B12 Folate Metabolism & Absorption Flashcards
Retarded synthesis of DNA due to B12 deficiency results in what?
Megaloblastic macrocytic anemia
What are the characteristics of megaloblastic macrocytic anemia?
Large erythroid precursors, ↓ mitotic divisions, delayed nucelar development, ↑ cytoplasmic volume
What is the clinical presentation of megaloblastic macrocytic anemia?
MCV >100
Lethargy, weakness, yellow or waxy pallor, loss of weight & appetite, diarrhea
Blood smear: many enlarged oval macrocytes
Bone marrow: large erythroblasts (megaloblasts), neutrophils w/ >5 lobes
What are neurological symptoms of megaloblastic macrocytic anemia?
peripheral neuropathy (pins & needles, ↓ambulation, ↓memeory), “megaloblastic madness”
What is the dietary form of folate?
Dihydrofolate (DHF)
What is the active form of folate?
Tetrahydrofolate (THF)
What reduces DHF to THF?
Dihyrofolate reductase, adds 2* H⁺
What is the function of THF?
Transfer carbon units (CH₃) from donors to acceptors
Detail the folic acid pathway?
DHF + DHF reductase→ THF→ + N⁵,¹⁰-mehylene THF→ dUMP + C→ DHF & dTMP→ DNA
When does the main carbon transfer of folate metabolism?
Transfer of the carbon side chain of serine to N⁵,¹⁰-mehylene THF
Sources of DHF?
Most foods including eggs, milk, yeast & especially abundant in leafy vegetables
What are causes of folate deficiency?
Inadequate dietary intake (most common), malabsorption, pregnancy, drugs
Who are most likely to suffer from folic acid deficiency?
Poor & elderly, alcoholics
What are the folic acid requirements & how is it stored?
50 ug needed/day, 50-80% of ingested is absorbed in small intestine.
Liver stores 5-10 mg that can last 3-6 mths
What form of folate is found in circulation?
N⁵-mehyl-THF
What must happen to N⁵-mehyl-THF for it to enter the folic acid pathway?
Must be demethylated which requires vitamin B12 (cobalamin)
What are the vitamin B12 (cobalamin) daily requirements & where do is come from?
3 ug/day
Comes from animal products, produced by stomach microorganisms
What is responsible for 85% of B12 deficiencies?
Lack of intrinsic factor protein
What is the function of intrinsic factor?
↑intrinsic factor→↑B12 absorption
What is pernicious anemia and what causes it?
Form of megaloblastic macrocytic anemia caused by intrinsic factor & the cells that create it being destroyed
How is the Shilling Test performed?
Oral radioactive B12 + B12 injection→ collect urine for 24 hrs→ intrinsic factor + oral radioactive B12 + B12 injection→ collect urine for 24 hrs
How is the Shilling Test performed?
Oral radioactive B12 + B12 injection→ collect urine for 24 hrs→ intrinsic factor + oral radioactive B12 + B12 injection→ collect urine for 24 hrs
After the Shilling Test what is the treatment?
If folate deficiency→ ↓junk food, ↑leafy vegetables.
If B12 deficiency→ B12 injections for life
