folate Flashcards
folate is the “Factor” present in yeast and liver that cured what in who
anaemia in pregnant women
folate is isolated from what and names after what
Isolated from spinach and named after the Latin for foliage (folia)
folate is a group of chemically related what, with related what
chemically-related vitamers with related activities (pteroylglutamic acid)
what does folates structure comprise of
a pteridine ring coupled to para-aminobenzoic acid (pABA)
how do vitamers differ
they differ in the oxidation state of the aromatic ring, the type of 1-C units at N5 and N10 and variable number of glutamic acids attached to the pABA
what cycle is folate key to
folate cycle
whats the importance of folate in the folate cycle
Donates methyl groups to homocystine to make methionine
So need folate to allow normal nucleic acid function
folates One Carbon [1-C (methyl)] transfer & methionine metabolism, are substrates and coenzymes for what
for 1-C reactions (e.g. important for DNA and protein synthesis)
what is folate function key to
methionine synthesis, via homocysteine (tHcy) metabolism, related to that is the production of S-adenosylmethionine (SAM)
DNA synthesis (2x purines and pyrimidine); key converiosns its involved with is the conversion of dUTP to dTMP
DNA methylation, gene and protein expression
choline synthesis (lipid metabolism, membranes and synthesisng neurotransmitters)
formate catabolism to CO2 and elimination (toxicity) – do detoxifies formate
conversion of serine to glycine (both of those are required for protein synthesis)
One Carbon [1-C (methyl)] transfer & methionine metabolism
These are Substrates and coenzymes for 1-C reactions (e.g. important for DNA and protein synthesis)
what percentage of population is clinically folate deficient
10%
what percentage of 15-18 year olds have marginal folate status
40%
what % of women do not achieve RDA (RNI) even accounting for supplement use
84-92%
folate deficiency is common in what age group
> 65y especially institutionalised elderly – eg in care home environment
explain pregnancy and neural tube defects(NTD) in terms of folate
600mg/day recommended for women who could become pregnant
84-92% women do not achieve this even with supplements (50% pregnancies unplanned)
high dose folic acid reduces risk of second NTD birth by 50-75%
explain the link between vascular disease and folate
high folate intake associated with 35% reduced risk of CVD – cardio vascular disease (reduced levels of homocysteine)
explain the link between folate and cancer
poor folate status increases risk of cancer of cervix, lung, pancreas, breast and colon (25%) [note suggested detrimental effect of high doses of folic acid (used in supplements)causing colorectal cancer]
explain the link between folate and dementia and cognitive impairment
low folate (and B12; note ‘folate trap’) associated with depression, dementia and poor cognition commonly seen in elderly
what does tetrahydro refer to in folate structure
refers to the hydrogen atoms it has. What changes is the group its carrying
what are methylene groups structure written as
CH2
what are methane group structure written as
CH3
in folate what form is used in fortification and supplementation and why
acid form not folate form
Folate form isn’t suitable for supplements as doesn’t survive long whereas folic acid does
Folates present in foods as what
polyglutamates (50-75% of what consume
has folate in polyglutamate form)
what are the 4 predominant naturally occurring folates in food
THF, DHF, formyl- and methyl
THF – tetra hydro folate
DHF – dihydrofolate
5-methyl THF comprises most of the folate in what
in foodstuffs and
circulating form in plasma
what are the richest natural sources of folate
green leafy vegetables (spinach, broccoli, B.sprouts)
liver, yeast, whole wheat, nuts, beans
wholegrain cereals, vegetables and beverages (fruit juices & milk) main contributors in UK
Brassicas and green leafy veg are good sources of folate
Animal products are less rich in folates compared to plant products
Microbes like yeast can synthesis folates. So yeast based products contain folate
what percentage of our folate daily intake is from veg excluding potatoes
15%
what percentage of of food folates bioavailable
20-50%
is folate or folic acid more bioavailable
synthetic folic acid is more bioavailable
what folate is in milk
Monoglutamates in milk (easily absorbed)
explain food folates that are oxidisable
accurate measurement difficult (tri-enzyme;
extracted & hydrolysed to monoglutamates)
underestimation in food composition tables
Destroyed by heating (boiling v microwave)
Unstable during long-term storage
Oxidised (stable) folic acid (fortified foods and dietary supplements)
what vitamin is folate and what propertys does it have
is water-soluble and a B vitamin and has same problems as them such as that its destroyed by heat, so microwave rather than boil. It also leaches out of substances. Unstable due to sensitivity to oxygen so why folate isn’t used in supplements etc
whys liver a good folate source
as it stores folate
folates total body pool=
approx. 7.5 mg (but can be as high as 30 mg depending on diet)
Depletion studies suggest absolute requirement of what
80-100 µg/day
RNI set at what in men and women
200 µg/day
explain how much additional intake is required for women planning pregnancy and why and concerns over this
additional 400 µg/day for women planning a pregnancy (prevention of NTDs) is unachievable by diet alone (liver concentrated source; vitamin A teratogenic)
Supplements recommended during first trimester as the neural tube defect would coccur within the first 6 weeks before they know theyre pregnant, but 50% pregnancies unplanned – basis of recommendation for mandatory fortification
Pregnant women are expected to have supplements cos folate recommendation is so high
But pregnant women should avoid liver as a source as contains too much vit A as is dangerous to baby development
what is the Mean intake of folate in UK
220-330 µg/day
people have currently is 251 µg/day (women) and 344 µg/day (men)]
explain link between folate and cancer
Cancerous tissues like folate rich environments so is why we cant fortify all foods with folate
Folic acid don’t cause cancer but helps it grow if you do as the tumour can grow faster
explain folate absorption and metabolism
folate polyglutamates cleaved to monoglutamate
by brush border Zn-dependent peptidase deconjugase (takes polyglutimates off) in duodenum & jejunum (approx. 50% of food folate absorbed 85-100% oxidised folic acid)
then , alcohol deconjugase inhibitors in diet
then
methylated in intestinal mucosa & transported to liver in blood and bound to albumin in portal circulation reduced to DHF and then THF by DHFR in the liver
then
re-polyglutamated (polyglutimates reattached) & stored in liver (6-20mg stores; 2-7 months) or transported to other tissues
in absorption which of the 2 (Polyglutimates and Monoglutimates) can be absorbed
monoglutimates
explain folates interaction with alcohol
Alcohol is key thing that interferes with folate absorption
deficiency common in alcoholics
(60-70% binge drinkers are folate deficient)
intervention with alcohol (24g/day /2 weeks)
decreases blood folate by approx.10%
alcohol causes folate malabsorption
downsteam effect on key methyl donors
(e.g. SAM)
what cells are vulnerable to folate deficiency
rapid dividing cells as (requirement for DNA synthesis)
for a clinical deficiency how much folate is there in plasma and RBC - red blood cells
<2-3ng/ml in plasma and 100ng/ml in RBC
what does folate deficiency cause and look like
megaloblastic anaemia (cells enlarge) & large macrocytic red blood cells produced. - Giving someone folate with B12 deficiency will reduce megaloblastic anaemia occurring
Folate and B12 deficiency can mask each other
- this reduces O2 carrying capacity of blood – so causes anaemia
- loss of appetite (anorexia), sore mouth and inflamed tongue
- this causes depressed immunity, platelet and white blood cell division all reduce. So blood may not clot properly due to platelet reduction
nerve degeneration & dementia
drug induced (e.g. anti-epileptic drugs increase risk of neural tube defects) – making people more likey to folate deficiency
