Seminar 2. Vit B12 deficiency and methylmalonyl acidemia

Question 1

What is anaemia?

Answer 1

where you have fewer red blood cells than normal or you have an abnormally low amount of a substance called haemoglobin in each red blood cell.

Question 2

General symptoms of anaemia

Answer 2

1. extreme tiredness (fatigue)
2. lack of energy (lethargy) 3. breathlessness
3. feeling faint
4. headaches
5. pale skin
6. noticeable heartbeats (palpitations)
7. hearing sounds coming from inside the body, rather than from an outside source (tinnitus)
8. loss of appetite and weight loss

Question 3

Symptoms of vitamin B12 deficiency

Answer 3

1. a pale yellow tinge to your skin
2. a sore and red tongue (glossitis)
3. mouth ulcers
4. pins and needles (paraesthesia)
5. changes in the way that you walk and move around
6. disturbed vision
7. irritability
8. depression
9. changes in the way you think, feel and behave
10. a decline in your mental abilities, such as memory, understanding and judgement (dementia)

Question 4

Which chemical group does Vitamin B12 (cobalamin) belong to?

Answer 4

one of a group of complex molecules with a cobalt‐containing corrin ring synthesized only by microorganisms.

Question 5

Vitamin B12 (cobalamin) is one of a group of complex molecules with a cobalt‐containing corrin ring synthesized only by _____

Answer 5

microorganisms.

Question 6

The usual dietary source of vitamin B12 for omnivores is ___

Answer 6

flesh of other animal

Question 7

An example that contains large amounts of vitamin B12

Answer 7

Faeces
-> waste matter remaining after food has been digested, discharged from the bowels; excrement.

Question 8

What is the natural source of vitamin B12 for human?

Question 9

What is the natural source of vitamin B12 for human?

Answer 9

animal‐origin food is the only natural food source of vitamin B12.

Question 10

Does plant food provide B12 source?

Answer 10

NO!

Question 11

Plant foods do not provide it unless the plant was exposed to ___

Answer 11

vitamin B12–producing bacteria

Question 12

Plant foods do not provide it unless the plant was contaminated with ___

Answer 12

vitamin B12–containing substances (soil, insect parts, etc)

Question 13

Plant foods do not provide it unless the plant was fortified with ___

Answer 13

vitamin B12 (e.g. fortified ready‐to‐eat breakfast cereals).

Question 14

Example of foods high in vitamin B12

Answer 14

dairy products, meat, liver, fish, eggs, and shellfish

Question 15

Vitamin B12 is bound to ____

Answer 15

proteins (enzymes) in food

Question 16

Vitamin B12 must be released from ____ in the stomach by the action of HCl and pepsin.

Answer 16

dietary protein

Question 17

Vitamin B12 must be released from dietary protein in the ____ by the action of HCl and pepsin.

Answer 17

stomach

Question 18

Vitamin B12 must be released from ____ in the stomach by the action of ____ (2 things)

Answer 18

HCl and pepsin (gastric enzymes)

Question 19

What are the 2 most common causes of vitamin B12 deficiency?

Answer 19

dietary deficiency and malabsorption

Question 20

What are the 2 pathways for absorption of vitamin B12?

Answer 20

1. intrinsic factor associated
2. passive diffusion.

Question 21

There are two pathways for absorption of vitaminB12, intrinsic factor associated and passive diffusion
-> Which pathway is the active process?

Answer 21

intrinsic factor associated

Question 22

Absorption of vitamin B12
-> What does the intrinsic factor associated pathway required?

Answer 22

It requires
- an intact stomach
- intrinsic factor
- pancreatic enzymes
- normally functioning terminal ileum

Question 23

There are two pathways for absorption of vitaminB12, intrinsic factor associated and passive diffusion
-> Which pathway is the active process?

Answer 23

intrinsic factor associated

Question 24

Vitamin B12 must be released from dietary protein in the stomach by the action of HCl and pepsin
-> The released free vitamin B12 then binds to ____

Answer 24

R protein

Question 25

What is R protein?

Answer 25

a haptocorrin produced by the salivary glands (free cobalamin has a very low solubility in water phase).

Question 26

The released free vitamin B12 then binds to R protein, a haptocorrin produced by the salivary glands (free cobalamin has a very low solubility in water phase). -> R protein is degraded by ____

Answer 26

pancreatic enzymes in the alkaline environment of the small intestine

Question 27

The released free vitamin B12 then binds to R protein, a haptocorrin produced by the salivary glands (free cobalamin has a very low solubility in water phase). -> R protein is degraded by pancreatic enzymes in the ____ (alkaline/acidic) environment of the small intestine

Answer 27

alkaline

Question 28

R protein is degraded by pancreatic enzymes in the alkaline environment of the small intestine -> thus releasing vitamin B12 from R protein to form ____

Answer 28

the vitamin B12–intrinsic factor complex.

