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NHM 561 > Folate (7 questions) > Flashcards

Folate (7 questions) Flashcards

1
Q

What are the CoE. forms of FOLATE?

A

DHF
THF
5-Formyl THF
10-Formyl THF
5,10-Methenyl THF
5,10-Methylene THF
5-Methyl THF

(7 total)

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2
Q

How are RDAs for folate expressed?

A

DFEs

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3
Q

DFE

A

Dietary Folate Equivalents

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4
Q

What is the DFE for FOLATE?

A

1 mcg DFE = 1 mcg from food FOLATE

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5
Q

What is the DFE for FOLIC ACID?

A

1 mcg DFE = 0.6 mcg FOLIC ACID

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6
Q

What is the DFE for FOLIC ACID from dietary supplements taken on an empty stomach?

A

1 mcg DFE = 0.5 mcg FOLIC ACID (very high bioavailability)

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7
Q

What is the difference between FOLATE and FOLIC ACID?

A

FOLATE = the form from natural food sources (green leafy vegetables); reduced form

FOLIC ACID = form from fortified foods (flours, breakfast cereals) or supplements; oxidized form

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8
Q

Why is FOLATE more difficult to digest?

A

2 reasons why folate absorption is impeded:

  1. FOLATE has very long tails of GLUTAMIC ACIDS
  2. Reduced form
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9
Q

What is the bioavailability of FOLATE?

A

50% naturally present form

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10
Q

What is the bioavailability of FOLIC ACID?

A

~85% when taken with food

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11
Q

What are the best food sources of folate?

A
  1. Beef liver
  2. Spinach, boiled
  3. Black-eyed peas
  4. Breakfast cereals
  5. Green vegetables (asparagus, Brussels, lettuce, etc)

Also, fortified grains

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12
Q

(T/F) There is a federal fortification of folate.

A

TRUE, since 1998.

140 micrograms folic acid per 100g product
FOLIC ACID MONOGLUTAMATE is the fortified form (it’s oxidized, so very easily absorbed)

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13
Q

What is the formula for calculating DFEs?

A

mcg DFE = mcg naturally occurring folate + (1.7 x mcg folic acid)

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14
Q

Example 1: Calculating DFEs

A serving (85g) of frozen spinach contains 120 mcg of folate. What is the DFE?

A

Folate (mcg DFE) = 120 mcg x 1
120 mcg DFE

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15
Q

Example 2: Calculating DFEs

A serving (40g) of ready-to-eat breakfast cereals contains 200 mcg folic acid. What is the DFE?

A

Folate (mcg DFE) = 200 mcg x 1.7
340 mcg DFE

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16
Q

Example 3: Calculating DFEs

A serving (30g) of enriched wheat flour contains a combination of naturally occurring folate (5 mcg) and folic acid (50 mcg). What is the DFE?

A

Folate (mcg DFE) = (5 x 1) + (1.7 x 50)
90 mcg DFE

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17
Q

(T/F) Folic acid from supplements and fortification do not need to undergo digestion and are readily absorped.

A

TRUE

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18
Q

FILL IN THE BLANK

Folate naturally found in food is in XXXXXXXXXX form and must be digested to XXXXXXXXXX form.

A

POLYGLUTAMATE FORM

MONOGLUTAMATE FORM

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19
Q

What 2 enzymes are needed for folate absorption?

A

CARBOXYPEPTIDASES are needed to hydrolyze (“remove”) the polyglutamate tail from folate to allow for absorption:

  1. Soluble carboxypeptidase
  2. Enzyme bound to brush border membrane
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20
Q

Soluble carboxypeptidase

A

From pancreatic juices and bile secreted into the jejunum

Needed to hydrolyze polyglutamate tail from folate for absorption

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21
Q

Enzyme bound to brush-border membrane

A

Contributes to digestion/absorption more than soluble form

—It is zinc-dependent and requires a HIGHER pH (more basic) in the duodenum (thanks to bicarbonate from the pancreas)
—It is inhibited by ETOH ingestion and certain foods (legumes, lentils, cabbage, and oranges)

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22
Q

(T/F) Dietary supplements of folate are inhibited by the ingestion of ETOH due to the enzyme bound to brush-border membrane.

A

FALSE

Only natural forms of folate require the two carboxypeptidases enzymes to hydrolyze the polyglutamate tail from folate to allow for absorption

The enzyme bound to brush-border membrane is inhibited by ETOH and certain foods (lentils, legumes, oranges, and cabbage)

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23
Q

Proton-coupled folate transporter

A

A high affinity folate carrier expressed in proximal jejunum and duodenum

Facilitates the transport of folic acid and folate into the enterocytes

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24
Q

What happens once folate and folic acid are in the enterocyte?

