Iron/ B12 & Folate

Question 1

Biological functions of folate/vit B9?

Answer 1

DNA synthesis, RNA synthesis, DNA methylation, methionine and thymidylate synthesis, theres more cant bother

Question 2

What is the Folate Trap?

Answer 2

• B12 deficiency cause folate to be trapped in methyl form (methyl THF) and it can escape without being used.
• needs to be in the THF so it can be used
• DNA synthesis is affected, large RBCs with nuclear retention and flimsy membrane are formed-megaloblastic anaemia

Question 3

Plant foods contain cobalamin. True or False.

Answer 3

FALSE!!! B12 found in animal sources like beef, liver, fish, diary products.
PS. folate is mainly from plant sources

Question 4

Describe the transport & absorption of Cobalamin (B12).

Answer 4

1. Mouth: Haptocorrin/R protein in saliva binds to dietary B12 & carries it to the stomach.
2. Stomach: Gastric acid and pepsin cleaves the B12 from haptocorrin (TCI carries it to the duodenum).
3. Duodenum & jejenum: pancreatic juices and enzymes degrade the TC I and releases the cobalamin, which is now taken up by intrinsic factor.
   - IF protects the cobalamin and carries it to the cubulin in the ileum.
4. Ileum: the IF-cobalamin complex binds to cubulin and is taken up into the enterocyte (by Ca2+ dependent passive transport)
5. Enterocyte: the IF-cobalamin complex is engulfed by lysosomes, where enzymes degrade the IF and release the cobalamin into the cytoplasm where it is taken up by TCII.
   - TC II/Cobalamin complex exit the enterocyte into systemic circulation- to the bone marrow & tissues.

Question 5

B12 is never left unattended. True or False

Answer 5

True- it is always bound to something.

Question 6

Describe TCI?

Answer 6

• Binds 70% of cobalamin, protects cobalamin from the acid environment of the GI tract, n neutralizes the function of cobalamin- cobalamin appears functionally dead.
• Largely synthesized by granulocytes and macrophages.
• Aka haptocorrin and R protein

Question 7

Describe TCII?

Answer 7

• Binds 30% of circulating cobalamin, and transports cobalamin to target cells where they are used, like in bone marrow.
• Congenital TC deficiency causes megaloblastic anaemia because of failure of B12 to enter marrow

Question 8

What is megaloblastic anaemia?

Answer 8

• Caused by a deficiency (or defective metabolism) of B12 and folate which in turn causes impaired DNA synthesis-ineffective erythropoiesis.
• Results in abnormal RBCS; features- anaemia, macrocytosis, hypersegmented neutrophils, red cell fragments, raised LDH and thrombocytopenia.

Question 9

The dietary forms of B12 and folate are the same as that in the circulation. True or false.

Answer 9

False-the form in circulation is different

Question 10

Normal dietary intake of B12 and folate?

Answer 10

7-30 micrograms and 200-250 micrograms resp.

Question 11

Cooking has a little effect on folate. T or F.

Answer 11

F- folate is easily destroyed by over-cooking

Question 12

Body stores of B12 and folate?

Answer 12

2-3 mg and 10-12 mg resp.

Question 13

Absorption site for B12 and folate

Answer 13

Ileum and duodenum/jejunum resp.

Question 14

In order to be absorbed folate is converted to what?

Answer 14

methyltetrahydrofolate- reduced monoglutamate form which circulates the plasma.

Question 15

Severe deficiency of B12 is usually caused by what?

Answer 15

pernicious anaemia
note: less commonly in veganism

Question 16

What is pernicious anaemia?

Answer 16

• an autoimmune attack on the gastric mucosa leading to atrophy of the stomach and the secretion of intrinsic factor (IF) is absent.
• Therefore, there is malabsorption of B12 due to lack of IF.

Question 17

Why do pregnant women require an increased need for folate?

Answer 17

Due to excess cell turnover, because folate is degraded due to an increase in DNA synthesis (thymidylate synthesis).

Question 18

How does a folate deficiency cause megaloblastic anaemia?

Answer 18

Folate deficiency inhibits thymidylate synthesis which is the rate limiting step of DNA synthesis.

Question 19

How does B12 deficiency cause megaloblastic anaemia?

Answer 19

B12 deficiency indirectly reduces the amount of folate coenzyme which is necessary for thymidylate synthesis. In turn, affects DNA synthesis.

Question 20

Iron deficiency is the main cause of what kinda anaemia?

Answer 20

• Microcytic, hypochromic anaemia (red cells are small and pale)
• low MCV and MCH
  note: iron deficiency is the main cause of anaemia.

Question 21

which enzyme other than hephaestin catalyses oxidation of iron to the ferric form?

