Which B-vitamin plays a role in methylation?
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
What B-vitamin deficiencies are associated with megaloblastic anemia?
Folate and B12
What are three key functions of folate in the body?
- the synthesis of DNA from thymidine and purines is dependent on folate coenzymes
- 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
- folate is required for metabolism of several amino acids including:
- systhesis of methionine from homocysteine (requires folate and B12)
- histidine
- serine
- glycine
Active folate participates in the synthesis of which pyrimidine base?
thymine
A deficiency of either B12 or folate can be determined by what laboratory test?
deoxyuridine suppression test
Studies have shown that folate is protected from oxidative destruction by what vitamin?
vitamin C
The metabolism of serine, glycine, methionine and histidine all depend on the involvement of what vitamin?
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
Which B vitamin can mask a B12 deficiency?
folate
Which vitamin is more easily absorbed from supplements because the food form contains glutamic acid residues that must be removed by the digestive process?
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
Name good food sources of folate.
mushrooms green vegetables peanuts legumes lentils fruit liver
raw foods are higher in folate because some folate is lost in cooking
What B vitamin is required by law to be fortified into food?
folic acid
Name all of the B vitamins that are involved in homocysteine metabolism.
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
Prevention of cancer with optimal folate nutrition appears most promising for cancer in which tissue
colon
From the Teach-in presentations and Week 8 Discussion Wrap-Ups, list some therapeutic uses of one or a combination of B-vitamins.
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
What are the forms of folate in the diet?
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
What are the three parts of the folate molucule?
Why can’t humans make folate?
- pteridine
- PABA (pteridine + PABA = Pteroic Acid)
- 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
What are the coenzyme forms of folate?
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.
What is the RDA for folate?
400 mcg DFE
DFE = dietary folate equivalents
What are DFE?
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
What are good food sources of folate?
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)
Why is it good to eat some greens and fruits raw?
folate can be destroyed by heat, oxidation, and exposure to UV light
raw foods are typically higher in folate than cooked foods.
What mineral is required for the absorption of folate?
Zinc
the carboxypeptidase enzyme that cleaves the glutamate tails from polyglutamate requires zinc to function
only monoglutamate forms of folate are absorbed
What factors can interfere with folate absorption?
- zinc deficiency
- alcohol ingestion impairs digestion of folate so it is not in absorbable form
- Inhibitors in foods (legumes, cabbage, oranges)
- 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.
Does the body main stores of folate?
Yes. The liver stores about 1/2 of the body’s total folate.
Total body folate is about 11 to 28 mcg.
