6.1 BCHM - Biochem of Neuropathies Flashcards
rVitamin B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenate). are all involved in ________?
Vitamin B6 (pyridoxine), B7 (biotin), B9 (folic acid), B12 (cobalamins). are all invovled in _________?
First group = pure energy metabolism.
Second group = biosynthesis.
What causes neural tube defects in developing babies?
Not enough folic acid.
Where does folate come from naturally, how does this differ from the kind that the goverment puts in our foods?
Folates are acids found in green leafy veggies and in liver.
The government puts a folic acid in our foods which is a type of folate that is highly oxidized, plays no biological role, and very little is found in our body. However, it can be reduced to form biologically relevant folates.
Natural folates are reduced, why are these susceptible to random destruction by oxidation reactions? Why are folic acid supplements more stable?
Molecular oxygen readily accepts high energy reduced electrons and causes this destruction.
Supplements are already oxidized.
Folic acid dietary supplements contain folate which is more stable than natural reduced folates. In the liver the following conversion occurs.. Name the enzymes?
Folate binds dihydrofolate reductase.
This enzyme reduces folate -> dihydrofolate -> tetrahydrofolate.
Do the reduction reactions of folate require energy? What is the cofactor?
Reduction is occuring, therefore energy is in fact needed.
NADPH (biosynthetic energy molecule) powers this reaction.
How are reduced forms of folate retained in the cell? Think about the implications of lacking this substance.
Retained by linking several glutamate residues.
Tetrahydrofolate is converted into various folates that contain single carbon groups! These single carbon groups are important for donating __1___? ___2___ synthesis requires folates. Associate each form of folate with what it helps synthesize.
1) Donate one-carbon gropu to biosynthetic reactions.
2) DNA synthesis.
3) Formyl groups -> purines
methyl groups -> thymine bases
methionine -> S-adenosylmethioning (used in methylating histones)
Why does a deficiency in folate lead to spina bifida + anemia?
Neurons (in developing fetuses) and erythropoesis (in children/ adults) divide rapidly, rapidly dividing cells are especially sensitive to folate deficiency because they require DNA.
Check out the image below. How do 5-fluoruracil and methotrexate work as cancer therapeutics?
5-fluorouracil: mimics uracil, binds thymidylate synthase, inhibits production of thymine.
Methotrexate: mimics tetrahydrofolate binds to dihydrofolate reductase, and inhibits purine biosynthesis.
Basically they halt DNA synthesis.
Vitamin B12 is necessary for the regeneration of methionine. Methionine is used in the creation of SAM. Folates, SAM, B12 are at center of one carbon metabolism: they cycle 1 carbon units among themselves and undergo various cycles to donate carbon atoms to various biosynthetic pathways. What is the methyl-folate trap hypothesis?
B12 deficiency traps tetrahydrofolate in methyl form causing a functional folate deficiency.
SAM synthetase is only reaction in body that uses N5-methyltetrahydrofolate, B12 deficiency traps this form of folate => depletion of other forms of folate.
What is SAM (S-adenosylmethionine) role in the body?
Bodies most prevalent cofactor for donation of methyl groups in biosynthetic pathways.
Activates methyl groups by combing ATP w/ methionine.
Ex: donates methyl groups to convert: norepinephrin -> epinephrine. serotonin -> melatonin.
