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House Hemat > Cobalamin And Folate > Flashcards

Cobalamin And Folate Flashcards

1
Q

folate and vitamin B12

_____-soluble vitamins important in the formation of ______ cells, the _____ system, and _____

A

Water

red blood

nervous

DNA

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2
Q

Folic acid and vitamin B12

Required for _____ synthesis and ______ maturation

Two vitamins combine in ______ reaction

______ group is transferred to _____ to make ______

Premature _____ Disease

Peripheral _______ Disease

A

DNA; red cell

methionine synthase

Methyl; homocysteine; methionine

Coronary Artery

Vascular

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3
Q

Decrease in either cobalamin or folate leads to ___ease in homocysteine level

A

Incr

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4
Q

Deficiency of cobalamin and not folate, leads to change in RBC shape

T/F

A

F

It’s both

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5
Q

Megaloblastic erythropoiesis is when there is defect in ________ and the cells are arrested at the ____ phase

A

DNA synthesis; G2

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6
Q

Effects of folate deficiency

Main manifestations

______, symptoms of _____, and ____ problems

A

glossitis

anemia

GI

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7
Q

Effects of folate deficiency

Lab work

____ease in MCV– (smaller or larger?) than ____

A

Incr

Larger

96 fL

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8
Q

Best test for folate levels is the _________ level

this is the level in _____ and is not affected by ______

A

red blood cell

tissues

recent intake

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9
Q

Recommended intake of folate for adults is ____ micrograms per day, and for women of childbearing age is ____ micrograms per day

A

400

600

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10
Q

Effects on the Body—vitamin B12 deficiency

Main manifestations
same as those for folate but may be a more serious presentation with peripheral _________, degeneration of the _____, or ___ of ____ matter of brain

A

peripheral neuropathy

spinal cord

demyelination; white

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11
Q

Effects on the Body—vitamin B12 deficiency

Patient may present with difficulty ____, _____ , loss of _____ function, and a positive _____ test

A

walking

parasthesia

memory; Romberg

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12
Q

Recommended intake of vitamin B12 for adults is ____ micrograms per day, and for women of childbearing age is ___ micrograms per day

A

2.4

2.6

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13
Q

The word folic acid is derived from the latin word _____ which means ____.

A

folium

Leave

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14
Q

Folic acid consist of 3 component:

______
________
________ residue (___ residue)

Hence it is known as ________

A

Pteridine ring

PABA ( P amino benzoic acid)

Glutamic acid; 1-7

Pteroyl-glutamic acid

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15
Q

Absorption of folate

Poly glutamate, The ______ side chain are cleaved by the enyzme _______ or ___________

A

glutamate

folate conjugase

polypolyglutamase hydrolase.

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16
Q

Most of the dietary forms of folate exist as _________

A

polyglutamate

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17
Q

Absorption of folate

Poly glutamate can be absorbed in the intestine.

T/F

A

F

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18
Q

Absorption of folate

Only the _______ form is absorbed from the intestine

A

monoglutamyl

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19
Q

The enzyme folate conjugase is present in the ____________

A

duodenum and jejunum

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20
Q

Absorption of folate

Mucosal uptake and metabolism in the mucosal cell
In the mucosal cell folate _______ is reduced to ______ and ____ to form __________ in circulation

A

monoglutamate

tetrahydrofolate

methylated

N 5 methyl tetrahdrofolate

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21
Q

Storage of folate

Inside the cell, tetrahydrofolate are found as ______ with ___ amino acid residue

A

polyglutamate

5-6

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22
Q

______ version of folate is most potent

A

Polyglutamate

5-6 residue

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23
Q

_______ is the storage form of folic acid.

A

Polyglutamate

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24
Q

Folate mainly stored in the ____ (10-20mg)

A

liver

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25
Q

Folic acid is biologically active

T/F

A

F

It is not

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26
Q

The active coenzyme forms of folic acid are:
_____________ (____)
______________
______________ (______)
_________________ (_______)

A

N5 methyl tetrahydrofolate ;N5FH

N5 N10 methylene tetrahydrofolate

N10 formyl tetrahydrofolate ; N10 formyl FH4

N5 formimino tetrahydrofolate; N5 formimino FH4

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27
Q

The coenzyme of folic acid are actively invovled in the ____ metabolism.

