Folate Flashcards

Exam 1 (38 cards)

1
Q

What is the food form of folate and the type in the body?

A
  • folate
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2
Q

What is the supplement and fortified food form of folate

A

folic acid

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3
Q

Give an overview of folate

A
  • discovered as a growth factor in green leafy veg “foliage”
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4
Q

are there more than 1 form of folate

A
  • yes, there are numerous forms of folate, # glutamates (5-8)
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5
Q

What is involved in folate structure?

A
  • glutamate
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6
Q

What needs to happen in order for folate to be absorbed?

A
  • in order for folate to be absorbed it needs to get to the mono glutamate form
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7
Q

Explain folate absorption

A
  • majority of food folates are POLYglutamates
  • must be cleaved to mono-glutamate for absorption (folyl conjugASE)
  • allows folate to be absorbed
  • many drugs compete with folate (inhibit absorption, compete for transport)
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8
Q

Where does carbon transfer in folate occur

A
  • happens at nitrogens (N-5 and N-10)
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9
Q

Explain folate transport

A
  • folate binding proteins
  • identified in plasma and other tissues
  • bind folate with high-affinity
  • transports folate to liver and other cells
  • cells store folate by adding back glutamates (POLY)
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10
Q

What is flolates coenzyme form?

A
  • Tetrahydrofolate (THF)
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11
Q

Give an overview of THF

A
  • folates co-enzyme form
  • fully reduced state
  • must be in this form to carry carbon units and preform metabolic role
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12
Q

What must happen to folate in order to preform metabolic roles

A
  • needs to be converted to its coenzyme form
  • activated by reductions (add hydrogens) - added to positions 5,6,7,8,
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13
Q

Explain break down to folates coenzyme form

A
  • folate –> dihydrofolate (DIF) –> Tetrahydrofolate (THF)
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14
Q

Which vitamin adds H to folate?

A
  • Niacin
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15
Q

How many different One carbons are added to THF?

A
  1. N^5-formyl THF
  2. N^5-formimiNO THF
  3. N^5-methyl THF (circulating form)
  4. N^10- formyl THF
  5. N^5,10-methylene THF
  6. N^5,10- methenyl THF
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16
Q

What is folates metabolic roles?

A
  1. Single carbon metabolism
  2. Amino acid metabolism
  3. Nucleotide metabolism
17
Q

Explain single carbon metabolism

A
  • calling card for THF
  • acceptor and donor of 1-carbon units
  • important in: 1. amino acid metabolism & 2. nucleotide metabolism
18
Q

Explain amino acid metabolism

A
  1. Methionine synthesis
    - involves homocysteine (hay to met)
    - folate deficiency will build up homocysteine
    - also needs vitamin B12
  2. histidine catabolism
    - basis for a folate deficiency test; FIGLU, LOAD test
  3. interconversion of serine and glycine
    - serine-OH-methyltransferase
    - also needs vitamin B6
19
Q

Explain Nucleotide metabolism

A
  1. synthesis of purines and pyrimidines
    - heterocyclic nitrogenous compounds
    - purine and pyrimidine bases
    - allows for synthesis of nucleosides and nucleotides
    - EX: ATP
  2. DNA synthesis
    - needed for DNA synthesis
    - crucial for cell division and cell growth
    - All involve transfer of one-carbon units
20
Q

What is methotrexate

A
  • chemo drug
  • inhibits DHFR (dihydrofolate reductase) and causes:
  • less THF
  • less nucleotide synthesis
  • less DNA
  • Less cancer cell replication
21
Q

What are folate food sources.

A
  • dark green veg
  • corn, dired peas, bean, lentils
  • fortified products: white flour, enriched pastas, corn meal
22
Q

What is folate deficiency due to

A
  • diet
  • drugs or malabsorption
  • same anemia as B12 deficiency megaloblastic/macrocytic anemia, decreased oxygen carrying capacity of blood(red blood cells)
23
Q

What are the symptoms of folate deficiency

A
  • weakness, depression
  • increased homocysteine
  • neural tube defects (birth defects)
24
Q

What can folate mask?

A
  • B12 deficiency
  • if you have a B12 deficiency you will have megaloblastic anemia
  • if you have a folate deficiency you will have the same anemia
  • either will correct the anemia; if you have inadequate vitamin B12 with adequate folate you will NOT see the anemia
25
How do you diagnose folate deficiency
- FIGLU test
26
What is the FIGLU test
- aka " histidine load test" - method to diagnose folate deficiency
27
how does the FIGLU test work?
- give excess histidine (15 g) because you want histidine in plenty of supply so it can be used for what it is needed. - 24 hour urine collection or blood sample - measure FIGLU in the urine or blood - If high then folate deficiency (look at what builds up)
28
What are the folate requirements factors
- B12 deficiency - drug interactions - women of child-bearing age supplementation - pregnancy
29
What are the dietary folate equivalents (DEF)
- 1 microgram --> 1 microgram DFE - 1 microgram supp folic acid with food ---> 1.7 microgram DEF - 1 microgram sump folic acid empty stomach --> 2.0 microgram DEF
30
What is the bioavailibity ranking of DFE
1. supplemental folic acid on empty stomach 2. fortified food (supplemental folic acid with food) 3. folate food
31
Why is folate from food the lowest bioavaility ranking
- bound to other food components
32
Explain folate and NTD
- folate supplementation reduces risk of neural tube defects - all women of child-bearing age should supplement with folic acid - major public health issue
33
What are disadvantages of folic acid fortification
- making of B12
34
What diseases does folate decrease?
- cancer; DNA damage - folate plays a key role in proper DNA and RNA synthesis and methylation - Folate can contribute to genetic stability - Folate intake related to decreased cancer risk - most evidence for colorectal cancer
35
How can folate increase cancer risk
- can facilitate multiplication of cancer and pre-cancerous cells - cancer cells have a high rate of proliferation - cancer cells need folate to maintain thymidine synthesis at a pace needed to maintain the high rate of DNA synthesis - Any cancer is susceptible to this phenomenon - paradoxical acceleration of carcinogenesis
36
What are the core issues of folate and cancer risk
- timing of exposure --> damage - know how to get rid of it - level of exposure --> folate from food or acid - form of exposure (folate vs folic acid)
37
What is homocysteine
- intermediate of methionine metabolism - not present in the diet - not incorporated into protein - associated with CVD - possible role in dementia/alzeimers
38
What are the 3 possible fates of homocysteine
1. remethylation to methionine (needs folate, B12, choline) 2. transsulfuration to cysteine (needs B6) 3. release into circulation