A

Once folate enters the CYTOPLASM of the cell, it is going to be reduced by dihydrofolate reductase to DHF, then THF with NADPH and reductase enzyme

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25
Q

How does folate leave the enterocyte?

A

THF will bind with a folate binding protein and be transported outside of the enterocyte, VIA MRP3

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26
Q

MRP3

A

An active-carrier dependent Multi-drug Resistant Protein 3, that binds THF to transport folate outside the enterocyte

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27
Q

What CoE. form will folate be in portal circulation?

A

5-methyl THF, OR
DHF, OR
the formulated forms as well.

It will be monoglutamated

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28
Q

RFC

A

Reduced Folate Carriers; ubiquitously expressed

Facilitates carrier-mediated uptake into the liver (majority) and other tissues

29
Q

FOLR1

A

Folate Receptor Alpha; expressed in brain

Note defects in gene are associated with neurological disorders

30
Q

What are the forms of folate in hepatocytes and other cells? What is the breakdown?

A

~33% THF
~33% 5-methylTHF
~33% 5- or 10- formyl THF

31
Q

How is folate trapped in cells?

A

Once in the cell, it will be converted to the polyglutamate form, trapping it into the cell

32
Q

Polyglutamate synthetase

A

Enzyme that catalyzes the addition of 4-8 glutamate / glutamic acids

Requires ATP

Traps folate within the cell

33
Q

Gamma-glutamyl hydrolase

A

Enzyme that removes glutamate residues prior to folate exiting the cell

34
Q

FILL IN THE BLANK

In systemic circulation, folate is in XXXXXXXXXX form.

A

Monoglutamate form
—~1/3 free
—~2/3 bound to protein (albumin, alpha 2 macroglobulin, and high-affinity folate binding protein)

In THF, 5-methylTNF or 10-formylTHF

35
Q

How much folate is stored in the body? Where?

A

7 to 30 mg stored

50% in the liver, in THF and 5-methyl THF polyglutamate forms

36
Q

(T/F) When folate is trapped inside the cell, it’s typically also bound to some type of folate-binding protein. This will keep it anchored into the cell, as well as the polyglutamate tail.

A

TRUE

37
Q

Folate CoE. forms function in which 2 types of reactions?

A
  1. Nucleotide biosynthesis
  2. Methylation of AA
38
Q

How does THF form THF derivatives?

A

THF accepts one-carbon groups

THF derivatives then serve as donors of one carbon units in a variety of biosynthetic reactions

39
Q

Folate is critical for…..

A

pyrimidine synthesis of DNA

40
Q

What are the 3 pyrimidines?

A

1) Cytosine

2) Uracil

3) Thymine

41
Q

Pyrimidine

A

The base

Will be converted to CYTOSINE (which is used for RNA and DNA biosynthesis)

42
Q

(T/F) The base uracil can be converted to thymine.

A

TRUE, when the body needs to make DNA

43
Q

Uracil

A

ONLY used in RNA

44
Q

Thymine

A

ONLY used in DNA

45
Q

dUMP

A

DeoxyURIDINE monophosphate; used in RNA synthesis

Can be converted to dTMP

46
Q

dTMP

A

DeoxyTHYMINE monophosphate; used in DNA synthesis

47
Q

Thymidylate synthetase

A

An enzyme that requires folate (as N5, N10-methylene THF)***

So in this reaction, a methyl group is going to be added, when uracil —–> thymine

48
Q

(T/F) The dUMP —> dTMP reaction can take place without folate.

A

FALSE

If there is a deficiency of folate, this reaction cannot take place.

49
Q

What is the consequence of utilizing uracil for DNA synthesis?

A

When there is a deficiency of the CoE form (5-, 10-methyleneTHF), the body will use URACIL into the DNA instead of using thymine, which causes all kinds of problems.

This is considered an AP site (pre-mutagenic apyrimidinic site), which can lead to:
—DNA strand breaks
—DNA fragmentation
—or, the cell can recognize this as an anomaly, can the cell will go through APOPTOSIS (cell suicide)

This accumulation of DNA damage could result in pre-cancerous changes.

50
Q

What CoE. form is required for the biosynthesis of purines? ***

A

10-formyl THF form

51
Q

What are the 2 purines?

A

1) Adenine

2) Guanine

Both used in DNA and RNA

52
Q

Explain the process for dUMP —–> dTMP when there is not a folate deficiency present.