A

one carbon

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28
Q

THF acts as an acceptor or donor of one carbon unit (_____,_____,______,______etc)in reaction involving _______ and ——- metabolism.

A

formyl,methyl , methylene, methynyl

amino acids and nuclotide

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29
Q

The one carbon units bind with THF at position __________________________ of pteroyl structure

A

N5 or N10 or on both N5 & N10

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30
Q

All of the biological functions of folic acid are performed by ___ and its _____ derivatives.

Hence folic acid must first be reduced to ______.

A

THF

methylated

THF

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31
Q

Reduction of folic acid to THF

This —— electron reduction proceeds in two chemical steps both catalyzed by the same enzyme,_________

Folic acid is first reduced to ______ and then to ________.

Each step consumes ___ molecule of ____ (biosynthetically derived from ______) and produces one molecule of _____.

A

four; dihydrofolate reductase

dihydrofolate; tetrahydrofolate

one; NADPH; vitamin B3

NADP

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32
Q

Reduction of folic acid to THF

Mechanistically, _____ is transferred from NADPH to the ____ position of the ________

A

hydride; C6

pteridine ring

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33
Q

One carbon atom reaction

A one-carbon (1C) methyl group is added to tetrahydrofolate through the action of ________________ to yield ____________

This reaction also consumes _______ and _______ and produces ______ and _____

A

serine hydroxymethyltransferase (SHMT)

5,10-methylenetetrahydrofolate(5,10-CH2-THF).

serine and pyridoxal phosphate

glycine and pyridoxal.

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34
Q

One carbon atom reaction

A second enzyme, ___________ oxidizes ________ to an iminium cation which in turn is ______ to produce _______ and _______

A

methylenetetrahydrofolate dehydrogenase (MTHFD2)

5,10-methylenetetrahydrofolate

hydrolyzed

5-formyl-THF and 10-formyl-THF

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35
Q

Synthesis of Deoxythymidylate (dTMP)

________________ transfers a methyl group to ________ to form ______

A

N5,N10-methylene tetrahydrofolate

deoxyyuridylate (dUMP)

dTMP

36
Q

dTMP is Essential for DNA synthesis.

T/F

A

T

37
Q

N5,N10-methylene tetrahydrofolate is absolutely essential for __________

This is important in rapidly dividing cell eg ______,_______,_______,________ cells .

A

DNA synthesis.

RBC , hair follicles, intestinal mucosa cells and cancer

38
Q

_________ (analogue of folic acid)

A

Methotrexate

39
Q

Which binds better to folate reductase ?

Methotrexate or folate?

A

Methotrexate binds to folate reductase 1000 times more tightly than folate.

40
Q

Methotrexate inhibits the conversion of ________ and _______ into active tetrahydrofolate

A

folate and dihydrofolate

41
Q

Rich sources of folate are _____________ such as spinach, cauliflower

Poor sources of folate are ____,____,_____,____

A

green leafy vegetables

liver, kidney ,milk ,fruits

42
Q

Folic acid deficiency

Dietary deficiency

This include:
Inadequate intake seen in _______
________ of food resulting in loss of folic acid activity
Impaired absorption due to __________
Drug interfere with folic absorption – _______
Increase demand in _______

A

alcholics

Overcooking

small intestinal disease

pregnancy

43
Q

_________ is the most common cause of folic acid deficiency

A

Dietary deficiency

44
Q

Causes of folic acid deficiency

________ anaemia
Loss of folic acid seen in patient undergoing ______
Impaired synthesis of active form seen in patients receiving _______ such as ______

A

Haemolytic

dialysis

folic acid antagonist

methrotrexate

45
Q

Clinical features of folic acid deficiency

______ anaemia charaterised by ___chromic ___cytic anaemia ( due to ________)

Megaloblastic changes are seen in marrow & mucosa

Patient look ____

_________

A

Megaloblastic; hyper; macro

maturation block

pale

Glossitis

46
Q

Laboratory findings in folate deficiency

Peripheral smear: ___cytic ___chromic anaemia

Hyper____ _______

A

macro; hyper

segmented

neutrophils

47
Q

In pregnancy folic acid helps prevent _____

Mainly involve the ______ and _____

deficiency result in impaired and aberrant neural development.

