Biotin is an essential element in humans required as a prosthetic group for carboxylase enzymes such as acetyl-CoA carboxylase I and II, pyruvate carboxylase, methylcrotonyl-CoA carboxylase and proprionyl-CoA carboxylase. Deficiency of biotin results in hallucinations, depression, muscle pain localised paresthaesia and dermatitis. However, it is increasingly being realised amongst nutritionists that marginal biotin deficiency (insufficiency) is much more common that was once thought. A useful marker of biotin insufficiency may be 3-hydroxyisovaleryl carnitine. As activity of methylcrotonyl CoA carboxylase is reduced, the catalysis of an essential step in the mitochondrial catabolism of the branched chain amino acid leucine is impaired, which causes accumulation of its substrate 3-methylcrotonyl-CoA. This is then metabolised via another pathway to form 3-hydroxyisovaleryl carnitine, which is transported across the mitochondrial membrane where it eventually appears in plasma and urine.
To investigate the usefulness of 3-methylcrotonyl-CoA as a marker for marginal biotin deficiency, researchers1 induced marginal biotin deficiency in 10 healthy adults. Biotin deficiency was accomplished by having the subjects consume undenatured egg white for 28 days. Egg white contains a protein called avadin that is able to covalently bind to biotin with high affinity and specificity and thus decreases absorption. Following the 28 day depletion phase, subjects had their biotin status repleted by removal of the egg white and the addition of a 30 µg biotin supplement to the normal mixed diet. The results showed that marginal biotin depletion caused an increase in plasma concentrations of 3-hydroxyisovaleryl carnitine, an effect that was reversed upon repletion with supplements. This suggests that 3-hydroxyisovaleryl carnitine is an effective plasma marker of biotin status which is easy to collect, stable, and only requires a small sample volume.
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