1/16
Why do B12 and folate deficiencies lead to HUGE red blood cells?

And, if the issue is DNA synthesis, why are red blood cells (which don't have DNA) the key cell line affected?

For answers, we'll have to go back a few billion years.

2/
RNA came first. Then, ~3-4 billion years ago, DNA emerged.

Among their differences:
🔹RNA contains uracil
🔹DNA contains thymine

But why does DNA contains thymine (T) instead of uracil (U)?

https://t.co/XlxT6cLLXg

3/
🔑Cytosine (C) can undergo spontaneous deamination to uracil (U).

In the RNA world, this meant that U could appear intensionally or unintentionally. This is clearly problematic. How can you repair RNA when you can't tell if something is an error?

https://t.co/bIZGviHBUc

4/
DNA's use of T instead of U means that spontaneous C → U deamination can be corrected without worry that an intentional U is being removed.

DNA requires greater stability than RNA so the transition to a thymine-based structure was beneficial.

https://t.co/bIZGviHBUc

5/
Let's return to megaloblastic anemia secondary to B12 or folate deficiency.

When either is severely deficient deoxythymidine monophosphate (dTMP*) production is hindered. With less dTMP, DNA synthesis is abnormal.

[*Note: thymine is the base in dTMP]

https://t.co/AnDUtKkbZh