Absorption, transport and metabolism of biotin Domina Petric, MD

Absorption of biotin I.

Liberation from bound forms In the digestion of food proteins, protein-bound biotin is released by the hydrolytic action of the intestinal proteases to yield the ε-N1-biotinyllysine adduct, biocytin, from which free biotin is liberated by the action of an intestinal biotin amide aminohydrolase, biotinidase.

Free biotin is absorbed in the proximal small intestine by what appears to be two mechanisms, depending on its lumenal concentration.

Facilitated transport At low concentrations, biotin is absorbed by a saturable, facilitated mechanism dependent on Na+. This process has been found to be inhibited by certain anticonvulsant drugs and chronic ethanol exposure. The inhibitory effect of ethanol has been demonstrated with solutions as dilute as 1% (v/v).

Facilitated transport Similar inhibition has been demonstrated for ethanol against biotin transport in human placental basolateral membrane vesicles, which also occurs by an Na+-dependent, carrier-mediated process.

Passive diffusion At high lumenal concentrations, free biotin is also absorbed by nonsaturable, simple diffusion.

Transport of biotin II.

Unbound biotin Less than half of the total biotin present in plasma appears to be free biotin, the balance being composed of bisnorbiotin, biotin sulfoxide and other metabolites. Only 12% of the total biotin in human plasma is covalently bound.

Cellular uptake

Sodium-dependent vitamin transporter (SMVT) A Na+-dependent, carrier-mediated process that is not specific for the vitamin, but that functions in the cellular uptake of biotin, pantothenic acid and lipoic acid with similar affinities. Biotin uptake by intestinal cells is inhibited by the activation of protein kinase C, apparently through phosphorylation of SMVT.

Monocarboxylate transporter That this member of the monocarboxylate tansporter family can facilitate the cellular uptake of biotin into peripheral blood mononuclear cells explained the facts that biotin is taken up by those cells by process with a Km three orders of magnitude less than that for SMVT-mediated transport, and is not competitively inhibited by either pantothenic or lipoic acids.

Tissue distribution Appreciable storage of the vitamin appears to occur in the liver: 800-3000 ng/g. Most of this appears to be in mitochondrial acetyl CoA carboxylase. Hepatic stores appear to be poorly mobilized during biotin deprivation and do not show the reductions measurable in plasma under such conditions.

Metabolism of biotin III.

Linkage to apoenzymes Free biotin is attached to its apoenzymes via the formation of an amide linkage to the ε-amino group of a specific lysine residue. In each of the four biotin dependent enzymes, this binding occurs in a region containing the same amino acid sequence: -Ala-Met-biotinyl-Lys-Met-. It is catalyzed by biotin holoenzyme synthetase.

Biotinidase is the major biotin-binding protein in plasma. Recycling the vitamin The normal turnover of the biotin-containing holocarboxylases involves their degradation to yield biocytin. The biotinyl lysine bond is not hydrolyzed by cellular proteases-it is cleaved by biotinidase to yield free biotin. Biotinidase is the major biotin-binding protein in plasma. It is also present in breast milk, in which its activity is particularly high in colostrum.

Recycling the vitamin The proteolytic liberation of biotin from its bound forms is essential for the reutilization of the vitamin, which is accomplished by its reincorporation into another holoenzyme. Congenital deficiencies of biotinidase are characterized by deficiencies of the multiple biotin-dependent carboxylases. In some cases, they can be corrected with pharmacologic doses of the vitamin.

Catabolism A small fraction of biotin is oxidized to biotin D- and L-sulfoxides, but the ureido ring system is not otherwise degraded. The side chain of a larger portion is metabolized via mitochondrial β-oxidation to yield bisnorbiotin and its degradation products. Biotin catabolism appears to be greater in smokers than in nonsmokers.

Excretion Biotin is rapidly excreted in the urine. Half of urinary biotin occurs as free biotin, other half is composed of bisnorbiotin, bisnorbiotin methyl ketone, biotin sulfone, tetranorbiotin-L-sulfoxide and various side-chain products. Unabsorbed biotin appears in the feces. Only a small amount (<2% of an intravenous dose) of biotin is excreted in the bile.

Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.