Metabolic alterations of free and protein-bound biotin in rats during dietary biotin manipulation and endotoxin exposure

The water-soluble B-vitamin biotin is an essential cofactor for the biotin-dependent carboxylases involved in the metabolism of carbohydrate, protein, and fatty acids. Although a frank biotin deficiency is thought to be rare, more recent evidence suggests that a marginal biotin deficiency may be more prevalent than previously appreciated. Despite substantial advances in molecular and analytical techniques, the biotin requirement of healthy and physiologically stressed animals remains poorly understood.; To address these gaps in the understanding of biotin nutriture, the effect of dietary biotin intake on plasma, urine, and tissue levels of free and protein-bound biotin was examined. Rats were fed an egg-white based AIN 76A diet containing 0, 0.06, 0.6, or 100 mg biotin/kg diet for three weeks. Indicators of biotin status (urinary biotin excretion, liver free biotin, and liver protein-bound biotin) in rats fed a diet supplemented to 0.06 mg biotin/kg diet were equal to that of rats fed a 0.6 mg biotin/kg diet, a level used in previous studies indicating adequate biotin status. This study also demonstrated that distinct differences in these pools occurred as early as 3 weeks on a biotin-deficient diet with no outward signs of biotin deficiency, thus potentially modeling a marginal biotin deficiency in humans.; To determine the changes in biotin metabolism during an acute inflammatory response, bacterial lipopolysaccharide (endotoxin) was administered to biotin-adequate (0.06 mg biotin/kg diet) and biotin-deficient rats (0 mg biotin/kg diet). Endotoxin administration modulated both free and protein-bound biotin pools in adequate rats. Free biotin increased in the serum and liver. Protein bound biotin, represented by the relative abundance of biotinylated carboxylases, also changed; however, increases or decreases were specific for the individual carboxylases. Of note, a novel biotinylated protein with an apparent molecular weight of 61 kDa appeared in endotoxin treated animals. These changes provide plausible mechanisms to account for the observed changes in carbohydrate, protein, and fatty acid metabolism associated with acute inflammation. Biotin deficiency prior to endotoxin challenge delayed or lessened the changes in carboxylase metabolism seen in adequate rats and may indicate a reduced ability to respond to acute inflammation.