1 · Biotin covalently anchors to a Lys
Biotin cannot catalyze on its own until HCS bonds it to a specific lysine on an enzyme, where it becomes a swing arm, and humans have only 5 such enzymes.Vitamin B7 (biotin) is a sulfur-containing bicyclic small molecule — present in food as free biotin or protein-bound form (liver, egg yolks, nuts, yeast, mushrooms).After absorption, biotin enters the cell — but on its own it has no catalytic activity. To work, it must be covalently attached to a specific Lys (lysine) residue of an enzyme, forming a 'holo-enzyme'.
The attaching enzyme: HCS (holocarboxylase synthetase) — forms an amide bond between biotin's carboxyl group and the ε-amino group of Lys, using one for energy.
Key structure: biotin is tethered to the enzyme via this covalent bond, but its two terminal rings act like a 'swing arm', capable of swinging ~ 1.4 nm between two active sites — this is how it works.
There are only 5 biotin-dependent enzymes in humans:
· ACC1 / ACC2 (acetyl-CoA carboxylase) — switch for fatty-acid synthesis
· PC (pyruvate carboxylase) — gluconeogenesis + anaplerosis
· PCC (propionyl-CoA carboxylase) — odd-chain fatty acids + Val/Ile/Met/Thr catabolism
· MCC (3-methylcrotonyl-CoA carboxylase) — Leu catabolism.
All 5 are 'carboxylases' — their common action is 'grab a CO₂ + tether it onto the substrate'.