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Vitamins - Water Soluble > Folate > Flashcards

Folate Flashcards

1
Q

Which B-vitamin plays a role in methylation?

A

Folate

folate is involved in methylation reactions because it is essential to the synthesis of methionine (from homocysteine) which is required for synthesis of SAM which is used in many methylation reactions

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2
Q

What B-vitamin deficiencies are associated with megaloblastic anemia?

A

Folate and B12

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3
Q

What are three key functions of folate in the body?

A
  1. the synthesis of DNA from thymidine and purines is dependent on folate coenzymes
  2. folate coenzyme is required for synthesis of methionine which is required to synthesis of SAM which is used in methylation reations including methylation of site on DNA and RNA
  3. folate is required for metabolism of several amino acids including:
    - systhesis of methionine from homocysteine (requires folate and B12)
    - histidine
    - serine
    - glycine
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4
Q

Active folate participates in the synthesis of which pyrimidine base?

A

thymine

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5
Q

A deficiency of either B12 or folate can be determined by what laboratory test?

A

deoxyuridine suppression test

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6
Q

Studies have shown that folate is protected from oxidative destruction by what vitamin?

A

vitamin C

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7
Q

The metabolism of serine, glycine, methionine and histidine all depend on the involvement of what vitamin?

A

folate

histidine metabolism requires THF
serine synthesis requires 5,10-methylene THF for synthesis from glycine
glycine may be synthesized from serine (reaction is reversible)
methionine regeneration from homocysteine requires folate as 5-methyl THF

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8
Q

Which B vitamin can mask a B12 deficiency?

A

folate

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9
Q

Which vitamin is more easily absorbed from supplements because the food form contains glutamic acid residues that must be removed by the digestive process?

A

folic acid

folate in foods exists primarily in the reduced form and usually contains up to nine glutamic acid residues

folic acid as supplements is highly available

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10
Q

Name good food sources of folate.

A 
mushrooms
green vegetables
peanuts
legumes
lentils
fruit
liver

raw foods are higher in folate because some folate is lost in cooking

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11
Q

What B vitamin is required by law to be fortified into food?

A

folic acid

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12
Q

Name all of the B vitamins that are involved in homocysteine metabolism.

A

folate (as THF)
B12
B6 (cystathionine synthase is PLP dependent)

betaine
(also called trimethyl glycine. Folic acid supplementation appears to increase betaine concentrations and betaine appears to be able to reduce plasma homocysteine concentrations in those with elevated blood levels

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13
Q

Prevention of cancer with optimal folate nutrition appears most promising for cancer in which tissue

A

colon

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14
Q

From the Teach-in presentations and Week 8 Discussion Wrap-Ups, list some therapeutic uses of one or a combination of B-vitamins.

A 
diabetes
osteoarthritis
schizophrenia
autism
hyperhomocysteinemia
depression
cognitive decline
migrane headaches
from Gaby Book
folate
atherosclerosis
hyperhomocysteinemia
stroke
psoriasis
dermatitis
vitiligo
ataxia
migraine
peripheral neuropathy
restless leg syndrome
autism
dementia/cognitive decline
depression
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15
Q

What are the forms of folate in the diet?

A

folate

  • form found naturally in foods
  • reduced form
  • contains up to 9 glutamic acid residues
  • over 150 different forms have been reported
  • forms most commonly found in foods 5-methyl THF, 10-formyl THF

folic acid

  • synthetic form
  • found in supplements and fortified foods
  • fully oxidized form
  • contains only one glutamate residue
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16
Q

What are the three parts of the folate molucule?

Why can’t humans make folate?

A
  1. pteridine
  2. PABA (pteridine + PABA = Pteroic Acid)
  3. glutamic acid (metabollically active folate has multiple glutamic acid residues attached.)

Humans lack the enzyme (a conjugase enzyme) to join pteridine and PABA to form Pteroic acid

17
Q

What are the coenzyme forms of folate?

A

Tetrahydrofolate - formed from two reductions of folate involving NADPH H+ (four H’s are added to folate)

5,10-methelene THF
5-methyl THF
5-formimino THF
10-formyl THF

other coenzyme forms are interchangeable

BUT 5-methyl THF can not be converted directly back to 5,10-methelene THF. B12 is required to convert 5-methyl THF back to THF (it donates a methyl group to cobalamin to create methylcobalamin as part of the reaction to convert homocysteine back to methionine. This is known as the folate trap.

18
Q

What is the RDA for folate?

A

400 mcg DFE

DFE = dietary folate equivalents

19
Q

What are DFE?

A

Dietary folate equivalents.

Used as a measure of folate for RDA.

1 DFE = 1 mcg natural folate = 0.6 mcg folic acid taken with food = 0.5 mcg folate taken on an empty stomach

20
Q

What are good food sources of folate?

A

mushrooms 21 mcg cooked

greens:
spinach 146 mg cooked, 194 mcg raw
broccoli
asparagus

legumes
strawberries 24 mcg
oranges

liver 260 mcg (but not other meats)

21
Q

Why is it good to eat some greens and fruits raw?

A

folate can be destroyed by heat, oxidation, and exposure to UV light

raw foods are typically higher in folate than cooked foods.

22
Q

What mineral is required for the absorption of folate?

A

Zinc

the carboxypeptidase enzyme that cleaves the glutamate tails from polyglutamate requires zinc to function

only monoglutamate forms of folate are absorbed

23
Q

What factors can interfere with folate absorption?

