Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.12 (biotinidase)
 392 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biotin uptake, utilization, and efflux were studied in normal and biotin-deficient cultured rat hepatocytes. Biotin-deficient cells accumulate about 16-fold more biotin than do normal cells when incubated with a physiological concentration of biotin for 24 h. This difference is due to the greater amount of protein-bound biotin relative to free biotin in biotin-deficient hepatocytes, and is attributable to the presence of more apocarboxylases in deficient cells. The rate of biotin uptake and the rate of activation of the carboxylases, acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and beta-methylcrotonyl-CoA carboxylase, are proportional to the concentration of exogenous biotin. Increases in carboxylase activities are proportional to the concentration of biotin only at exogenous biotin concentrations of less than 410 nM. Concentrations of 410 nM or more biotin increase carboxylase activities to normal or near normal. Biocytin inhibits biotin uptake at very high concentrations, whereas desthiobiotin and lipoic acid have no effect. Biocytin in the medium results in carboxylase activation either intracellularly or extracellularly by conversion to biotin by biotinidase. Investigation of the efflux of biotin from normal and biotin-deficient cells preincubated with the vitamin showed greater retention of biotin by biotin-deficient cells than by normal cells over 24 h. Retention of free biotin is similar in biotin-deficient and normal cells. The greater amount of biotin retained by biotin-deficient cells is accounted for by the greater amount of bound biotin in these cells. These results suggest that the free and bound biotin pools are independently regulated. The ready loss of free biotin from these cells has implications for the treatment of inherited, biotin-responsive carboxylase deficiencies.
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PMID:Biotin uptake, utilization, and efflux in normal and biotin-deficient rat hepatocytes. 179 12

In evaluating potential indicators of biotin status, we quantitated the expression of biotin-related genes in leukocytes from human blood of normal subjects before and after inducing marginal biotin deficiency. Biotin deficiency was induced experimentally by feeding an egg-white diet for 28 d. Gene expression was quantitated for the following biotin-related proteins: methylcrotonyl-CoA carboxylase chains A (MCCA) and B (MCCB); propionyl-CoA carboxylase chains A (PCCA) and B (PCCB); pyruvate carboxylase (PC); acetyl-CoA carboxylase isoforms A (ACCA) and B (ACCB); holocarboxylase synthetase (HCS); biotinidase; and 2 potential biotin transporters: sodium-dependent multivitamin transporter (SMVT) and solute carrier family 19 member 3 (SLC19A3). For 7 subjects who successfully completed the study, the abundance of the specific mRNAs was determined by quantitative real-time RT-PCR at d 0 and 28. At d 28, SLC19A3 expression had decreased to 33% of d 0 (P < 0.02 by two-tailed, paired t test). Expression of MCCA, PCCA, PC, ACCA, ACCB, HCS, biotinidase, and SMVT decreased to approximately 80% of d 0 (P < 0.05). Expression of the MCCB and PCCB chains that do not carry the biotin-binding motif did not change significantly; we speculate that expression of the biotin-binding chains of biotin-dependent carboxylases is more responsive to biotin status changes. These data provide evidence that expression of SLC19A3 is a relatively sensitive indicator of marginal biotin deficiency.
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PMID:Biotin deficiency reduces expression of SLC19A3, a potential biotin transporter, in leukocytes from human blood. 1562 30