A

5-,10-methylene THF is going to be used for the dUMP —-> dTMP reaction. With thymidylate synthetase being required.

The 5,10-methylene THF is going to donate the methyl groups, and then be converted back to DHF

53
Q

What is the base, that will be converted to adenine and guanine? **

A

INOSINE MONOPHOSPHATE (IMP) **

The biosynthesis of IMP is extremely important because it REQUIRES FOLATE; specifically, the 10-formyl THF form

54
Q

(T/F) The body must biosynthesis purines every time it needs to make RNA and DNA.

A

FALSE. There are salvage pathways, so when the body breaks down old DNA and RNA, it can reuse these purines.

55
Q

De Novo Synthesis

A

Meaning “FROM THE NEW”

In reference to the biosynthesis of purines

An example would be a child who is rapidly growing, or during a growth spurt, they are going to need de novo purine biosynthesis, and it is VERY critical.

It is not a concern for older adults

56
Q

What CoE. form is required to convert glycine <—–> serine?

A

5, 10-methylene THF (also used in dUMP to dTMP)

57
Q

Serine hydroxymethyltransferase

A

PLP-dependent enzyme (B6 COENZYME**) that converts 5, 10-methylene THF <—->THF in the reaction: Glycine <——-> Serine

Note: this is a reversible reaction

58
Q

Explain folate’s role in homocysteine metabolism.

A

5-methyl THF is going to be picked up by the enzyme METHIONINE SYNTHASE, and is going to take that methyl group, and add it to COBALAMIN, so now we have METHYLCOBALAMIN. This converts 5-methyl THF —> THF, allowing THF to go through the glycine <—-> serine reaction, via SERINE HYDROXYMETHYLTRANSFERASE.

59
Q

Explain how SAM plays a role in the methylation of DNA.

A

SAM donates a methyl group to CYTOSINE, creating 5-methylcytosine.

60
Q

DNA methyl-transferase

A

Enzyme in the reaction of converting cytosine —> 5-methylcytosine

61
Q

Where is the methyl group on 5-methylcytosine, originally come from? ***

A

Initially this methyl group came from 5-methyl THF, then given to B12, creating methylcobalamin, then given to methionine, and then converted to SAM, and now it’s going to be provided here to make DNA.

**AKA: IT STARTED OUT AS PART OF FOLATE

62
Q

How does methylation play an important role in gene expression?

A

The importance of the methyl groups getting added to cytosine is seen here.

If the DNA is wrapped around histones (DNA spools), and the brown spots are methylated cytosines, it keeps the DNA tight and wrapped up. So the DNA cannot be accessed and transcription of DNA cannot occur.

When methylation is removed, the spooling becomes much looser and DNA can now be accessed by other enzymes that CAN go through gene transcription. So gene expression is going to be increased

It is all involved with 5-methyl THF bc that’s where the methyl group originated from.

63
Q

Folate Deficiency

A

Megaloblastic macrocytic anemia (very common)
—fewer than normal RBCs, that are large and immature, oval-shaped

64
Q

What types of cells are likely to be affected by folate deficiency?

A

Rapidly-dividing cells, such as 1) enterocytes, and 2) blood cells

65
Q

How does folate deficiency present, clinically?

A

MCV increases and hypersegmentation of WBCs occur, due to:

Impaired DNA synthesis, negatively effecting GI cells and snowballing into impaired nutrient absorption of other vitamins and minerals.

-Glossitis and bright red tongue, swelling (in severe deficiencies)
-Spina bifida and neural tube defects

66
Q

What is the upper tolerable intake for folate, in adults? Why?

A

1 mg for folic acid supplementation of fortified foods, because folic acid supplements can mask potential B12 deficiency associated with megaloblastic anemia but not neurological damage

67
Q

FILL IN THE BLANK

Intakes of folate higher than XXXXXX times recommendations may be associated with increased cancer risk and cancer mortality (especially in those with pre-cancerous tumors). Why?

A

2.5x higher

Because of folate’s ability to be utilized in the synthesis of DNA. So, in those with cancers that are rapidly growing tissues, we do not want that to happen, and so increased intake of folate can actually drive cancer growth in that way.

68
Q

How is folate assessed?

A

Plasma folate concentrations (3 to 20 mcg/L). Below 3 = deficiency. This indicates the short-term status of folate

RBCs folate <140 mcg/L considered deficient. This indicates the long-term status of folate because RBCs live for 120 days.

NHM 561 (21 decks)

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