A

neural tube defects

brain and spinal cord,

48
Q

Homocyteinaemia is a risk factor for ____

A

CHD

49
Q

Folic acid is required for the conversion of homocyteine to ______

A

methionine

50
Q

Homocysteine level is also increased in vit.______ and _____ deficiency

A

B12

pyridoxine

51
Q

Cobalamin is an analogous to ____ in its ______ having as its base a ______ ring.

A

heme

structure

tetrapyrole

52
Q

Instead of iron as a metal co factor for heme, cobalamin has _____ in a coordination state of _____ with;
A ________ group nitrogen coordinated to a one axial position.
The 4 equatorial positions coordinated by the ________ of ________ group and

A

cobalt; six

benzimidazole

nitrogens of 4 pyrrrole

53
Q

Cobalamin (vitamin B12) exit in a number of different chemicaal forms.
All have a _____ atom at the centre of a _____ ring.

A

colbalt; corrin

54
Q

Forms of cobalamin

In nature it is mainly in the ________, form which is located in the _________

The other major natural cobalamin is _________, the form in _______ and ______

There are also minor amount of __________ to which methyl and adenosyl are rapidly converted to by exposure to ____

A

2-deoxyadenosyl (ado)

mitochondria

methylcobalamin; human plasma and cell cytoplasm.

hydroxocobalamin;

Light

55
Q

Cobalamin is synthesized solely by _______.

A

microorganism

56
Q

Strict ________ are at risk of developing B12 deficiency

A

vegetarians

57
Q

Ruminants obtain cobalamin from the ______, but the only source for human is _______ of _____ origin

Fish
Meat
Dairy product

A

foregut

food of animal origin.

58
Q

Absorption of cobalamin

Two mechanism exist:
Passive absorption- occuring through _____,_____,_____ mucosa; it is (slow or rapid?) but extremely inefficient,<___% of an oral dose being absorbed by this process

A

buccal, duodenal and ileal

Rapid ; 1

59
Q

Absorption of cobalamin

Two mechanism exist:
_________
__________

A

Passive absorption
Active absorption

60
Q

Absorption of cobalamin

Two mechanism exist:

Active absorption- normal physiologic mechanism is active; it occurs through the _____ and is efficient for small(a few microganism)oral doses of cobalamin and is mediated by ________

A

iluem

gastric intrinsic factor (IF)

61
Q

Absorption of cobalamine

Dietary cobalamin is released from protein complexes by enzymes in the ____,_____,_ and _____
It combines (slowly or rapidly?) with _______ that belongs to the family of cobalamin-binding protein known as _________ which are digested by ______ and the cobalamin transferred to intrinsic factor (IF)

A

stomach, duodenum and jejunum.

Rapidly ; salivary glycoprotein

pancreatic trypsin

62
Q

Role of intrinsic factor

Intrinsic factor is produced in the ____ cells of the ______ and ______ of the stomach, and its secretion parellels that of _________

A

parietal

fundus and body

63
Q

The intrinsic factor -cobalamin complex passes to the the _____, where IF attaches to a specific receptor ( ____) on the microvillus membrane of the enterocytes.

A

iluem

cubulin

64
Q

Cubulin with its ligand IF-cobalamin complex is ________.
The complex enters the _____ cell where _______

A

endocytosed

ileal

IF is destroyed.

65
Q

In the absence of IF, inadequate amount of cobalamin are absorbed resulting in _________ anaemia.

A

megaloblastic

66
Q

the dietary requirement is appx. ____ng/day)

A

200

67
Q

When the root cause of the resultant megaloblastic anaemia is absence of or inadequate amount of IF the condition is called _________ anaemia.

A

pernicious

68
Q

Transportation of cobalamin

Three plasma transport protein have been identified:
________
_______/________
______

A

Intrinsic factor
Transcobalamin I; haptocorrin
Transcobalamin II

69
Q

Transcobalamin is secreted by _______

A

white cell.

70
Q

Although approx. —% of plasma vit.B12 in circulation binds to the transport proteins only ___________ is capable of transporting vitamin B12 into cells.

A

90

transcobalamin II

71
Q

The body usually has sufficient stores of vitamin b12

T/F

A

T

72
Q

So Vit.B12 deficiency develops more than ______ after absoption ceases.

A

3 years

73
Q

Cobalamin plays a vital role in the catabolism of ________, threonine, ______ and the ______ amino acids (leucine,isoleucineand valine.

