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Haematology > Folate And Cobalamin Metabolism > Flashcards

Folate And Cobalamin Metabolism Flashcards

1
Q

Mention the water soluble vitamins

A 
Thiamine B1
Riboflavin B2
Niacin B3
Pantothenate B5
Pyridoxine B6
Biotin B7
Folate B9
Cobalamin B12
Ascorbate C
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2
Q

How are water soluble vitamins absorbed❓

A

By Na+ coupled facilitated diffusion

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3
Q

Water soluble vitamins can easily be lost by cooking or storage

True or false

A

True

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4
Q

Describe the chemical structure of folate

A 
Pteridine base
\+
P-aminobenzoic acid
\+
Glutamate
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5
Q

What is the RDA and therapeutic allowance for folate❓

A

RDA- 200microgram/day

Therapy- 400-800microgram/day

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6
Q

In what form is folate absorbed❓

In what form is folate stored in the body❓

A
  1. As THF

2. N5-methyl-THF, in the liver(about 50%), needs B12 to be active

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7
Q

Polyglutamyl folates must be hydrolyzed to monoglutamyl folates by ❓before absorption.

Mention a few drugs that inhibit this process

A
  1. Folate conjugase

2. Ethanol, Dilantin, Sulfasalazine

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8
Q

In the enterocyte, folate is ❓ and ❓

In the human portal blood, folate is ❓

Folate is reduced by ❓, synthesized by ❓

A
  1. In the enterocyte, folate is reduced and methylated
  2. In the human portal blood, folate is not methylated
  3. Folate is reduced by dihydrofolate reductase, synthesized by bacterial flora in the large intestine
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9
Q

Discuss the role of folate in nucleic acid metabolism

A
  1. In purine and pyrimidine synthesis-DNA and RNA synthesis
  2. Production of nucleotides (ATP, GTP and AMP)
  3. Synthesis of methyl donor s-adenosylmethionine(SAM)-used in methylation rxns i.e methylation of DNA
  4. THF is a coenzyme for Cl-transfer which facilitates production of “heme” in RBC and in WBC production
  5. Formation of brain, spinal cord and nerve cells
  6. In inter conversion of a.a, e.g homocysteine to methionine
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10
Q

Mention the effects of folate deficiency

A 
Impaired DNA synthesis
⬇️
Arrest of cell cycle of rapidly proliferative cells(RBC)
⬇️
Megaloblastic anemia
⬇️
Fatigue, weakness, shortness of breath

Impaired cell growth in GI, inflammation of tissues in the mouth, stomach etc

Impairment of WBC development 
⬇️
Leukopenia 
⬇️
Reduced immune response

Impaired fetal growth and development
⬇️
Birth defects e.g spina bifida

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11
Q

List factors that predispose to folate deficiency

A
  1. Processed food/neglect of whole grains and vegetables
  2. Chronic diseases that increase folate requirements
  3. Liver disease- impairs storage
  4. Rapid growth periods e.g adolescence
  5. Pregnancy
  6. Heavy alcohol absorption-
    impairs absorption
    impairs conversation to THF
    ⬆️excretion
  7. Deficiency of vitamin C and B12
  8. Malabsorption syndromes i.e Crohn’s disease, tropical sprue, gluten sensitive enteropathy
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12
Q

List a few drugs that can interfere with folic acid

A
  1. Anti-seizure meds-
    •Phenobarbital, Phenytoin(Dilantin®️)
    •Carbamazepine (Tegretol®️)
    •Primidone(Mysoline®️)
  2. UTI meds-Trimethoprim and sulfonamide combo (bactrim®️, septra®️)
  3. Diuretic for high blood pressure- Triamterene(Dyrenium®️)
  4. Anti-inflammatory- Sulfasalazine (azulfidine®️)
  5. Anticonvulsant- valproic acid(Depakene®️)
  6. Heartburn and reflux- Cimetidine (Tagamet®️)
  7. Lower cholesterol levels- cholestyramine(Locholest®️, Questran ®️)
8. Drugs that reduce folate levels:
Antacids
Aspirin
Oral contraceptive pills
Anticonvulsant 
Antibiotics
  1. Folic acid antagonists:
    Methotrexate
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13
Q

