Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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

We applied and evaluated 3 statistical approaches for the detection of heterozygotes for biotinidase deficiency in a randomly selected population of French adults. The first method, which used a cutoff value to dichotomize the population, lacked sensitivity. The second approach calculated the probability of heterozygosity for a given enzyme activity through the application of Bayes theorem to the normal density functions of the enzyme distributions of the obligate heterozygote and the test populations. A priori values of the means and standard deviations (SDs) of the genotypic distributions were used. This method was sufficiently sensitive for both population screening and genetic counseling, but requires prior knowledge of the frequency of the deficient gene (q). The third approach was similar to the second, however, maximum likelihood estimates of the means and SDs of the genotypic distributions were calculated and used to determine the probability of heterozygosity for a given enzyme activity. This method was as sensitive as the second method and is appropriate for screening populations for which there is little prior information about the gene frequency and the genotypic distributions. This method can also be used to estimate the gene frequency of the disorder within a given ethnic or racial population. Using this method, we estimated the frequency of heterozygotes (2pq) in the French population to be 0.012, which was similar to that estimated from the results of neonatal screening for biotinidase deficiency. These methods can be used to detect heterozygotes and to estimate the gene frequency of other inherited enzyme deficiencies.
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PMID:Statistical approaches for the detection of heterozygotes for biotinidase deficiency. 187 14

During a five-year-period (1985-1989) 420,000 newborns in Lower Saxony, FRG, were screened for biotinidase deficiency using biotinyl-para-amino-benzoic-acid as substrate. Three newborns with profound biotinidase deficiency (activity 1.1%, 2.1%, 2.3% of mean normal activity level) were detected. Nine newborns had partial biotinidase deficiency (activity 17-26% of mean normal activity level), thus giving an incidence of 1:140,000 with profound, and 1:46,667 with partial biotinidase deficiency, respectively. The infants with profound biotinidase deficiency are treated with biotin (2 x 5 mg/day) from the 3rd, 6th and 8th week of life and have developed normally so far. The children with partial biotinidase deficiency are not treated but followed up closely. The necessity of newborn screening for biotinidase deficiency is stressed.
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PMID:[Biotinidase deficiency. Results of neonatal screening 1985-1989 in Lower Saxony]. 189 47

Biotinidase activity was measured in plasmas of 1-, 7-, 14-, and 21-day-old rats from control dams and dams that had been fed a biotin-depleting diet from Day 15 of gestation. Biotinidase activity increased significantly in the plasma of rats from control and depleted mothers until Postnatal Day 14, after which there was a small but significant decline at Day 21. Differences between the mean activities of the two groups of pups on each sampling day were not significant and there were no significant differences in activity levels attributable to sex. Plasma albumin concentrations increased from birth until Day 21, and plasma biotinidase activity and albumin concentration were significantly correlated (r = +/- 0.43). We suggested that these two proteins may be controlled by a common mechanism in the early postnatal period, and that biotin deficiency does not affect the development of biotinidase activity. Because biotin-depleted neonatal pups show developmental changes in biotinidase activity similar to those of human newborns, and they can be produced reliably by depleting dams from Day 15 of gestation, they may be useful models for studying the developmental abnormalities associated with human biotinidase deficiency.
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PMID:Effects of age and biotin status on postnatal development of plasma biotinidase activity in rats. 201 13

Seventeen partially biotinidase-deficient patients detected by neonatal screening or family studies were compared with four patients with classical biotinidase deficiency. Using a sensitive HPLC method for biotinidase in plasma (substrate: biocytin) the patients could be divided into two groups: one with residual biotinidase activity, and the second with undetectable biotinidase activity (0-activity). Biocytin excretion, characteristically elevated in 0-activity patients, decreased rapidly with increasing residual biotinidase activity and was almost normal when residual activity exceeded 2-3% of mean normal. In one patient with classical disease (0-activity) biotin deficiency, typical organic aciduria and multiple carboxylase deficiency were found as early as at the second week of life. In contrast, 13 infants with residual activities from 1.2% to 23% had no remarkable clinical or biochemical abnormalities. However, in three 5-, 14- and 15-year-old healthy siblings with residual biotinidase activities between 2.3% and 4.2%, biotin deficiency was proven by decreased activities of the mitochondrial carboxylases in lymphocytes (30-57% of mean normal) and, in the older siblings, also by subnormal plasma biotin concentrations. In biotinidase deficiency, biotin depletion presumably occurs earlier in the brain than in other tissues and may thus first affect the central nervous system. For this reason and because of discrete biochemical abnormalities found in a patient with residual biotinidase activity of 8%, we suggest that at least all patients with residual activities below 10% should be treated with biotin.
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PMID:Comparison of patients with complete and partial biotinidase deficiency: biochemical studies. 210 51

