Nutrition 2: Folic acid, TFR Flashcards
What are the 3 major structural components of Folates (Vit b9). Which part carries the single carbon group
- Bicyclic, heterocyclic pteridine ring (double ring)–> carries the single carbon group
- p-amino benzoic acid (one hex)
- glutamic acid (chain)
How is Folic acid changed to active form in the human, what catalyses this reaction
Once inside the cell folic acid is converted to active form Tetrahydrofolate by two separate donations of NADPH giving 2 Hs.
Both reactions Catalysed by dihydrofolate reductase.
What modification to the structure of folic acid is done in the liver
Addition of more glutamic acid residues in liver cells make a poly-y-glutamate tail to help with storage
Where does folate and Tetrahydroxyfolate derivatives come from in diet and how is it absorbed
Bacteria, yeast, higher plants make polyglutamate form of folic acid
When digested,
Humans intenstinal cells convert polyglutamate to monoglutamate which is able to be absorbed by active transport.
After conversion to active form by intestinal cells, where is THF is stored and how
50% of THF is stored in the liver by converting to non transportable form -polyglutamate. This form also has higher affinity for enzymes.
What are the type of single carbon functional groups transferred by Folates B9 and what position does it transfer it to
It transfers single carbon groups: methyl, methylene (CH2) and formyl (HCO)
to the THF intermediates at positions 5 and 10
What are the sources of single carbon functional groups transferred by folates and what are the major products
Sources: Serine, Histidine and Glycine + formate
Products: Methionine (amino acid), dTMP, Purines (dna/rna synthesis) and formylmethionyl tRNA (bacteria/mitochondria protein synthesis)
Why are folates essential for growth
Major products from pathways involving THF are essential for Amino acid synthesis, Purine synthesis and monophosphate synthesis
What is an antimetabolite and how does it lead to drug development
A synthetic compound usually structurally related to a metabolite that inhibits an enzyme by binding.
This can be used in anticancer, antibacterial and antiparasitic drugs to inhibit those specific enzymes.
What is a Neural tube defect and what are the two types of NTD
Neural tube defect is the failure of neural tube to close
Cranial end: Anencephaly where the cerebral cortex fails to develop which leads to death immediately
Caudal end:
Spina bifida where the spinal cord develops abnormally and causes paralysis of lower extremities, imparing bowel and bladder function
How does folate prevent NTDS (methylation hypothesis)
Folate prevents NTDs by increasing methylation of various molecules that are essential to cellular processes.
Decreased methylation of proteins, lipids and metabolites can lead to altered gene expressions/protein function which leads to NTD
How is macrocytic anaemia linked to deficiency of folates
Red blood cells were unable to replicate DNA quick enough before dividing due to lack of folates so get very large RBCs
Give an example of a microorganism antimetabolite
Sulfonamides which inhibits the synthesis of folic acid by inhibiting bacterial Dihydropteroate synthetase
Give an example of a human antimetabolite
Mathotrexate which inhibits Dihydrofolate reductase stopping the conversion to active form of folate
