Q

what does hephaestin do

A

turn Fe2+ to Fe3+

34
Q

we can’t have Fe2+ in circulation
how do we fix this

A

ferroportin is attached to hephaestin
hepahestin turns Fe2+ to Fe3+
transferrin binds to carry Fe3+ around

35
Q

hephaestin requires __

A

Cu

36
Q

SO __ deficiency causes issues with iron

A

SO Cu deficiency causes issues with iron

37
Q

enhancers of iron absorption

A
  1. sugars
  2. acids
  3. low pH
  4. mucin
  5. meat
  6. fish
38
Q

inhibitors of absorption of iron

A
  1. high pH
  2. polyphenols (coffee)
  3. oxalic acid (spinach)
  4. phytic acid (grain)
  5. phosvitin (egg yolk)
  6. divalent cations (Ca, Zn, Ca)
39
Q

DMT1 =

A

divalent metal transporter 1

40
Q

what type of transporter is DMT1

A

symporter Fe2+, H+

41
Q

low iron = __ trxn of DMT1 gene in enterocytes

A

low iron = increased trxn of DMT1 gene in enterocytes

42
Q

release of iron from heme

A

heme –> iron (enzyme: heme oxygenase + cytochrome P450 reductase)
requires NADPH, O2, releases biliverdin + carbon monoxide

iron –> ferritin or to export
biliverdin –> bilirubin (biliverdin reductase)
carbon monoxide (VERY TOXIC) –> soluble guanylyl cyclase

43
Q

heme degradation is higher in what tissues

A

macrophages in spleen
Kupffer cells

44
Q

3 types of iron-containing proteins

A
  1. heme proteins
  2. iron-sulfur proteins
  3. non-heme, non-iron-sulfur proteins
45
Q

iron containing heme proteins

A

hemoglobin
myoglobin
cytochrome c

46
Q

iron-sulfur proteins

A

NADH dehydrogenase
cytochrome c reductase

47
Q

non-heme, non-iron-sulfur proteins

A

tyrosine hydroxylase
fatty acid desaturases

48
Q

biological functions of iron

A
  1. binding site for gases
  2. regulates enzyme activity
  3. modulate gene trxn and post-trxn modifications
49
Q

hemoglobin binds __ O2
myoglobin binds __ O2
hemoglobin transports O2 in __ where it exchanges O2 to myoglobin for transport in __

A

hemoglobin binds 4 O2
myoglobin binds 1 O2
hemoglobin transports O2 in blood where it exchanges O2 to myoglobin for transport in muscle

50
Q

sickle cell disease is a mutation in B-globin gene that causes __

A

sickle cell disease is a mutation in B-globin gene that causes hemoglobin protein aggregation

51
Q

4 proteins of iron transport

A

transferrin
haptoglobin
ferritin
lactoferrin

52
Q

transferrin is major __ protein for Fe transport
made in __

A

transferrin is major plasma protein for Fe transport
made in liver

53
Q

__ of transferrin is normally saturated with iron

A

1/3 of transferrin is normally saturated with iron

54
Q

transferrin receptor requires __ Fe bound

A

transferrin receptor requires 2 Fe bound

55
Q

transferrin receptor is 2 homodimers bound by __ bridge that binds 2 saturated __

A

transferrin receptor is 2 homodimers bound by disulfide bridge that binds 2 saturated transferrin Fe3+

56
Q

2 transferrin receptors

A

Tfr1: iron uptake, expressed in ALL cells
Tfr2: senses systematic iron status, liver and erythroid precursors

57
Q

3 sites for storage of iron bound to ferritin

A

liver
spleen
skeletal muscle

58
Q

storage form of iron

A

hemosiderins

59
Q

endocytosis of iron complex + transferrin

A
  1. each Tfr binds 2 Tf molecules
  2. uptake, endocytosis, Fe3+ to Fe2+ (Steap3)
  3. released Fe2+ to exit cytosol (DMT1), release Hg and ferritin
  4. apotransferrin-Tfr complex recycled to cell surface
  5. Apo-Tf released back into circulation
60
Q

why is endocytosis of iron so complex?

A

bc iron can cause a lot of damage (it is very reactive) if not handled properly

61
Q

2 types of iron regulation

A
  1. cellular (trxn and post-trxn regulation)
  2. systemic (hepcidin-ferroportin axis)
62
Q

trxn regulation:
low iron = increased __ and __
high iron = increased __

A

trxn regulation:
low iron = increased DMT1 and Tfr
high iron = increased ferritin

63
Q

iron responsive elements

A

nucleotides in ferritin mRNA that control post-trxn regulation

64
Q

iron-regulatory proteins

A

cytosolic proteins that interact with IREs to modulate translation

65
Q

low iron trxn modifications

A
  1. in low Fe, 1 Fe binds 5’ UTR –> blocks ferritin translation
  2. 1 Fe binds 3’ UTR –> increases transferrin receptor translation (Tfr)
66
Q

high iron trxn modifictions

A

no binding
ferritin made more
fragile, low transferrin receptors

67
Q

iron deficiency = __ transferring receptors

A

iron deficiency = more transferring receptors

68
Q

iron overload = Tfr messenger __ = __ = decreased __

A

iron overload = Tfr messenger weak = degraded = decreased Tfr

69
Q

iron concentration in diff body regions

A

GI tract > skin > urine

70
Q

which cell defines iron homeostasis?

A

macrophages and enterocytes

71
Q

ferritin mediated export of iron
macrophages

A
  1. macrophage processes RBC (tons)
  2. Fe2+ leaves in ferroprotin
  3. Fe2+ –> Fe3+ (cell linked ceruloplasmin)
  4. circulation
72
Q

ferritin mediated export of iron
enterocyte

A
  1. ferritin enters cell
  2. Fe 2+ leaves through ferroportin
  3. Fe2+ –> Fe3+ (hephaestin: on cell)
73
Q

low iron sensing

A
  1. Tfr2 in liver senses low iron
  2. no hepcidin synthesis
  3. decreased plasma iron (Fe-Tf)
74
Q

high iron sensing

A
  1. high iron sensed by Tfr2
  2. increased plasma Fe-Tf
  3. increased hepcidin released
  4. hepcidin binds ferroportin in enterocyte + macrophage
  5. destroy proteinn, no more ferroportin
  6. Fe in enterocyte is stuck, stays 5 days then to feces
  7. macrophage retains iron for as long as needed
75
Q

iron deficiency affects __ capacity
anemia affects __ capacity

A

iron deficiency affects tissue oxidative capacity
anemia affects oxygen carrying capacity

76
Q

BOTH iron deficiency and anemia cause

A
  1. abnormal cognitive development (altered NT metabolism)
  2. increased premature deliveries
  3. decreased work performance
  4. impaired immune response
77
Q

groups at risk

A
  1. infants
  2. pregnant women
  3. low SES
  4. elderly
  5. cancer pts
  6. GI diseases
78
Q

anemia = __ conc in blood is low = decreased __ capacity of __
also decreased circulating __

A

anemia = hemoglobin conc in blood is low = decreased oxygen carrying capacity of RBC
also decreased circulating RBC

79
Q

hypochromic microcytic anemia of iron deficiency =

A

small RBC with narrow rim of peripheral hemoglobin

IHN BIOCHEMISTRY FINAL (15 decks)

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