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Xaa 20 is Leu, Lys, or Met

A study conducted in 2016 thus came to the following conclusion: If we had restricted the treatment of symptomatic patients to patients with both low serum levels and elevated metabolite levels, 63% of patients who responded well to the therapy would not have received treatment [] Only 16% of patients with good clinical improvement from vitamin B12 therapy had low serum levels and 54% of patients with good clinical improvement from vitamin B12 therapy had serum levels higher than 300 pg/mL. Some experts thus advise high-dose B12 treatment to treat all known nervous symptoms associated with B12 deficiency

This may contribute to the prolonged perception of pain

1c), as excessive membrane affinity hinders efficient transmembrane passage to reach intracellular targets, directly impairing degradation activity even when the warhead is optimized