Answer 21

caeruloplasmin (copper-containing enzyme)

Question 22

iron is mobilised after what?

Answer 22

reduction to the ferrous form (Fe2+)

Question 23

transport and storage of iron is largely mediated by which proteins?

Answer 23

• transferrin
• transferrin receptor 1
• ferritin

Question 24

What does hepcidin do?

Answer 24

• It’s a hormone produced by the liver that inhibits the release of iron from macrophages and from enterocytes (by closing the ferroportin) into the plasma.
• If increased, it reduces iron absorption

Question 25

Too much iron leads to an increase in hepcidin, and iron deficiency leads to a decrease in hepcidin. T or F.

Answer 25

T- amt of iron is directly proportional to the amt of hepcidin

Question 26

Why does ineffective erythropoiesis, increase iron absorption?

Answer 26

Because erythroblasts secrete 2 proteins that suppress the hepcidin synthesis, and a decrease in hepcidin allow for an increase in iron absorption. note: hypoxia also suppresses hepcidin synthesis

Question 27

Inflammation, IL-6 and other cytokines increase hepcidin synthesis. T or F.

Answer 27

T- reduces iron absorption

Question 28

Most dietary iron is absorbed. T or F.

Answer 28

F- most dietary iron remains unabsorbed - 5-10 % is absorbed normally - 20-30 % is absorbed in iron deficiency and pregnant women (bcuz 35% of 300 mg of iron is transferred to the fetus)

Question 29

major causes of iron deficiency?

Answer 29

- chronic blood loss (uterine, gastrointestinal) - increased demands (pregnancy, growth) - malabsorption - poor diet (rarely the sole cause of iron deficiency)

Question 30

In iron deficiency, the iron stores are completely depleted. T or F.

Answer 30

T- takes a while before it reaches anaemia cuz the iron stores will be used up

Question 31

what is hemochromatosis?

Answer 31

- disorder in iron metabolism where there is excess iron absorption, saturation of iron-binding proteins and deposition of hemosiderin in the tissues. - excess iron deposition leads to liver cirrhosis bronze diabetes (bronze skin + diabetes).

Question 32

iron is absorbed mainly where?

Answer 32

the duodenum note: in the ferrous state

Question 33

iron varies directly with what?

Answer 33

rate of erythropoiesis

Question 34

what factors favour iron absorption? hint: 8

Answer 34

- ferrous form - inorganic iron - acids- HCl, vit C - solubizing agents- sugar, amino acids - iron deficiency - ineffective erythropoiesis - pregnancy - primary haemochromatosis *decreasing hepcidin

Question 35

what factors reduce iron absorption? hint:9

Answer 35

- ferric form - organic iron - alkalis- antacids - precipitating agents-phosphates - iron excess - decreased erythropoiesis - infection/ inflammation - tea - desferrioxamine *increasing hepcidin

Question 36

describe the process of iron transport/absorption?

Answer 36

- first, dietary iron is reduced from the ferric state (Fe3+) to the ferrous state (Fe2+) by DCYTB. - Fe2+ can now enter the enterocyte but its transferred in by DMT1 - in the enterocyte, Fe2+ can either be stored as mucosal ferritin then shed as stool or it can be transported through ferroportin into circulation - Fe2+ outside of the enterocyte is oxidized back to the Fe3+ by hephaestin - Fe3+ now in the blood vessel is bound to transferrin which carries it either to the bone marrow for erythropoiesis or to the liver to stimulate hepcidin

Question 37

what does low plasma iron concentrations (hypoferremia) cause?

Answer 37

anaemia (cuz of decreased Hb synthesis)

Question 38

Iron is transported in the ferric form (Fe3+) by transferrin and absorbed in the ferrous form (Fe2+) by DMT-1. T or F.

Answer 38

T

Question 39

the majority of storage iron is present as ferritin, and haemosiderin is predominantly found in macrophages rather than hepatocytes. T or F.

Answer 39

T

Question 40

TC deficiency causes metaloblastic anaemia because of failure of B12 to enter marrow (and other cells) from plasma but the serum B12 level in TC deficiency is normal. T or F.

Answer 40

T

Question 41

Folate deficiency is thought to cause megaloblastic anaemia by inhibiting the thymidylate synthesis, a rate-limiting step in DNA synthesis. T or F.

Answer 41

T note: Lack of B12 prevents the demethylation of methyl THF, thus depriving cells of THF and so of folate polyglutamate coenzyme- which is needed for thymidylate synthesis

Question 42

clinical features of megaloblastic anaemia?

Answer 42

- mild jaundice- excess breakdown of haemoglobin resulting from increased ineffective erythropoiesis in the bone marrow - Glossitis, angular stomatitis and mild symptoms of malabsorption with loss of weight