Progress 10/01/00 to 10/01/01
Outputs
The current CRIS project on the interaction between biotin nutriture and immune function depends upon appropriate animal models. Studies were undertaken to analyze the relationship between dietary biotin intake and biotin metabolism in rats. Biotin status of rats was manipulated through dietary intervention to model moderate biotin deficiency, adequacy, supplementation, and pharmacological biotin supplementation (0, 0.06, 0.6, and 100 mg/kg, respectively). Urinary biotin excretion was directly related to biotin intake, but no difference between biotin adequate and supplemented rats was detected. In contrast, plasma biotin was directly and significantly regulated by biotin intake at every intake level. A hepatic free biotin pool was directly demonstrated in these studies, and like plasma, its size was directly related to dietary biotin intake. The relationship between dietary biotin intake and protein bound biotin was also analyzed. Moderate biotin deficiency markedly
decreased the abundance of each biotinylated polypeptide in rat liver. Biotin supplementation did not significantly elevate the abundance of biotinylated pyruvate, propionyl CoA, methylcrotonyl CoA, or acetyl CoA carboxylase 1. The abundance of biotinylated acetyl CoA carboxylase 2, however, was significantly higher in biotin supplemented rats. Pharmacological biotin intake significantly reduced the abundance of biotinylated propionyl CoA and methylcrotonyl CoA carboxylase. These results indicate that (i) moderate biotin deficiency reduces free and protein bound biotin, (ii) biotin intakes in rats that mimic the currently recommended daily value (DV) do not result in full protein biotinylation, and (iii) pharmacological supplementation may reduce the abundance of functional carboxylases. Overall, these studies suggest that the lack of outward appearances may not be a reliable method by which to assess biotin status in the general population. Glucocorticoid administration is a common
method to treat chronic disease states, including inflammatory conditions. The effect of dexamethasone on biotin metabolism was analyzed in rats consuming a purified diet containing a more physiological level of dietary biotin intake (0.06 mg/kg). Acute (5 h) dexamethasone administration (0.5 mg/kg) elicited elevated urinary glucose output as well as elevated urinary biotin excretion and serum biotin. Renal and hepatic free biotin was also significantly elevated by acute dexamethasone administration. Chow fed rats treated with an acute administration of dexamethasone demonstrated significantly elevated urinary glucose excretion, urinary biotin excretion, and serum biotin, but no change in tissue associated biotin was detected. Chronic administration of dexamethasone (0.5 mg/kg i.p.) over four days significantly elevated urinary glucose excretion 42%, but had no effect on urinary biotin excretion, serum biotin, or hepatic or renal associated free biotin. These results demonstrate the
existence of novel regulatory pathways for biotin metabolism and the possibility that experimental models with high initial biotin status may mask potentially important regulatory mechanisms.
Impacts
Initial studies into the relationship between biotin nutriture and immunity have demonstrated a significant role for this vitamin in the inflammatory response. Both the metabolism and function of biotin during inflammation appear to be altered, but the mechanisms behind these alterations are as yet unclear. These results are expected to aid in the administration of essential nutrients to the critically ill to reduce morbidity and enhance recovery.
Publications
- Rathman, S, McMahon, R. (2001) "Acute, but not chronic, dexamethasone administration increases urinary biotin excretion and plasma biotin in rats". American Journal of Physiology: Endocrinology and Metabolism (in press).
- Lewis, B.J., Rathman, S., McMahon, R.J. (2001). "Dietary biotin intake modulates the free and protein bound biotin pool in rat liver" The Journal of Nutrition. 273(3): 859-864.
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