B12 Folate Metabolism & Absorption Flashcards

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1
Q

Retarded synthesis of DNA due to B12 deficiency results in what?

A

Megaloblastic macrocytic anemia

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2
Q

What are the characteristics of megaloblastic macrocytic anemia?

A

Large erythroid precursors, ↓ mitotic divisions, delayed nucelar development, ↑ cytoplasmic volume

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3
Q

What is the clinical presentation of megaloblastic macrocytic anemia?

A

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

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4
Q

What are neurological symptoms of megaloblastic macrocytic anemia?

A

peripheral neuropathy (pins & needles, ↓ambulation, ↓memeory), “megaloblastic madness”

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5
Q

What is the dietary form of folate?

A

Dihydrofolate (DHF)

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6
Q

What is the active form of folate?

A

Tetrahydrofolate (THF)

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7
Q

What reduces DHF to THF?

A

Dihyrofolate reductase, adds 2* H⁺

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8
Q

What is the function of THF?

A

Transfer carbon units (CH₃) from donors to acceptors

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9
Q

Detail the folic acid pathway?

A

DHF + DHF reductase→ THF→ + N⁵,¹⁰-mehylene THF→ dUMP + C→ DHF & dTMP→ DNA

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10
Q

When does the main carbon transfer of folate metabolism?

A

Transfer of the carbon side chain of serine to N⁵,¹⁰-mehylene THF

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11
Q

Sources of DHF?

A

Most foods including eggs, milk, yeast & especially abundant in leafy vegetables

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12
Q

What are causes of folate deficiency?

A

Inadequate dietary intake (most common), malabsorption, pregnancy, drugs

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13
Q

Who are most likely to suffer from folic acid deficiency?

A

Poor & elderly, alcoholics

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14
Q

What are the folic acid requirements & how is it stored?

A

50 ug needed/day, 50-80% of ingested is absorbed in small intestine.
Liver stores 5-10 mg that can last 3-6 mths

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15
Q

What form of folate is found in circulation?

A

N⁵-mehyl-THF

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16
Q

What must happen to N⁵-mehyl-THF for it to enter the folic acid pathway?

A

Must be demethylated which requires vitamin B12 (cobalamin)

17
Q

What are the vitamin B12 (cobalamin) daily requirements & where do is come from?

A

3 ug/day

Comes from animal products, produced by stomach microorganisms

18
Q

What is responsible for 85% of B12 deficiencies?

A

Lack of intrinsic factor protein

19
Q

What is the function of intrinsic factor?

A

↑intrinsic factor→↑B12 absorption

20
Q

What is pernicious anemia and what causes it?

A

Form of megaloblastic macrocytic anemia caused by intrinsic factor & the cells that create it being destroyed

21
Q

How is the Shilling Test performed?

A

Oral radioactive B12 + B12 injection→ collect urine for 24 hrs→ intrinsic factor + oral radioactive B12 + B12 injection→ collect urine for 24 hrs

22
Q

How is the Shilling Test performed?

A

Oral radioactive B12 + B12 injection→ collect urine for 24 hrs→ intrinsic factor + oral radioactive B12 + B12 injection→ collect urine for 24 hrs

23
Q

After the Shilling Test what is the treatment?

A

If folate deficiency→ ↓junk food, ↑leafy vegetables.

If B12 deficiency→ B12 injections for life