Question 29

What is Intrinsic factor?

Answer 29

a 60‐kDa glycoprotein that is secreted by gastric parietal cells after stimulation by food.

Question 30

Intrinsic factor is a 60‐kDa glycoprotein that is secreted by ____ after stimulation by food

Answer 30

gastric parietal cells

Question 31

Is the vitamin B12–intrinsic factor complex stable?

Answer 31

YES

Question 32

the vitamin B12–intrinsic factor complex is stable and proceeds to ____

Answer 32

the ileum

Question 33

Once formed, the vitamin B12–intrinsic factor complex is stable and proceeds to the ileum -> What will happen to this complex?

Answer 33

The vitamin B12–intrinsic factor complex is attached to specific membrane receptors of the ileum -> then it is absorbed by endocytosis.

Question 34

Can the intrinsic factor–related process has high capacity for absorbing vitamin B12?

Answer 34

this intrinsic factor–related process has a limited capacity for absorbing vitamin B12, with a maximum of 3 μg at one meal. (large amount can be achieved by passive diffusion)

Question 35

Which Vit B12 absorption pathway is necessary for large quantities of vit B12?

Answer 35

Passive diffusion

Question 36

The rate of absorption by the passive process is less than ___ (percentage) of the ingested amount of vitamin B12.

Answer 36

1%

Question 37

Following the endocytosis of the vitamin B12–intrinsic factor complex and ______, the intrinsic factor is degraded by the lysosomal proteases and cobalamin is bound by transcobalamin‐II (TC‐II)

Answer 37

fusion of the endosomes and lysosomes

Question 38

Following the endocytosis of the vitamin B12–intrinsic factor complex and fusion of the endosomes and lysosomes, the intrinsic factor is degraded by _____

Answer 38

the lysosomal proteases

Question 39

Following the endocytosis of the vitamin B12–intrinsic factor complex and ______, the intrinsic factor is degraded by the lysosomal proteases and cobalamin is bound by transcobalamin‐II (TC‐II)

Answer 39

fusion of the endosomes and lysosomes

Question 40

Following the endocytosis of the vitamin B12–intrinsic factor complex and fusion of the endosomes and lysosomes -> the intrinsic factor is degraded by the lysosomal proteases -> cobalamin is bound by ____

Answer 40

transcobalamin‐II (TC‐II)

Question 41

What is transcobalamin‐II (TC‐II)?

Answer 41

a protein structurally related to the intrinsic factor, but produced by the intestinal epithelial cells

Question 42

Following the endocytosis of the vitamin B12–intrinsic factor complex and fusion of the endosomes and lysosomes, the intrinsic factor is degraded by the lysosomal proteases and cobalamin is bound by transcobalamin‐II (TC‐II) -> The TC‐II‐B12 complex is secreted in ____

Answer 42

the circulation

Question 43

Following the endocytosis of the vitamin B12–intrinsic factor complex and fusion of the endosomes and lysosomes, the intrinsic factor is degraded by the lysosomal proteases and cobalamin is bound by transcobalamin‐II (TC‐II) -> The TC‐II‐B12 complex is secreted in the circulation -> This complex is then taken up by ___

Answer 43

TC‐II‐receptor mediated endocytosis in the tissues

Question 44

The TC‐II‐B12 complex is secreted in the circulation and taken up by TC‐II‐receptor mediated endocytosis in the tissues -> What happen to cobalamin at this point?

Answer 44

cobalamin is converted to its methyl and adenosyl derivatives that serve as enzyme cofactors.

Question 45

ranscobalamin‐II (TC‐II), a protein structurally related to ____, but produced by the intestinal epithelial cells

Answer 45

the intrinsic factor

Question 46

Perturbation of cobalamin absorption -> What is pernicious anemia associated with gastric atrophy?

Answer 46

Pernicious anemia is the end stage of autoimmune gastritis (type A chronic atrophic gastritis or gastric atrophy) in which both the fundus and body of the stomach are involved.

Question 47

Pernicious anemia is the end stage of autoimmune gastritis (type A chronic atrophic gastritis or gastric atrophy) in which both ___ and ___ are involved

Answer 47

the fundus and body of the stomach