Vit B12 & Folate Metabolism

Question 1

cobalamin

Answer 1

vit B 12

Question 2

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

Answer 2

T!

Question 3

Role of Vitamine B12

Answer 3

• DNA synthesis: tissue growth and regeneration
• maintenance of myelin sheath (B12 only)
• functions as a coenzyme: metabolism of homocysteine; methylmalonyl CoA metabolism

Question 4

hydroxocobalamin

Answer 4

mechanism involves rapidly removing cyanide (fires) from tissue by forming cyanocobalamin, which is then excreted unchanged in the urine

Question 5

dietary sources of B12

Answer 5

• eggs
• red meat and poultry
• milk and milk products
• some fortified cereals and meat substitutes

Question 6

Proteins involved in Vit B12 absorption and metabolism

Answer 6

• Haptocorrin (R protein or Transcobalamin I)
• Intrinsic factor
• Transcobalamin (II)

Question 7

Haptocorrin

Answer 7

• present in saliva

- delivers vit B12 to the duodenum

Question 8

Intrinsic Factor

Answer 8

• released from gastric parietal cells

- picks up vit B12 from duodenum for transport across the ileum

Question 9

Transcobalamin II

Answer 9

• from enterocytes

- main transporter of vit B12 to tissues

Question 10

causes of vitamin B12 deficiency

Answer 10

• 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

Question 11

What causes failed separation of B12

Answer 11

• hypochloridia in the stomach: increased pH results in inability to release B12
• vit B12 remains complexed with food or with haptocorrin

Question 12

Causes of lack of IF

Answer 12

• 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

Question 13

which cells produce IF?

Answer 13

parietal cells

Question 14

autoimmune disorder characterized by impaired absorption of vit B12 due to the lack of IF

Answer 14

Pernicious Anemia

Question 15

Progression of Pernicious Anemia

Answer 15

• 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

Question 16

Malabsorption of B12

Answer 16

• 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

Question 17

Diphyllobothrium latum

Answer 17

• fish tapeworm

- competes for B12 with IF

Question 18

overgrowth of bacteria that utilize vit B12 in stenotic loops of the intestine

Answer 18

Blind loop syndrome

Question 19

folic acid vs. folate

Answer 19

• folate = general term for all forms

- folic acid = synthetic form found in supplements

Question 20

What is Folate used for?

Answer 20

• DNA synthesis
• many metabolic functions: homocysteine metabolism, not for methylmalonic acid metabolism; metabolism of some amino acids and nucleotides
• neurological development of fetus

Question 21

dietary sources of folate

Answer 21

• leafy green vegetables
• legumes
• liver and red meat
• fortified cereals
• oranges and some fruits
• yeast

Question 22

cooking folate vs vit B12

Answer 22

Cooking folate can inactivate it, whereas B12 cooked is still gonna be there (eggs, meat, etc.)

Question 23

T or F. Folate is heat-stable

Answer 23

F! it is heat-labile

Question 24

Which has a higher rate of loss - Folate or Vitamin B12?

Answer 24

Folate! stores can be depleted in months!

Question 25

Process of Folate absorption and metabolism

Answer 25

- 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

Question 26

Causes of Folate deficiency

Answer 26

- inadequate intake: poor diet, overcooked foods, alcoholism - increased need - impaired absorption - impaired use: drug-induced - excessive loss through hemodialysis

Question 27

T or F. Both Vitamin B12 and Folate are involved in the synthesis of methionine from homocysteine

Answer 27

- Folate is the methyl group donor - vit B12 is the coenzyme for methyltransferase - further rxns take place which result in DNA synthesis

Question 28

T or F. Need folate in production of heme, not B12

Answer 28

F! need B12 for heme production

Question 29

Treatment for Vit B12 and folate deficiencies

Answer 29

- correct deficiency (iron concurrently given); quick recovery! - treat CAUSE of deficiency

Question 30

Lab tests for Vit B12 deficiency

Answer 30

- serum gastrin and gastric analysis - antibody assays: IF and parietal cells - stool analysis for parasites

Question 31

Symptoms of B12 and Folate deficiencies

Answer 31

- anemia - GI symptoms - Glossitis - neurological symptoms (B12 ONLY)

Question 32

Results of B12 and Folate deficiencies

Answer 32

- 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

Question 33

Screening tests for vit B12 and folate deficiencies

Answer 33

- CBC = decreased Hgb, pancytopenia w reticulocytopenia, high MCV, increased RDW - peripheral blood smear: macroovalocytes, hypersegmented neutrophils, tears, schistocytes, HJ bodies, basophilic stippling

Question 34

Confirmatory Testing for Folate and B12 defs

Answer 34

- serum vit B12 and Folate (immunoassay) - bone marrow examination: megaloblastic changes, nuclear-cytoplasmic asynchrony, decreased M:E ratio - methylmalonic acid levels - homocysteine levels