5 Folate Flashcards
Folate aka
Folacin Folic Acid (supplement / fortified name)
Folate named when
Folate in foods or body
folate chemical name
pteroylglutamate or pteroylglutamic acid
Folate structural features
Pteroic Acid + glutamate
C units attach where on folate for coenzyme form? ***
N-5 and N-10 ***
Folate activated by what reaction
reduction
- added hydrogens to 5,6,7,8 positions
Folate reductions
folate –> dihydrofolate (DHF) –> tetrahydrofolate (THF)
THF fully reduced form
What vitamins reduces (adds H) to folate?
Niacin NADH
tetrahydrofolate multiple forms formed by? what is the circulating form?
6 different forms made by addition of one carbon units
(must be in THF form to add carbon units)
N5-methyl THF = circulating form
Folate circulating form
N5-methyl THF
Majority of food folates are
polyglutamates
Necessary process to absorb folate
polyglutamates food form
- cleaved to monoglutamate to be absorbed
Drugs and folate
inhibit absorption
compete for transport
Folate uses what in order to travel
binding proteins
many water soluble proteins use this
Folate short term storage in cells by
adding back glutamates (polyglutamate)
Folate metabolic role
THF
acceptor of 1 carbon units
1. AA metabolism
2. nucleotide metabolism
Folate amino acid metabolism
- Methionine synthesis (hcy –> met)
- Histidine catabolism
- interconversion of serine + glycine
Folate deficiency test
role of histidine metabolism
FIGLU
Folate Nucleotide metabolism
- synthesis of purines and pyrimidines (adenine, guanine, uracil, thymine, cytosine)
- DNA synthesis
Methotrexate
chemotherapy drug
slows conversion of DHF to THF
Folate food sources
Dark green vegetables
Corn, dried peas, beens, lentils
Fortified in white flour, corn meal, rich pastas
Folate deficiency symptoms
Macrocytic anemia (same as B12)
- decreased oxygen carrying capacity of blood
- weekness, depression
*increased homocysteine Hcy
Neural tube defects
Folate and b12
Same macrocytic anemia with deficiency
- Increasing folate will correct this but not the neurological effects of b12 deficiency
Diagnosing Folate deficiency
Histidine Load test (FIGLU test)
- Give excess histidine, measure FIGLU in urine after 24hrs
- High than folate deficiency
Folate vs Folic Acid (supplement form)
Folate LESS bioavailable
approximately 2:1 (on empty stomach)
Neural Tube Defects occur? prevented?
21-28 days post conception (before knowledge of pregnancy)
Folic acid supplementation
Folate Fortification Debate
important for women becoming pregnant, not so much others
can increase cancer risk
Folate and caner
Contribute to genetic stability (lowers colorectal cancer)
- proper function of Wnt cascade
Cancer cells need folate to maintain “tymidine synthesis” at a pace needed to maintain high rate of DNA synthesis
- paradoxical acceleration of carcinogenesis
Core issues (large area of study):
- timing of exposure
- level of exposure
- folate versus folic acid
Current interest around folate stems around discovery of ?
Importance?
Single nucleotide polymorphism
- alternations in genes coding for folate dependent enzymes (5,10-methylene THF reductase “MTHFR”)
Increase risk of disease (Neural tube defect and breast cancer)
Would B12 fortification help folate def?
Neural tube defects helped with B12
B12 fortification would not solve malabsorption problem
Large area of study. Still unknown
Homocysteine an intermediate of
Methionine metabolism
Diseases associated with homocysteine
CVD
- possible dementia/alzheimers
3 Homocysteine fates?
Needs?
Good:
remethylation to methionine (B12)
Transsulfeation to cysteine (B6)
Bad:
Release to blood
folate, b6 and b12
