I still don't quite understand the role of folate and B12... resources?

[bomgd3]

I must be somehow ******ed because I've looked at the diagrams in FA and UW again and again but I still don't quite understand the roles of folate and B12. Or really, the whole nucleic acid synthesis process. Can anyone help me, either by explaining or by recommending a resource? I never took biochem in undergrad and was an engineering major, so Lippincott's Biochem is too busy for me, although I've read it cover to cover.

Thanks in advance!

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[Convalaria]

I must be somehow ******ed because I've looked at the diagrams in FA and UW again and again but I still don't quite understand the roles of folate and B12. Or really, the whole nucleic acid synthesis process. Can anyone help me, either by explaining or by recommending a resource? I never took biochem in undergrad and was an engineering major, so Lippincott's Biochem is too busy for me, although I've read it cover to cover.

Thanks in advance!

Goljan RR, I understood all that pathway after his Anemia chapter

If you have enough time, I would recommend you to read and understand biochemistry first, then you will be able to understand much better all the rest

 

[Untraditional]

Goljan RR, I understood all that pathway after his Anemia chapter

👍

 

[iCY]

I must be somehow ******ed because I've looked at the diagrams in FA and UW again and again but I still don't quite understand the roles of folate and B12. Or really, the whole nucleic acid synthesis process. Can anyone help me, either by explaining or by recommending a resource? I never took biochem in undergrad and was an engineering major, so Lippincott's Biochem is too busy for me, although I've read it cover to cover.

Thanks in advance!

folate makes Tetra hydro folate (THF) which is a carbon donor. You need carbons to make nucleotides de novo (like for purine synth, you start with a ribose sugar & you add carbons till you make AMP or GMP...) so no folate = no carbons = can't make new nucleotides

Also note that theres a "strorage" form of folate called methyl-THF. B12 is necessary to regenerate the stored folate pool into the active folate pool so that the active folate pool can be used for nucleotide synthesis. This is why you can technically overcome the megaloblastic anemia of B12 def by supplementing folate (i.e., you're supplying fresh active folate so that you don't need to regenerate the stored folate pool)

its kind of a DUAL purpose pathway. Look @ that image. On the left side theres the little circular pathway where folate is being cycled around. Folate there is being used to make nucleotides. Now look @ the bigger circle on the right, the homocysteine/b12 are REGENERATING folate into the active folate form (tetrahydrofolate) & in the process converting methionine. This is a dual purpose pathway because the THF created can be used for nucleotides, whereas the methionine can be used to make S-adenosylmethionine (SAM) which can be used for methylating ****.

also make sure to understand what happens when you lose either B12 or folate. homocysteine will build up b/c it can't be converted to methionine, & methionine will be come an essential aminoacid b/c it can't be regenerated.

 

[ipizzy]

The only way I came to understand the folate/B12 and methionine/cystine pathways was by getting every single qbank question on these topics wrong. So in addition to RR path, do lots of questions, read the explanations, and eventually it will come together.

 

[Convalaria]

Plus to the role of Vit B12 in anemia: for example first it was problematic for me to understand how Vit B12 deficiency affects CNS (dorsal columns, spinocerebell. and corticospinal tracts) causing subacute degeneration. The answer is that Vit B12 also participates in reaction methylmalonyl CoA -> Succinyl CoA. If Vit.B12 is deficient, then there is accumulation of methylmalonyl CoA that is toxic for neurons and cause demyelination. This is why in treating of megaloblastic anemia it is important to distinguish whether it is due to folate or Vit B12 deficiency. One should prescribe both Vit. B12 and folates, since treating with folate only can improve anemia by increasing reticulocyte count. But if this anemia is due to Vit B12 deficiency and you don't supplement with Vit B12 you may lose time and not correct neurologic disease.

Edit: pathway attached

 

[bomgd3]

Thanks guys! Goljan RR Path has helped, and I'm looking at his biochem book right now.

Another more specific question: all of my books say that folate deficiency impairs synthesis of thymine AND purines. Yet, when I look at these pathways, I don't see anywhere that folate factors into purine synthesis. Thoughts? Is this because of the various regulatory mechanisms that keep nucleotide synthesis around equal?

 

[iCY]

Thanks guys! Goljan RR Path has helped, and I'm looking at his biochem book right now.

Another more specific question: all of my books say that folate deficiency impairs synthesis of thymine AND purines. Yet, when I look at these pathways, I don't see anywhere that folate factors into purine synthesis. Thoughts?

not important for you to know/waste time learning.

 

[beeitchness]

Thanks guys! Goljan RR Path has helped, and I'm looking at his biochem book right now.

Another more specific question: all of my books say that folate deficiency impairs synthesis of thymine AND purines. Yet, when I look at these pathways, I don't see anywhere that folate factors into purine synthesis. Thoughts? Is this because of the various regulatory mechanisms that keep nucleotide synthesis around equal?

Folate is involved in specific reactions leading to formation of IMP from PRPP, in de novo purine synthesis. You don't need to know those specific reactions.