Iron Flashcards

1
Q

what is heme

A

heme iron is a metalloporphyrin ring with Fe in the middle

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2
Q

heme synthesis

A

glycine + succinyl CoA +(PLP) reason why low Hb can be B6 def
+ (ferrochelatase) to incorporate Fe+2
= heme

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3
Q

Fe absorption depends on

A

form of iron:
food - heme or non-heme
form of non-heme - ferrous+2 or ferric +3

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4
Q

3 general steps of Fe absorption

A
  1. uptake at BBM
  2. transport across cell
  3. transport across BLM to plasma
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5
Q

non-heme absorption

A
  1. bound nonheme iron is broken down by HCl
  2. Fe+3 reductase to Fe+2
  3. Fe+2 uptake by divalent metal transporter 1 (DMT1) into cell
  4. Fe+2 binds PCBP2 (binding protein) in cell for transport in cytosol, used in cell OR, stored as ferritin
  5. ferroportin transports iron across BLM. coupled oxidation with hephaestin Cu+-> Cu+2 and Fe+2-> Fe+3
  6. apotransferrin binds to Fe+3 in blood = transferrin-Fe+3 (transport form in blood)
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6
Q

heme Fe absorption

A
  1. Mb and Hb broken down by HCl
  2. heme uptake into HCP1 (heme carrier protein 1). Free heme absorbed into cell
  3. heme oxygenase breaks down heme = protoporphyrin + Fe+2
  4. PCBP2 bound Fe+2
  5. functional use in cell or stored as ferritin
  6. ferroportin transports across BLM, coupled with Cu+ -> Cu+2 and hephaestin = Fe+3
  7. apotransferrin and Fe+3 = transferrin for transport in blood
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7
Q

enhancers of non-heme Fe absorption

A

vitamin c- reduce Fe+3 to Fe+2
food acids (citrate)
fructose
MFP factor: meat/fish/poultry have actin, mysoin digestive products- has to be contractile proteins, includes shellfish and clams
maybe: CYS-peptide or aa HIS, CYS
mucin: lining of stomach and small intestine (natural chelator unless GI problems/malabsorption)

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8
Q

inhibitors of non-heme absorption

A

Polyphenols (tannins in coffee, tea)
Oxalic acid (e.g. spinach)
Phytate [prefers Zn2+]
Phosvitin (egg yolk)
Calcium

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9
Q

Fe absorption step 1 (3 parts)

A

a) heme: released from Hb or Mb
transported across BBM by HCP1 -> inside cell FE+2
b) Fe+2 absorbed by DMT1, inside cell Fe+2
c) Fe+3 either:
i. converted to Fe+2 in lumen
ii. combines w mucin and binds to integrin to be absorbed, when inside cell changed to Fe+2

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10
Q

transport across enterocyte and BLM step 2&3

A
  1. Fe+2 transported to BLM by ligands (mobilferrin)
  2. at BLM, Fe+2 exits through ferroportin
    - Fe+2 to Fe+3 conversion so it can combine w transferrin in plasma
    - copper enzyme hephaestin needed to couple oxidation
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11
Q

how does liver control Fe absorption

A

liver protein- hepcidin released when stores are adequate (sensed as diferric transferrin entering liver)

decrease intestinal iron absorption by decreasing ferroportin- bind to ferroportin and degrade
= Fe not released into blood

mutation in hepcidin can prevent control

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12
Q

transport form of iron

A

Fe+3 bound to apotransferrin = transferrin

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13
Q

receptor for iron

A

at tissues where iron is used or stored TfR transferrin REceptor binds transferrin and pulls into cell
controlling TfR on membranes = control tissue uptake

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14
Q

what does high TfR in plasma mean

A

to be excreted, high levels means low iron stores, apotransferrin can be reused

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15
Q

Fe exit from cells that aren’t enterocytes

A

need Cu enzyme “ferroxidase” to oxidize iron to ferric

enterocyte, hephaestin = other cells, ceruloplasmin

Fe+2 and Cu+2 = Fe+3 and Cu+1

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16
Q

plasma ferritin exiting from stores

A

ferritin (apoferritin and iron) = cell storage of iron as Fe+3

small but constant leak out of cells, for every 10mg Fe in storage = 1mch/L plasma ferritin Fe

healthy man has 1000mg iron stored = 100mch/L plasma ferritin

women: 500mg = 50mcg/L plasma ferritin

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17
Q

Fe cycling

A

RBC synthesis: proerythroblasts differentiate into erythrocytes in marrow
-availability of Hb limiting factor in RBC size and number
erythrocytes circulate 120days = functional Fe (not transport)
in reticuloendothelial cells (spleen), old RBCs disassembled, remove Fe - efficient

overall efficient use/reuse of Fe without external losses of blood, adults need to replace 1mg/ day

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18
Q

functional form of Fe

A

hemoglobin in RBC

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19
Q

what is a measure of Fe storage

A

plasma ferritin /leakage
1mcg/L = 10mg Fe stored

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20
Q

where is storage of Fe highest

A

reticuloendothelial cells (spleen)

