folate Flashcards
which is found in the body, folate or folic acid?
folate
which form is found in supplements and fortified foods, folate or folic acid?
folic acid
pteroylglutamate or pteroylglutamic acid is the chemical name for what vitamin?
folate
the number of forms of folate corresponds to the number of _____
glutamates (5-8)
where does the “action” happen in a folate molecule?
at the nitrogens
C units attach at N-5 and N-10 to form coenzyme forms
what needs to happen to folate in order for it to be in its coenzyme form
needs to be reduced (hydrogens get added to it)
what is needed in order to convert folate to its coenzyme form?
an enzyme (dihydrofolate reductase)
what is the coenzyme form of folate
THF (TETRAhydrofolate)
Tetrahydrofolate is the fully ______ state of folate
reduced
majority of food folates are _____
polyglutamates
since the majority of food folates are polyglutamates, what must happen to it before it can be absorbed?
What is the enzyme involved in this?
must be cleaved to mono-glutamate (one glutamate)
Folyl conjugase
list two ways drugs can compete with folate
- inhibit absorption
2. compete for transport
how is folate transported
using folate binding proteins identified in plasma and other tissues
where does folate get transported to?
to liver and other cells
how do cells store folate?
by adding back glutamates (POLY)
Folate metabolic role
- calling card of folate (THF)
- acceptor and donor of 1-carbon units
- important in :
- AA metabolism
- nucleotide metabolism
amino acid metablism WRT folate
1) methionine synthesis
- involves homocysteine (hcy to met)
- folate deficiency will build up homocsyteine
- also needs Vit B12
2) histidine metabolism
- basis for a folate deficiency test; FIGLU
3) interconversion of serine and glycerine
- serine-OH-methyltranferase
- also needs vit B6
all involve transfer of one carbon units
Folate and nucleotide metabolism
1) synthesis of purines and pyrimidines
- folate is needed
- DNA bases
- Purine: adenine, guanine
- Pyrimidine: uracil, thymine, cytosine
2) DNA synthesis
- crucial for cell division and growth
- folate acts as a coenzyme for enzyme involved in DNA synthesis
methotrexate
- chemotherapy drug
- inhibits dihydrofolate reductase
reduction in dihydrofolate means less THF, less nucelotide synthesis, less DNA , less cancer cell replication
folate food sources
- dark green vegetables
- corn, dried peas, beans, and lentils
- fortified products
- white flour, enriched pastas, corn meal
Folate deficiency
- usually due to diet
- could be due to drugs or malabsorption
- same anemia as Vit B12 deficiency
- megablastic/ macrolcytic anemia
- decreaed oxygen carrying capacity of blood
- weakeness, depression, increased homocysteine
- neural tube defects ..this is really remarkable about folate and very casia;
folate can mask a Vit B12 deficiency
if you have either a B12 or a folate deficiency, you will have macrocytic anemia
either will correct the anemia
so if u have inadequate B12 with adequate folate, you will NOT see the anemia
what test would you use to diagnose a folate deficiency
FIGLU test
also called a histidine load test
what is the process of a FIGLU test
-give excess histidine
-24hr urine collection
-measure FIGLU in the urine
-if high, then folate deficiency
refer to OH 16
what factors should you consider for folate requirements
- Vit B12 deficiency
- drug interactions
- women of child-bearing age; supplementation
- pregnancy
dietary folate equivalents
DFE=dietary folate equivalent
- food not the same as supplements
- food folate LESS bioavailable than supplemental folic acid because it is bound to other food components
- amount of folate depends on the source
- cant just say you need ___g folate…depends on source
Folic acid supplements and Neural tube defects
folic acid supplementation reduces risk of NTDs
who should supplement with folic acid
all women of child-bearing age…many pregnancies are unplanned
Folate can decrease cancer risk
DECREASE
- cancer; DNA damage»>DNA repair
- folate key role in DNA and RNA synthesis and methylation
- folate can contribute to genetic stability
- most evidence for colorectal cancer
what is the general relationships found in studies between folate and cancer
high folate, lower cancer
low folate, higher cancer
folate can increase cancer risk
folate can facilitate multiplication of cancer and pre-cancerous cells
-paradoxical acceleration of carcinogenesis
- core issues:
- timing of exposure
- level of exposure
- folate vs folic acid
Homocysteine is an intermediate of what AA metabolism?
methionine
homocysteine
is not present in diet
not incorporated into protein
associated with CVD
possible role in dementia/alzheimers
what are the 3 possible fates of homocysteine
- remethylation to methionine
- transsulfuration to cysteine
- release into circulation
what 3 vitamins are needed to metabolise homocysteine
folate
B6
B12
