Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
40 Cards in this Set
- Front
- Back
1C metabolism definition
|
Processes that move 1C via methylene/methyl/formyl
|
|
1C metabolism vitamins
|
- Folate compounds (carry the C)
- Vitamin B12 |
|
Folic acid sources
|
"Foliage" - green, leafy vegetables
|
|
Folate not used directly
|
Two separate reductions via dihydrofolate reductase (DHFR)
Folate -> DHF -> THF |
|
DHFR reaction
|
Folate + NADPH + H+ (via DHFR) -> DHF
- 2H added each rxn |
|
Methotrexate
|
Cancer drug, inhibits Folate -> THF reactions
- Slows DNA synthesis, bad for quickly dividing cells |
|
1C binding site
|
on the N5 or N10 atoms
|
|
Main C-carrying forms of folate
|
N5-methyl THF (methyl on N5)
- N5,N10-methylene THF (CH2 shared by N5 and N10) |
|
Major carbon donor
|
Serine - donates methyl
- Not essential acid - never rate limiting.. |
|
Serine C-donating rxn enzyme
|
Serine hydroxymethyl transferase
|
|
Serine C-donating rxn
|
Serine + THF (via Serine hydroxymethyl transferase) -> Glycine + N5,N10 methylene THF + H2O
|
|
Absortion of dietary folate
|
Naturally polyglutamated
- Glutamates removed by small intestine enzyme - Transported into small intestine cell by reduced folate carrier - Reduced by DHFR - Converted to N5-methyl THF - Transported in blood, taken up by cells - Glutamate tail added once in cell - traps it |
|
1C-THF functions
|
1) dUMP -> dTMP (Thymidylate synthase rxn)
2) Purine nucleotide synthesis 3) Methionine cycle |
|
Thymidylate synthase rxn
|
dUMP + 5,10-Methylene THF (via Thymidylate synthase) -> dTMP + DHF
|
|
Thymidylate synthase rxn is weird b/c...
|
N5,10-methylene THF provides C and reducing equivalents
|
|
Methionine cycle purpose
|
Burn one ATP to create SAMe, a high-energy C-donating molecule
|
|
SAMe purpose
|
Besides THF variants, does almost ALL other 1C transfers
|
|
SAMe synthesis
|
Methionine + ATP (via methionine adenosyl transferase) -> SAMe + PPi + Pi
|
|
Methionine cycle rxns
|
Methionine + ATP -> SAMe + PPi + Pi
SAMe + something -> S-adenosyl homocysteine + methylated something S-adenosyl homocysteine + H2O -> Adenosine + Homocysteine Homocysteine + B12 + N5-methyl THF -> Methionine + THF |
|
B12 deficiency
|
THF gets "trapped" as N5-CH3-THF
- methionine not regenerated |
|
Alternate homocysteine destiny
|
Can become cysteine instead of regenerating methionine
|
|
B12 sources
|
Only synthesized by microorganisms - get from animal sources (liver, mollusks)
- No B12 in purely vegetarian diet! |
|
B12 malabsorption
|
Some kind of GI disease/problem
|
|
B12 absorption process
|
B12 bound to R-proteins at ingestion
Intrinsic factors (IF) released in stomach Pancreatic proteases remove R-proteins IF binds B12 in duodenum IF-B12 absorbed in ileum Inside lumenal cell, IF removed, transcobalamine II (TCII) gets B12 TCII-B12 taken up by cells via TCII receptors |
|
Atrophic gastritis
|
Autoimmune disease, parietal cells destroyed
- No stomach acid, no B12 absorption either - Can lead to pernicious anemia... |
|
Tapeworm
|
also competes for B12 uptake
|
|
Other B12-dependent process
|
Propionyl CoA (from odd # FA) -> Succinynl CoA
|
|
Elderly nutrition
|
Often marginal B12 shortages in nursing homes, etc.
|
|
High plasma N5-CH3-THF
|
B12 deficiency
|
|
Low plasma B12
|
B12 intake deficiency
|
|
Elevated plasma homocysteine
|
THF and/or B12 deficiency
|
|
Folate deficiency
|
Low serum folate, low red cell folate, normal B12
|
|
B12 deficiency
|
High serum folate, low RBC folate, low B12, high methylmalonate
|
|
Folate deficiency pathophysiology
|
Failure of purine/thymidylate synthesis
- Slowed DNA synthesis in marrow, Hb production normal - Large RBC's - more Hb than normal inside |
|
Macrocytic anemia
|
Large RBC's in circulation, lyse
|
|
Megaloblastic anemia
|
Cells in marrow have large nuclei, poorly condensed chromatin
- DNA synthesis not keeping up with Hb production |
|
B12 deficiency pathophysiology
|
Folate trapped as N5-CH3-THF
- Functional shortage of folate - Impaired DNA synthesis, low platelets, low WBC - Neurological problems |
|
Pernicious anemia
|
Degeneration of spinal cord, nervous system
- Dementia, other irreversible damage - B12 supplements can stop damage, can't reverse it |
|
Neural tube defects
|
Prenatal defect due to lack of folate
|
|
Elevated homocysteine levels
|
Result from lack of folate, B12
- Toxic to endothelium - increased heart attack, stroke - Vitamin supplements reduce levels, don't reverse damage |