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21
Q

4 functions of Fe

A
  1. Hb and Mb
    - each RBC has millions of Hb molecules
    - heme synthesis needs glycine, succinyl CoA, PLP, Zn-enzyme, final step: Fe+2 + protoporphyrin ring = heme
    - attach globin
  2. cytochromes (contain heme) = ETC
  3. other heme enzymes (catalase)
  4. non-heme enzymes
    - prolyl hydroxylase in collages synthesis (cross-link) PRO -> OHproline, requires vit C to regenerate Fe+2 in enzyme
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22
Q

non-heme food sources

A

all plant sources, eggs, dairy, 60% of MFP
enriched flour products or cereals

23
Q

heme food sources

A

different meats have diff heme %, average 40%

beef 62%
lamb 57%
pork 49%
poultry 39%
fish and seafood 13%
organ meats 45%

24
Q

what form of non-heme iron is stable

A

oxidized, Fe+3
fortified foods use this, Fe+2 might cause peroxidation

supplements: can add Fe+2

25
Setting the EAR
replace losses and maintain stores
26
basal losses of iron
1 mg Fe for 70kg person'
27
menstrual blood losses
additional 0.5mg Fe/ day during cycle
28
DRI panel assumed what rate of absorption
18% from a mixed diet, assumes low stores to be cautious
29
if a man loses 1.08mg Fe/day, how much iron from food does he need
6 mg Fe from food bc 18% absorption =EAR
30
a woman 18-50yo no oral contraceptive use, what are the sources of loss
basal loss of 0.89mg + menstrual loss (avg over 28 days) of 0.51mg = 1.4mg/day == needs to eat 8.1mg Fe to replace these losses = EAR
31
RDA Fe
Men and post-menopausal women: 8mg women 18-50yo: 18mg women on OC: 10.9mg
32
how to classify iron adequacy with EAR and RDA
less than EAR = prob inadequate over RDA = prob adequate between = possibly inadequate important for iron bc many women might not need 18mg, should DV be 18mg??
33
lacto-ovo veg bioavailability in diets
x2 Fe
34
blood donation consideration of losses
consider Fe supplement bc body losses high each 500mL blood = 200mg iron minimum most women have iron stores below 500mg one donation / year = 0.6mg/day over the year (avg) need to ear 3.33mg extra Fe/day assuming 18% absorption all year to make up the loss
35
long distance runner
foot strike hemolysis so need more Fe
36
what percentile is RDA set at?
usually 2 SD of EAR but that assumes normal distribution iron loss is not normal RDA= 97.5th percentile, SD much larger
37
how much iron does a blood donor vegetarian runner need
w or m? M: RDA = 10.9 x2(veg) donor = 3.33 mg/day running= more = over 25mg
38
measuring iron status 3 steps
1. look at normal values for that measure 2. note 3 major stages of Fe def, after early negative Fe balance 3. shaded boxes indicate best test for that stage
39
4 measures for iron status
stores: marrow iron, plasma ferritin, serum transferrin receptor nu,bers transport: plasma iron, transferrin saturation, transferrin binding capacity abnormal metabolite: erythrocyte protoporphrin or Zn-protoporphrin function: erythrocytes containing Hb
40
what is tested for stage 1
IRON DEPLETION: iron stores, circulating, erythron iron - reticuloendothelial marrow iron - transferrin iron binding capacity - plasma ferritin - iron absorption %
41
what is tested for stage 2
IRON DEFICIENT ERYTHROPOIESIS: circulating iron and erythron iron - plasma iron - transferrin saturation % - sideroblasts % - erythrocyte protoporphyrin
42
what is tested for stage 3
IRON DEFICIENT ANEMIA: erythron iron - erythrocytes - microcytic hypochromic
43
TIBC
transferrin or total iron binding capacity amount of transferrin available to bind iron
44
transferrin saturation
% of Fe binding sites occupies by Fe
45
what's happening in stage 1
iron depletion body attempts to increase absorption efficiency decreased stores: less marrow iron, less plasma ferritin liver makes more apo transferrin in attempt to increase Fe transport to cells (signal = low hepcidin) more transferrin receptors as cell attempts to increase intracellular Fe
46
what happens in stage 2
iron de erythropoiesis less transport of Fe = inadequate stores, tissues need Fe begin to show biochem abnormalities decreased transport: low plasma iron and % transferrin saturation biochem abnormalities: protoporphyrin found in RBC = heme lacls iron, binds Zn instead - fewer sideroblasts (bone marrow erythroblasts) - Hb low but still in normal range lower IQ in children
47
what happens in stage 3
iron def anemia microcytic hypochromic anemia Hb now below normal and clinical signs- hematocrit and Hb less than 130g/L Men or less than 120g/L Women Low stores, ↑ absorption efficiency, less transported as more needed in cells, ↓ function
48
children symptoms of iron def
pallor, listlessness, behavioural disturbance, cognitive difficulties, short attention span
49
adults iron def symptoms
impaired work performance and productivity
50
anemia Fe def symptoms
extreme fatigue, weak, pale, chest pain, shortness of breath, cold hands and feet, headache, dizzy, light headed, inflammation of tongue, brittle nails, unsual cravings- dirt ice, poor appetite in infants and children
51
UL Fe
= 45mg to prevent GI distress chronic use of iron supplements - applies to all sources set low enough for those with genetic hemochromatosis too mcuh dietary soluble Fe can force more Fe to be absorbed (accidental poisoning in children - acute tox)
52
what is hemochromatosis
genetic problem, absorb more Fe than usual (transferrin saturated) mutation in HFE gene = low hepcidin lose ability to reduce Fe absorption liver damage, lose insulin secretion, other tissues damaged - irreversible , detect as high plasma ferritin (high stores) overr 200mcg/dL, NOT MORE Hb
53
treatment for hemochromatosis
avoid Fe( difficult bc fortification) frequent phlebotomy administer chelator to increase Fe urine losses