Folate And Cobalamin Metabolism Flashcards
Mention the water soluble vitamins
Thiamine B1 Riboflavin B2 Niacin B3 Pantothenate B5 Pyridoxine B6 Biotin B7 Folate B9 Cobalamin B12 Ascorbate C
How are water soluble vitamins absorbed❓
By Na+ coupled facilitated diffusion
Water soluble vitamins can easily be lost by cooking or storage
True or false
True
Describe the chemical structure of folate
Pteridine base \+ P-aminobenzoic acid \+ Glutamate
What is the RDA and therapeutic allowance for folate❓
RDA- 200microgram/day
Therapy- 400-800microgram/day
In what form is folate absorbed❓
In what form is folate stored in the body❓
- As THF
2. N5-methyl-THF, in the liver(about 50%), needs B12 to be active
Polyglutamyl folates must be hydrolyzed to monoglutamyl folates by ❓before absorption.
Mention a few drugs that inhibit this process
- Folate conjugase
2. Ethanol, Dilantin, Sulfasalazine
In the enterocyte, folate is ❓ and ❓
In the human portal blood, folate is ❓
Folate is reduced by ❓, synthesized by ❓
- In the enterocyte, folate is reduced and methylated
- In the human portal blood, folate is not methylated
- Folate is reduced by dihydrofolate reductase, synthesized by bacterial flora in the large intestine
Discuss the role of folate in nucleic acid metabolism
- In purine and pyrimidine synthesis-DNA and RNA synthesis
- Production of nucleotides (ATP, GTP and AMP)
- Synthesis of methyl donor s-adenosylmethionine(SAM)-used in methylation rxns i.e methylation of DNA
- THF is a coenzyme for Cl-transfer which facilitates production of “heme” in RBC and in WBC production
- Formation of brain, spinal cord and nerve cells
- In inter conversion of a.a, e.g homocysteine to methionine
Mention the effects of folate deficiency
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
List factors that predispose to folate deficiency
- Processed food/neglect of whole grains and vegetables
- Chronic diseases that increase folate requirements
- Liver disease- impairs storage
- Rapid growth periods e.g adolescence
- Pregnancy
- Heavy alcohol absorption-
impairs absorption
impairs conversation to THF
⬆️excretion - Deficiency of vitamin C and B12
- Malabsorption syndromes i.e Crohn’s disease, tropical sprue, gluten sensitive enteropathy
List a few drugs that can interfere with folic acid
- Anti-seizure meds-
•Phenobarbital, Phenytoin(Dilantin®️)
•Carbamazepine (Tegretol®️)
•Primidone(Mysoline®️) - UTI meds-Trimethoprim and sulfonamide combo (bactrim®️, septra®️)
- Diuretic for high blood pressure- Triamterene(Dyrenium®️)
- Anti-inflammatory- Sulfasalazine (azulfidine®️)
- Anticonvulsant- valproic acid(Depakene®️)
- Heartburn and reflux- Cimetidine (Tagamet®️)
- Lower cholesterol levels- cholestyramine(Locholest®️, Questran ®️)
8. Drugs that reduce folate levels: Antacids Aspirin Oral contraceptive pills Anticonvulsant Antibiotics
- Folic acid antagonists:
Methotrexate
Briefly discuss the uses of folic acid in prevention and therapy
- Prophylaxis from birth defects
- Atherosclerosis in pple with ⬆️homocysteine
- Enhanced immunity
- 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 - Psychiatric/Nervous disorders:
Dementia
Manic depression- folate+lithium
What are the dietary forms of cobalamin❓
Methylcobalamin(methyl-B12)
5-deoxyadenosylcobalamin(coenzyme-B12)
Synthetic forms include hydroxy-cobalamin and cyanocobalamin
Structure of Vitamin B12
Cobalt \+ Corrin ring \+ Chlorophyll \+ Cytochrome
How much cobalamin is stored in the body❓
Where❓
What is the RDA for adults❓
2-5mg
Liver (90%), can last for 2 years
2.4 microgram/day
Vitamin B12 can be obtained from animal diet only
True or false
True
Describe the absorption of vitamin B12
B12+IF(parietal cells of stomach) ⬇️ Ileum ⬇️ B12+TC II ⬇️ Circulation ⬇️ Bone marrow(DNA synthesis) Liver(Storage) Other tissues(DNA synthesis)
Discuss the functions of cobalamin
- Synthesis of methionine from homocysteine- coenzyme for methyltransferase
- Coenzyme for methylmalonyl CoA mutase in the conversation of methylmalonyl CoA to succinyl CoA in Krebs cycle
- Essential in RBC maturation
- 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
- Fat metabolism
- Maintains antioxidants by maintaining glutathione in the reduced form
- Myelination of neurons in the nervous system
- Cell replication
List factors that predispose to cobalamin deficiency
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
Mention the effects of B12 deficiency
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
Briefly discuss the uses of cobalamin in prevention and therapy
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
Describe the treatment plan in pernicious anemia using B12
IM injection-
100- 1000ug for 5 days
100- 1000ug for each month till corrected
List a few drugs that can interfere with cobalamin
Alcohol P-aminosalicylic acid Colchicine Neomycin Cholestrymine Anticonvulsant Metformin H2 blockers ie cimetidine Proton pump inhibitors ie omeprazole
