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Lymphocyte propionyl-CoA carboxylase and its activation by biotin are sensitive indicators of marginal biotin deficiency in humans ^1,2,3

¹ From the Departments of Biochemistry and Molecular Biology (SLS, AB, MMM, DMM, and NIM) and of Pediatrics (DMM), University of Arkansas for Medical Sciences, Little Rock, AR, and the General Clinical Research Center of the University of Arkansas for Medical Sciences, John L McClellan Veterans Hospital, Little Rock, AR (AW and DMM)

Background: Marginal biotin deficiency may be a human teratogen. A biotin status indicator that is not dependent on renal function may be useful in studies of biotin status during pregnancy. A previous study of experimental biotin deficiency suggested that propionyl-coenzyme A carboxylase (PCC) activity in peripheral blood lymphocytes (PBLs) is a sensitive indicator of biotin status.

Objective: We examined the utility of measuring PCC activity and the activation of PCC by biotin in detecting marginal biotin deficiency.

Design: Marginal biotin deficiency was induced in 7 adults (3 women) by egg-white feeding for 28 d. Blood and urine were obtained on days 0, 14, and 28 (depletion phase) and 44 and 65 (repletion phase). PBLs were incubated with (activated) or without (control) biotin before PCC assay. The activation coefficient of PCC is the ratio of PCC activity in activated PBLs to that in control PBLs. The significance of differences for all measurements was tested by repeated-measures analysis of variance with Fisher's post hoc test and Bonferroni correction.

Results: Changes in the urinary excretion of biotin and of 3-hydroxyisovaleric acid confirmed that marginal biotin deficiency was successfully induced. By day 14, PCC activity had decreased (P < 0.0001) to below the lower limit of normal in all subjects. By day 28, the activation coefficient of PCC had increased significantly (P = 0.003) and was above the upper limit of normal in 6 of 7 subjects.

Conclusion: PCC activity is the most sensitive indicator of biotin status tested to date. In future pregnancy studies, the use of lymphocyte PCC activity data should prove valuable in the assessment of biotin status.

Key Words: Biotin • biotin deficiency • humans • lymphocytes • propionyl-CoA carboxylase • activation coefficient

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