Briefly discuss the uses of folic acid in prevention and therapy

A
  1. Prophylaxis from birth defects
  2. Atherosclerosis in pple with ⬆️homocysteine
  3. Enhanced immunity
  4. Cancer:
    ⬇️risk of colon cancer in pple with inflammatory bowel disease
    ⏺Folate+Vitamin A can reduce the risk of cervical dysplasia
    ⏺Folate+Vitamin B12 can reduce dysplasia in the lungs of smokers
    ⏺THF+Vitamin B12 detoxify homocysteine to methionine
    ⬇️risk of lung cancer
  5. Psychiatric/Nervous disorders:
    Dementia
    Manic depression- folate+lithium
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14
Q

What are the dietary forms of cobalamin❓

A

Methylcobalamin(methyl-B12)

5-deoxyadenosylcobalamin(coenzyme-B12)

Synthetic forms include hydroxy-cobalamin and cyanocobalamin

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15
Q

Structure of Vitamin B12

A 
Cobalt
\+
Corrin ring 
\+
Chlorophyll 
\+
Cytochrome
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16
Q

How much cobalamin is stored in the body❓

Where❓

What is the RDA for adults❓

A

2-5mg

Liver (90%), can last for 2 years

2.4 microgram/day

17
Q

Vitamin B12 can be obtained from animal diet only

True or false

A

True

18
Q

Describe the absorption of vitamin B12

A 
B12+IF(parietal cells of stomach)
⬇️
Ileum
⬇️
B12+TC II
⬇️
Circulation 
⬇️
Bone marrow(DNA synthesis)
Liver(Storage)
Other tissues(DNA synthesis)
19
Q

Discuss the functions of cobalamin

A
  1. Synthesis of methionine from homocysteine- coenzyme for methyltransferase
  2. Coenzyme for methylmalonyl CoA mutase in the conversation of methylmalonyl CoA to succinyl CoA in Krebs cycle
  3. Essential in RBC maturation
  4. Folate metabolism- activation of folate
5. The SAM cycle also requires B12:
•methylation of PE(phosphatidylethanolamine) to PC(phosphatidylcholine) for myelination 
•norepinephrine➡️epinephrine 
•acetylserotonin➡️melatonin 
•DNA methylation 
•Guanidinoacetate➡️creatine
•methylation of drugs eg mercaptopurine
  1. Fat metabolism
  2. Maintains antioxidants by maintaining glutathione in the reduced form
  3. Myelination of neurons in the nervous system
  4. Cell replication
20
Q

List factors that predispose to cobalamin deficiency

A

Old age: ⬇️gastric secretion and IF

Liver disease: impaired storage

Strict vegetarianism: no animal products

Cigarette smoking

Chronic gastritis: atrophy of parietal cells

Intestinal diseases:
•chronic enteritis with diarrhea: ⬇️absorption
•Tapeworm infection
•Pancreatic insufficiency: failure to digest haptocorrin
•Inflammatory vowel disease
•Receptor deficiencies

21
Q

Mention the effects of B12 deficiency

A

Pernicious anemia

Neurological changes:
Numbness and tingling in extremes due to diminished myelination

Difficultly in maintaining balance, depression, confusion, dementia, poor memory

Reduced platelet function

Impaired WBC development

Impaired cell replication

22
Q

Briefly discuss the uses of cobalamin in prevention and therapy

A

Pernicious anemia

Megaloblastic anemia w folate

Psychiatric/nervous disorders ie dementia and memory loss

Prevention of atherosclerosis

Prevention of dysplasia in smokers

Reduction in peripheral nerve disorders in diabetes etc

5-10g IV of hydroxyB12 can be used in cyanide poisoning to form cyanocobalamin

23
Q

Describe the treatment plan in pernicious anemia using B12

A

IM injection-

100- 1000ug for 5 days
100- 1000ug for each month till corrected

24
Q

List a few drugs that can interfere with cobalamin

A 
Alcohol
P-aminosalicylic acid 
Colchicine 
Neomycin 
Cholestrymine 
Anticonvulsant 
Metformin 
H2 blockers ie cimetidine 
Proton pump inhibitors ie omeprazole

Haematology (5 decks)

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