Folate

Question 1

Dietary sources

Answer 1

Beans, nuts, meat (esp. organs), dairy, fruit, grain, cereal

Question 2

What amino acid does folate catabolize?

Answer 2

Histidine - transfers formimino group from formiminoglutamate to THF; results in formimino-THF and glutamate

Question 3

What compound will be elevated in the urine during folate deficiency?

Answer 3

Formiminoglutamate

Question 4

How does methotrexate work?

Answer 4

It is an anti-cancer drug that inhibits DHF reductase (traps DHF in cell), thus preventing THF formation that is needed to form thymidine. Cells can no longer divide quickly.

Question 5

Role of folate in DNA synthesis

Answer 5

Needed to form thymidylate (pyrimidine) and purines (adenine and guanine)

Question 6

Transmethylation role of folate

Answer 6

• Methylates homocysteine to methionine, which can then be used for various transmethylation reactions
• Methylaiton inactivates genes, which is important in development

Question 7

B12 role in methylation

Answer 7

Required for MS to work to methylate homocysteine and maintain SAM

Question 8

How does histone methylation work?

Answer 8

Methylation of chromatins turns off DNA, making DNA wrap tightly into histones. Removing methyl groups activates it, making it open. With insufficient SAM, genes will be turned on or off at the wrong time.

Question 9

What lipid transmethylation reactions is folate involved in?

Answer 9

Sterol methylation
- making hormones

Phospholipid methylation
- formation of phosphatidylcholine (PC) requires methylation
- needed to get lipids out of the liver; or else fatty liver occurs because lipids accumulate

Question 10

What does SAM methylate guanidinoacetate into?

Answer 10

Creatine

Question 11

How much food folate is equivalent to folic acid and what is a DFE?

Answer 11

1mcg folic acid = 1.7mcg food folate
DFE = 1mcg food folate or 1.7 X 1mcg folic acid (folic acid is more bioavailable)

Question 12

Requirements

Answer 12

M and F adults: 400mcg
Higher in pregnancy (600mcg DFE) and lactation (500mcg DFE)

Question 13

UL of folate

Answer 13

1mg/day folic acid
- High doses can mask B12 deficiency

Question 14

Food sources of folate

Answer 14

Plant and animal tissues - liver, dark green leafy veg, legumes
- Mostly found in polyglutamate form
- Mostly bound to proteins and storage polysacc
- Folic acid only found in fortified form

Question 15

What is the bioavailability of food folate?

Answer 15

<50% depending on poly- or mono-glu form
- Organic acid inhibit conjugase activity
- Folate is trapped in plant material
- Lost during food processing

Question 16

Absorption of folate

Answer 16

• Poly-glu folates cleaved to mono-glu folates by folate conjugase
• Peptidase converts mono-glu folates to THF (folic acid), which can be uptaken into cells by RFC (reduced folate carrier) and FBP (folate binding proteins) – just know that there are transporters and binding partners involved
• Recycled in bile by liver
• Circulates as mono-glu
• Stored as Poly-glu

Question 17

What B vitamins are involved in methylene tetrahydrofolate reductase?

Answer 17

Riboflavin and niacin

Question 18

Potential concerns of folic acid fortification of the food supply

Answer 18

• No toxicity has been reported
• Masking of B12 deficiency
• Potential increase in risk of colorectal cancer + other cancers

Question 19

How does folate deficiency/supplementation relate to cancer?

Answer 19

• Normal risk: folate deficiency may lead to increased chance of DNA mutations
• Adenoma (increased risk): folate deficiency may prevent progression to cancer, while supplementation may promote progression
• Cancer: folate deficiency may prevent cancer progression, while folate supplementation may increase cancer progression