Biotin is synthesized by microorganisms in the gut. Supposedly no one has a deficiency of biotin. I have been arguing that the the sodium-dependent multivitamin transporter (SMVT) which transports biotin is dysregulated.
Given a biotin deficiency the difficulty should be very easy to fix. Biotin is a widely marketed supplement. The RDA for biotin is 30 micrograms per day. Biotin is very frequently sold in 5000 and 10,000 supplemental forms. Taking one of the biotin tablets daily should fix everything. But I do not think this is the case. Fixing a biotin deficiency that has gone on a long time is not easy to fix at all. .
There are five biotin dependent enzymes methylcrotonyl CoA carboxylase which is involved degradation of branched-chain amino acids, propionyl-CoA carboxylase which is also involved in degradation of branched-chain amino acids, acetyl-CoA carboxylase alpha and acetyl-CoA carboxylase beta both of which are involved in the synthesis of fatty acids and pyruvate carboxylase.
The difficulty that arises is that with long term deficiencies of biotin due to dysregulation of the SMVT is that genes for biotin-dependent enzymes can become hypermethylated,. Supplementing with biotin alone no longer fixes the difficulty. A difficulty that should be dirt simple to fix, just go to the grocery store purchase some biotin and take one tablet a day, is no longer easy to fix. The SMVT besides transporting biotin also transports pantothenic acid. Pantothenic acid would have to be supplemented. Branched-chain amino acids would also have to be supplemented. With acetyl-CoA carboxylase, which is a biotin dependent enzyme, hypermethylated long chain saturated fatty acids have to be supplemented.
But the difficulties are even more extreme. Histones at the SMVT locus can become biotinylated which reduces transport by the SMVT. Supplementing with biotin could reduce transport of pantothenic acid by the SMVT via biotinylation of histones at the SMVT locus. How long does biotinylation last? I don’t know. The SMVT also transports iodide. Supplementing with biotin could reduce transport of iodide resulting in hard to diagnose thyroid difficultise. I think a lot of individuals could have difficulties with biotin and the difficulties are not easy to fix.