Vitamin B9 - Folate Flashcards
List dietary sources of folate
Green vegetables, mushrooms, legumes
Fruits: strawberries and oranges
Liver
Fortified grains
Discuss the digestion of folate
Polyglutamate forms must first be hydrolyzed into monoglutamate forms by conjugases
Conjugases
- present in pancreatic juices and bile
- zinc dependent enzymes
- inhibited by conjugase inhibitors in certain foods and chronic alcohol consumption
- not needed for Folic acid, as it is already a monoglutamate
Discuss the absorption of folate
Absorbed throughout the small intestine, but most effeciently in the jejunum
3 mechanisms of absorption
- Folate binding proteins
- saturable
- dependent on pH, ATP & Na+ - Reduced folate transporter
- transports 5-methyl THF - Diffusion
- especially at high doses
Discuss the transport of folate
Folate is reduced to tetrahydrofolate (THF) in the enterocyte
Then methylated to 5-methyl THF to be transported in portal circulation
Transport across basolateral membrane and into the liver and other tissues is mostly carrier dependent although diffusion does occur in some tissues as well
Discuss storage of folate
Glutamate residues are added to the monoglutamate folate
- allows for production of various coenzymes
- serves to trap the folate inside the cell
Liver stores ~50% of folate in the body
Describe the function and mechanism of action of folate
Coenzyme function (THF):
Accepts methyl groups and serves as a donor of methyl groups
Needed to make other active forms of folate
Amino acid metabolism
- remethylation of homocysteine to make methionine (B12 also needed)
- conversion of phenylalanine to tyrosine
Other functions: Formation of heme group into hemoglobin Formation of choline into ethanolamine Conversion of niacin to N-methylnicotinamide (for excretion) Purine & pyrimidine synthesis - folate essential for cell division
Describe the metabolism and excretion of folate
Excreted in urine and feces
- any excess in urine
- ~100 mcg/d is secreted by liver into bile and almost all of that is reabsorbed
Describe consequences and symptoms of deficiency of folate
Increased risk of neural tube defects during fetal development
Megaloblastic macrocytic anemia
- abnormal DNA synthesis and failure of RBCs to divide
- continued synthesis of RNA, excess production of cytoplasmic constituents
Symptoms
- weakness and fatigue
- headaches
- SOB, palpitations
- depression, anxiety, irritability, difficulty concentrating, confusion, dementia
- angular cheilosis, glossitis
- neuropathy
- impaired immune function
Who is at most risk of folate deficiency?
Pregnant women Alcoholics Genetic polymorphism MTHFR677C-T (5-15% of North Americans) H. Pylori infection People taking certain medications - OCP - methotrexate - binds to dihydrofolate reductase and prevents THF synthesis People taking high doses of B6 or B12
Describe consequences and symptoms of toxicity of folate
UL - 1 mg synthetic Folic acid
Doses of 15 mg/d can cause insomnia, malaise, irritability, GI distress (*however, doses of up to 80 mg/d have been given without adverse effects)
Rare anaphylactic reactions
Folic acid supplementation can mask lab diagnosis of vitamin B12 deficiency and may increase requirements for B12
Describe the assessment of nutrient status of folate
Serum folate - but it reflects recent dietary intake
RBC folate
-more reflective of folate in tissues (represents vitamin status when RBC was formed, 2-3 months prior)
- decreased with B12 deficiency and increased with iron deficiency
When is folate contraindicated?
I patients receiving methotrexate as a antineoplastic drug and other anticancer drugs.
Discuss some of the therapeutic uses (clinical indications) of folate
Prevention of neural tube defects - can prevent 75% of NTD
Megaloblastic macrocytic anemia
Atherosclerosis
- due to ability to reduce elevated homocysteine