A
  1. zinc deficiency
  2. alcohol ingestion impairs digestion of folate so it is not in absorbable form
  3. Inhibitors in foods (legumes, cabbage, oranges)
  4. defects in proton-coupled folate transporter (PCFT) which is thought to be the primary transporter for folate absorption in the enterocyte. A hereditary defect in protein can result in folate malabsorption and severe folate deficiency.
24
Q

Does the body main stores of folate?

A

Yes. The liver stores about 1/2 of the body’s total folate.

Total body folate is about 11 to 28 mcg.

25
Q

What are the main functions of folate in the body?

A
  1. amino acid metabolism (single carbon methyl group transfer)
    - histidine
    - serine/glycine
    - methionine/homocysteine
  2. purine and pyrimidine synthesis
    - folate is essential for DNA synthesis
    - synthesis of cells with short life span like enterocytes and erythrocytes are particularly affected by folate deficiency
  • in purine synthesis, 10-formyl is needed for ring formation for adenine and guanine
  • in pyrimidine synthesis, 5,10-methylene THF required for synthesis of thymine
  • inadequate folate results in accumulation of uracil (and misincorporation of uracil in DNA instead of thymine)
26
Q

What is the role of folate in histidine metabolism?

A
  1. the final reaction in histidine metabolism (metabolism of formiminoglutamate - FIGLU) requires THF
  2. when folate is insufficient, FIGLU builds up and is excreted into the urine
  3. FIGLU is used as a measure of folate sufficiency
    - a oral dose of histidine is given then
    - urinary FIGLU is measured
    - the dose of histidine can alleviate the anemia caused by folate deficiency
27
Q

What is the role of folate in serine and glycine metabolism?

A
  1. a methyl group is transferred from serine to THF to create 5,10-methylene THF and glycine
  2. vitamin B6 is also required for this reaction
  3. the conversion of serine to glycine is reversible
28
Q

What is the role of folate in methionine metabolism?

A

Folate and B12 are required to regenerate methionine from homocysteine.

  1. 5-methyl THF donates a methyl group to cobalamin which is bound to the enzyme methionine synthase forming methylcobalamin.
  2. methylcobalamin donates a methyl group to homocysteine regenerating methionine.

This is called the Trans-methylation pathway.

29
Q

What nutrients other than folate can be used to convert homocysteine to other products?

A
  1. Betaine (trymethylglycine) can convert homocysteine directly to methionine.
  2. B6 is required by cystathionine beta-synthase to convert homocysteine to cystathionine in the Trans-sulfuration pathway. Cystathionine can then be converted to cysteine.
30
Q

What is the methyl-folate trap?

A

When vitamin B12 is deficiency 5-methyl THF can not be converted to other forms and accumulates in the cell. The cell can not use 5-methyl THF for DNA synthesis, so the lack of B12 creates a functional deficiency of folate.

5-methyl THF can not be converted directly back to 5,10-methelene THF. B12 is required to convert 5-methyl THF back to THF. When B12 is adequate, 5-methyl THF donates a methyl group to cobalamin to create methylcobalamin as part of the reaction to convert homocysteine back to methionine. This is known as the folate trap.

31
Q

What is the deficiency disease associated with folate deficiency?

A

megaloblastic macrocytic anemia

  1. characterized by large immature red blood cells that are reduced in number
    (MCV increased)
  2. signs and symptoms
    - fatigue
    - weakness
    - headaches
    - irritability
    - difficulty concentrating
    - shortness of breath
    - heart palpitations
32
Q

What if the progression of folate deficiency?

A

time of inadequate intake

  1. about 1 month - plasma folate levels low
  2. 3 to 4 months - red blood cell folate levels are reduced. Urinary FIGLU elevated.
  3. 4 to 5 months - rapidly dividing cells become megaloblastic (includes RBC and enterocytes); white blood cells become hypersegmented
33
Q

What groups of people may have increased need for folate or are at increased risk of folate deficiency?

A
  1. people with MTHFR C677T mutations.
  2. alcoholics - alcohol interferes with digestion of folate so it can not be absorbed.
  3. people with malabsorption disorders
  4. people taking drugs that interfere with folate metabolism
    - methotrexate (used to treat rheumatoid arthritis and cancer)
    - anticonvulsants (for epilepsy)
    - diuretics (for hypertension, increase folate excretion)
  5. women who may become pregnant (to prevent neural tube defects)
34
Q

Are there any risks from taking too much folate?

A

Yes. When large amounts of folic acid (the synthetic form are ingested).

Supplemental folic acid of 0.8 to 5 mg has been shown to increase the risk of some cancers.

35
Q

What tests can be used to assess folate status?

A
  1. serum or plasma folate
  2. RBC folate
  3. Homocysteine (may also be high due to B12 deficiency)
  4. FIGLU test (with histidine load)
  5. deoxyuridine suppression test (measures folate available for synthesis in thymidine in leukocytes. can also be used to test for B12 deficiency).
36
Q

What are three key functions of folate in the body?

A
  1. the synthesis of DNA from thymidine and synthesis of purines (adenine and guanine) is dependent on folate coenzymes
  2. folate coenzyme is required for regeneration of methionine from homocysteine (methionine is required to synthesis of SAM which is used in methylation reations including methylation of site on DNA and RNA)
  3. folate is required for metabolism of several amino acids including:
    - systhesis of methionine from homocysteine (requires folate and B12)
    - histidine
    - serine
    - glycine

Vitamins - Water Soluble (8 decks)

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