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12 Cards in this Set

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Specify the one-carbon donors in metabolism and the groups they donate (SAM, THF, cobalamin)
Donors - Serine, glycine, histidine, formate and formaldehyde
CO2 is NOT a 1-carbon donor

Donated groups - methyl, formaldehyde, formic acid or carbonic acid.

Carriers - Tetrahydrofolate (THF) - primary
Methylcobalamin - based on vitamin B12
S-adenosylmethionine (SAM) - methylation reactions
Explain the formation of SAM and the reactions requiring SAM
Formation - ?

Reactions requiring SAM - methylation reactions
Norepenephrine → Epinephrine
Guanidoacetate → Creatine
Phosphotidylethanolamine → Phosphatidylcholine
Acetylserotinin → Melantonin
Nucleotides (DNA) → Methylated Nucleotides
Analyze the metabolism of monocysteine, vitamins/coenzymes required for metablism and interpret the clinical significance of homocysteine
Monocysteine metabolism ?
Vit required ?
Homocysteine - ?
Explain the formation of THF from folate and specify the mechanism of action of their inhibitors
Folate (inactive form) is reduced to Dihydrofolate and then reduced again to Tetrahydrofolate (active form).

Method of inhibition ?
Summarize the formation of one carbon group from amino acid metabolism and the utilization of 1-C groups for nucleotide synthesis
?
Indicate the different forms of THF (formyl, methylene and methyl) and reactions requiring the different forms of THF
A 1-carbon group can be carried and donated either as formyl (-CH=O), methylene (-CH2-) or methyl (-CH3)

Formyl THF and methylene THF are used as 1-C donors for synthesis of Purines & Pyrimidines

Methyl THF is only used in the converstion of Homocysteine to Methionine

Methyl THF is considered the storage form.
Identify the reactions requiring B12
1. Methylmalonyl CoA rearrangement to Succinyl CoA - needed to remove 3C products of fatty acid and amino acid metabolism by facilitating their transfer to TCA cyce

2. Remethylation of Homocysteine to Methionine - Sole method to release THF from methyl-THF. Stops Methyl-Trap
Compare and contrast the causes of folate and vitamin B12 deficiency
Folate defciency - caused by dietary lack, impaired absorption (intestine), increased requirement (pregnancy), antagonists (anti-cancer drugs)

Vitamin B12 deficiency - dietary lack, lack of IF, gastrectomy, increased demand (pregnancy)
Indicate the role of intrinsic factor in vitamin B12 absorption
1. B12 binds to IF in the duodenum
2. Transport to the ileum.
3. B12 associates with a carrier protein (Transcobalamin II)
4. Delivery to the liver.
Justify the mechanism of the occurrence of folate trap in B12 deficiency
If vitamin B12 is deficient, Tetrahydrofolate which has been methylated is trapped in that form as methionine synthase (homocysteine methyltransferase) is B12 dependent.
Compare and contrast the clinical and biochemical features of folate and vitamin B12 deficiency
Tetrahydrofolate (active form) requires Vit B12 (methy-cobalamin) to form during the methyl transfer to homocysteine in the creation of Methionine. It is derived from N5-methyl-tetrahydrofolate. Lack of B12 locks THF into methyl-THF

Lack of Tetrahydrofolate can be due to either a lack of folic acid OR vitamin B12. Folic acid and cobalamin are both prescribed in megaloblastic anemia.