Plasma biotin concentration and lymphocyte propionyl CoA carboxylase (PCC) and its activation index (the ratio of enzyme activity in cells incubated with biotin to activity in cells incubated without the vitamin) were compared as markers of biotin status in patients on biotin-free prolonged total parenteral nutrition (TPN). Five patients had been on biotin-free TPN for over 1 month when the study was started, and had already developed clinical signs that may be caused by this vitamin deficiency. They had markedly reduced levels of both biotin and carboxylase levels, which increased to near normal levels 4 months after biotin was added to the TPN. They initially presented subnormal plasma zinc concentrations which were normal at the end of the study. Another 4 patients also received biotin-free TPN. After 1 month propionyl CoA carboxylase, which was already below normal in 3 of them at admission, further decreased and became undetectable in 1 of them, who presented clinical deficiency manifestations. The enzyme activation index increased more than twice, although plasma biotin remained normal. When the vitamin was added to the TPN solution, PCC activity increased and its activation index decreased to normal. Plasma zinc concentrations remained normal throughout in this other group of patients indicating that changes of biotin markers are not likely to be related to zinc status variation. Plasma biotinidase, a key enzyme in biotin endogenous recycling, was already subnormal at admission and had become normal at the end of the study, but was not associated with the biotin status.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indicators of biotin status: a study of patients on prolonged total parenteral nutrition. 211 97

Pancreatic biotinidase activity was higher in hamster than in rat; these results were reversed in plasma. Uptake was studied in everted intestinal rings. Saturation kinetics at 37 degrees C were observed for biotin in hamster and for biocytin in rat, with a Vmax of 1.83 and 1.05 nmol min-1 ml-1 and an apparent Kt of 25.14 and 40.7 microM, respectively. Biotin uptake by hamster intestine was reduced at 4 degrees C and when choline or potassium replaced sodium; it was inhibited by biocytin only at very high concentrations. Biocytin uptake in the rat was small compared to passive diffusion and was not influenced by sodium or temperature; it was not inhibited by biotin. We observed only passive diffusion of biotin in rat and of biocytin in hamster. Our results suggest that protein-bound biotin may be absorbed mainly in its free form in the hamster. In the rat, on the other hand, at least part of the dietary biotin may be absorbed lysine-bound, as biocytin.
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PMID:Association of pancreatic biotinidase activity and intestinal uptake of biotin and biocytin in hamster and rat. 212 84

Holocarboxylase synthetase (HS) and biotinidase deficiencies have been identified as causes of biotin-responsive multiple carboxylase deficiency. Acetyl-CoA carboxylase (ACC) deficiency has been shown to occur in multiple carboxylase deficiency, and HS(-) fibroblasts are being employed to investigate compensatory regulatory responses in cells deficient in ACC. In previous studies, biotin starved HS(-) fibroblasts showed a reduced fatty acid content, an abnormal percentage composition of fatty acids, and a preservation of longer-chain fatty acid contents of cells. We herein ask whether the mutant cells show compensatory increases in the transport of longer-chain fatty acids from the medium into fibroblasts. In the present experiments there was no change in the uptake of arachidonate, palmitate or oleate following growth of mutant and control fibroblasts in (+) or (-) biotin conditions. Differential fatty acid uptake from the medium is therefore not a compensatory mechanism in HS(-) cells, and cannot account for the specific changes in fatty acid composition produced by biotin restriction.
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PMID:Fatty acid transport in multiple carboxylase deficiency fibroblasts. 212 77

Lipoamidase, as determined by lipoyl-p-aminobenzoic acid (L-pABA) hydrolyzing activity, and biotinidase in human serum have similar pH profiles, molecular weights, thermostabilities, and are similarly inhibited by p-hydroxymercuribenzoate and not inhibited by phenylmethylsulfonylfluoride. A monospecific polyclonal antibody prepared against biotinidase immunoprecipitated greater than 95% of serum L-pABA hydrolyzing activity and an identical proportion of biotinidase activity. In addition, children with profound biotinidase deficiency (less than 10% normal serum activity) have greatly reduced levels of L-pABA hydrolyzing activity in serum (less than 15% of mean normal activity) and obligate heterozygotes have activities intermediate between that of normal and profoundly deficient individuals. These results indicate that most, if not all, of the L-pABA hydrolyzing activity in human serum is due to biotinidase. Moreover, since the Km of L-pABA hydrolysis by serum is high, it is unlikely that lipoic acid is recycled in the serum by biotinidase.
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PMID:Lipoamidase activity in human serum is due to biotinidase. 222 62

Neonatal screening for profound biotinidase deficiency (less than 10% of the mean normal activity level) has identified a group of children with partial biotinidase deficiency (10% to 30% of mean normal activity). Because partial biotinidase deficiency may result in clinical consequences that may be prevented by treatment with biotin, we evaluated such individuals and their family members (1) to determine whether partial biotinidase deficiency is associated with symptoms and (2) to determine the inheritance pattern. We quantified serum biotinidase activity levels and obtained medical histories of probands, their parents and siblings, and additional family members. All children with partial deficiency were healthy at the time of diagnosis. One child, who was not initially treated with biotin, later developed hypotonia, hair loss, and skin rash, which resolved with biotin therapy. Four adults and three children with partial biotinidase deficiency were identified among family members of infants identified by neonatal screening. All these individuals were healthy, although one sibling had elevated urinary lactate excretion. A fifth adult with partial deficiency, found among clinically normal adult volunteers, later showed minor symptoms that resolved after biotin therapy. Like children with profound biotinidase deficiency, children with partial biotinidase deficiency are symptoms free at birth. However, the subsequent occurrence of symptoms of profound biotinidase deficiency in some persons with partial deficiency suggests that biotin therapy for this condition may be warranted.
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PMID:Partial biotinidase deficiency: clinical and biochemical features. 229 67


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