The degradation of these compounds produces the same metabolite ________

A

odd-chain fatty acids

methionine

branchede chain

Propionyl CoA.

74
Q

Cobalamin in In DNA synthesis

It’s the biochemical basis for the development of ________ specifically the _______ synthesis reaction which converts ______-_____

A

megaloblatics anaemia

thymidylate

dUMP - dTMP

75
Q

Cobalamin In Methionine metabolism

Its required for the conversion of ___________ into ______

Cobalamin must undergo _______ first tho to _______ and it recieves the group from ______________ thus regenerating ————- that participate in the other one carbon transfer in ____metabolism or ______ remodeling.

A

homocysteine into methionine.

Methyl transfer
methyl cobalamin.

N5 –methyl tetrahydrofolate

tetrahydrofolatet

purine ; pyrimidine

76
Q

Vit B12 is important in conversion of ______ to _______ in Krebs cycle.

In this reaction B12 acts as co-enzyme for _____________

A

methylmalonyl CoA

succinyl CoA

methylmalonyl Co A mutase.

77
Q

Vitamin B12 is Necessary in the synthesis of _____ from homocysteine.

In this reaction ________ are involved.

B12 acts as a co-enzyme (______) for ________.

A

methionine

both vit B12 and folic acid

methyl cobalamin

methyltransferase

78
Q

Causes of vitamin B12 deficiency

_____ deficiency (rare)
_______ anaemia( most common case of Vit.B12 )
______tomy
_______ insufficiency
__________ (rare)
___________ infection.

A

Dietary; Pernicious

Gastrec

Pancreatic

Fish tape worm

Helicobacter pylori

79
Q

Causes of vitamin B12 deficiency

_______ disease
Surgical resection
Decrease _____ absorption of vit.B12
_________ deficiency (rare)
_______ syndrome

A

Crohn’s

ileal

Transcobalamine II

Blind loop

80
Q

FOLATE TRAP

In cobalamin deficiency, the methionine synthase reaction cannot occur, __________ accumulate and the other C-1 donor forms of tetrahydrofolate cannot be formed.

The methionine synthesis from homocysteine ceases , allowing the “trapping” of the folate pool as ______, thereby diminishing level of _______________ which is required for the methylation of ____ to ____ , thus in its deficiency, the ________ reaction is slow and _____ levels drops and hence _____ synthesis is also slowed down due to non availability of ______.

A

N5-methyltetrahdrofolate

N5 methyltetrahdrofolate

N5,N10 methylenetetrahdrofolate.

dUMP to dTMP
thymdilate synthase ; dTMP

DNA; deoxyribonucluotide

81
Q

MEGALOBLASTIC ANAEMIA

The Hall mark of symptomatic vitamin B12 deficiency is ______________

In advance cases the anaemia may be severe with haematocrit as low as ___% an may be accompanied with _____ and ______

The megaloblastic state also produces changes in mucosal cells, leading to _____, as well as other vague ______ disturbances such as _____ and diarrhea.
Patients are usually ____ and may be midly _____.

A

megaloblastic anaemia.

10-15

lecopenia and thrombocytopenia.

glossitis; gastrointestinal; anorexia

pale; icteric

82
Q

Biochemical findings in folic acid deficiency

Low plasma folic acid level < ___ng/ml

Low red cell folic acid level < ____ng/ml

_______ pLasma vit.B12

_____ease plasma LDH

A

3

150

Normal

Incr

83
Q

Folic acid excretion test:

Folic acid deficiency is associated with increase excretion of _________ in urine. Due to impaired converssion of ____ to _____ in a reaction requiring ______

A

formiminoglutamate ( FIGLU)

FIGLU; glutamate

FH4

84
Q

Vitamin B-12

Normal diet contains btw 5-30 ug of cobalamin daily
Adult daily losses mainly in urine and feaces are between __-___ug (~0.1% of body stores) as the body does not have the ability to degrade cobalamin.
Daily reqiurement is about ___-____ug.

Body stores of __-___ mg, sufficient for__-___ years if supplies are not cut off

A

1-3

1-3

2-3

3-4

85
Q

Cobalamin binds to _____ (aka ____, _____) to protect it from acid in the stomach.

This is destroyed in the intestine by _____ so that cobalamin can bind to ______

A

R protein(Transcobalamin 1, haptocorrins)

Pancreatic trypsin

Intrinsic factor

House Hemat (29 decks)

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