Vit B12 & Folate Metabolism Flashcards
cobalamin
vit B 12
T or F. Vit B 12 is an essential nutrient and the body is unable to make so it must be obtained from dietary sources
T!
Role of Vitamine B12
- DNA synthesis: tissue growth and regeneration
- maintenance of myelin sheath (B12 only)
- functions as a coenzyme: metabolism of homocysteine; methylmalonyl CoA metabolism
hydroxocobalamin
mechanism involves rapidly removing cyanide (fires) from tissue by forming cyanocobalamin, which is then excreted unchanged in the urine
dietary sources of B12
- eggs
- red meat and poultry
- milk and milk products
- some fortified cereals and meat substitutes
Proteins involved in Vit B12 absorption and metabolism
- Haptocorrin (R protein or Transcobalamin I)
- Intrinsic factor
- Transcobalamin (II)
Haptocorrin
- present in saliva
- delivers vit B12 to the duodenum
Intrinsic Factor
- released from gastric parietal cells
- picks up vit B12 from duodenum for transport across the ileum
Transcobalamin II
- from enterocytes
- main transporter of vit B12 to tissues
causes of vitamin B12 deficiency
- inadequate intake (rare)
- increased need (pregnancy, lactation, and growth)
- impaired absorption
> failure to separate from food proteins or haptocorrin
> lack of IF
> malabsorption
> competition for vit B12
What causes failed separation of B12
- hypochloridia in the stomach: increased pH results in inability to release B12
- vit B12 remains complexed with food or with haptocorrin
Causes of lack of IF
- gastrectomy: loss of parietal cells
- H. pylori infection: colonizes gastric mucosa and progressively destroys parietal cells
- hereditary IF deficiency: absence of non-functionality of IF
- autoimmune disease: pernicious anemia
which cells produce IF?
parietal cells
autoimmune disorder characterized by impaired absorption of vit B12 due to the lack of IF
Pernicious Anemia
Progression of Pernicious Anemia
- autoimmune destruction of parietal cells => decreased IF
=> chronic inflammation and gradual atrophic gastritis
=> decreased If and achlorhydria
=> detectable levels of Abs to intrinsic factor or parietal cells
Malabsorption of B12
- tropical sprue
- Celiac disease
- surgery
- inflammatory bowel disease
- hereditary disorders
> RARE; autosomal recessive mutations resulting in decreased endocytosis of IF-B12 complex or decreased transcobalamin
Diphyllobothrium latum
- fish tapeworm
- competes for B12 with IF
overgrowth of bacteria that utilize vit B12 in stenotic loops of the intestine
Blind loop syndrome
folic acid vs. folate
- folate = general term for all forms
- folic acid = synthetic form found in supplements
What is Folate used for?
- DNA synthesis
- many metabolic functions: homocysteine metabolism, not for methylmalonic acid metabolism; metabolism of some amino acids and nucleotides
- neurological development of fetus
dietary sources of folate
- leafy green vegetables
- legumes
- liver and red meat
- fortified cereals
- oranges and some fruits
- yeast
cooking folate vs vit B12
Cooking folate can inactivate it, whereas B12 cooked is still gonna be there (eggs, meat, etc.)
T or F. Folate is heat-stable
F! it is heat-labile
Which has a higher rate of loss - Folate or Vitamin B12?
Folate! stores can be depleted in months!
Process of Folate absorption and metabolism
- absorbed in jejunum in the polyglutamic acid form (no binding protein needed)
- hydrolyzed to monoglutamate, then reduced and methylated to methyl tetrahydrofolate (5-methyl THF)
- transported to liver and tissues by proteins
Causes of Folate deficiency
- inadequate intake: poor diet, overcooked foods, alcoholism
- increased need
- impaired absorption
- impaired use: drug-induced
- excessive loss through hemodialysis
T or F. Both Vitamin B12 and Folate are involved in the synthesis of methionine from homocysteine
- Folate is the methyl group donor
- vit B12 is the coenzyme for methyltransferase
- further rxns take place which result in DNA synthesis
T or F. Need folate in production of heme, not B12
F! need B12 for heme production
Treatment for Vit B12 and folate deficiencies
- correct deficiency (iron concurrently given); quick recovery!
- treat CAUSE of deficiency
Lab tests for Vit B12 deficiency
- serum gastrin and gastric analysis
- antibody assays: IF and parietal cells
- stool analysis for parasites
Symptoms of B12 and Folate deficiencies
- anemia
- GI symptoms
- Glossitis
- neurological symptoms (B12 ONLY)
Results of B12 and Folate deficiencies
- decreased THF => decreased dTTP so uridine is incorporated into DNA instead which leads them to break = non-functional DNA
- increased homocysteine: hyperhomocysteinemia may be associated w atherosclerosis and blood clots
Screening tests for vit B12 and folate deficiencies
- CBC = decreased Hgb, pancytopenia w reticulocytopenia, high MCV, increased RDW
- peripheral blood smear: macroovalocytes, hypersegmented neutrophils, tears, schistocytes, HJ bodies, basophilic stippling
Confirmatory Testing for Folate and B12 defs
- serum vit B12 and Folate (immunoassay)
- bone marrow examination: megaloblastic changes, nuclear-cytoplasmic asynchrony, decreased M:E ratio
- methylmalonic acid levels
- homocysteine levels
