Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.4.1.1 (pyruvate carboxylase)
 1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biotin-dependent enzymes are involved in carboxylation, decarboxylation and transcarboxylation reactions. Here, we have used sodium dodecyl sulfate polyacrylamide gel electrophoresis and electroblotting followed by probing with avidin to identify biotin-containing polypeptides in Dictyostelium discoideum. Twenty biotinyl polypeptides were visualized, with a 23 kDa protein appearing transiently. Based upon the molecular mobility of the biotinyl polypeptides, D. discoideum may contain the biotin-dependent enzymes acetyl CoA carboxylase, proprionyl CoA carboxylase, pyruvate carboxylase, and 3-methylcrotonyl CoA carboxylase.
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PMID:Endogenous biotinylated proteins in Dictyostelium discoideum. 167 51

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

Biotin in high doses was given for 1-2 years to three diabetic patients suffering from severe diabetic peripheral neuropathy. Within 4-8 weeks there was a marked improvement in clinical and laboratory findings. It is suggested that in diabetes may exist a deficiency, inactivity or unavailability of Biotin, resulting in disordered activity of biotin-dependent enzyme, pyruvate carboxylase, leading to accumulation of pyruvate and/or depletion of aspartate, both of which play a significant role in nervous system metabolism. Based on our good results, regular biotin administration could be suggested for every diabetic patient for the prevention and management of peripheral neuropathy although extensive randomised clinical trials are required.
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PMID:Biotin for diabetic peripheral neuropathy. 208 65

Biotin deficiency can be induced readily in monogastric animals and is accompanied by characteristic abnormalities. These include dermal lesions involving hyper- and parakeratosis and, in fur-bearing animals, alopecia and achromatricia. Biochemical changes include depressions in the activities of biotin-dependent enzymes and the metabolic pathways in which they are involved. However, it has been shown in chickens that the relative changes in the activities of these enzymes and the resultant manifestations of the deficiency can be markedly influenced by the dietary content of other nutrients such as protein or fat. Biochemical criteria are required for the diagnosis of subclinical deficiency and these are best-established for poultry. Blood pyruvate carboxylase activity is a good criterion in young birds. Biotin-responsive disorders have been identified in several species. The etiology of fatty liver and kidney syndrome in chickens is now largely understood and is an interesting example of how a combination of nutritional and environmental factors can result in sudden death in, until then, apparently healthy animals.
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PMID:Assessment of biotin deficiency in animals. 286 81

Biotin-dependent carboxylases require covalently bound biotin for enzymatic activity. The biotin is attached through a lysine residue, which in a number of bacterial, avian, and mammalian carboxylases, is found within the conserved sequence Ala-Met-Lys-Met. We have determined the partial nucleotide sequence of cDNA clones for human propionyl-CoA carboxylase and pyruvate carboxylase. The predicted amino acid sequence of both these proteins contains the conserved tetrapeptide 35 residues from the carboxy terminus. In addition, both proteins contain the tripeptide, Pro-Met-Pro, 26 residues toward the amino terminus from the biotin attachment site. The overall amino acid homology through this region is 43%. Similar findings have been made for the biotin-containing polypeptides of transcarboxylase of Propionibacterium shermanii and acetyl-CoA carboxylase of Escherichia coli (W. L. Maloy, B. U. Bowien, G. K. Zwolinski, K. G. Kumar, and H. G. Wood (1979) J. Biol. Chem. 254, 11615-11622). The implications of this sequence conservation with regard to the function and evolution of biotin-dependent carboxylases is discussed. We propose that the 60 amino acids surrounding the biotin site are bounded by a proline "hinge" and the carboxy terminus has remained conserved as a result of constraints imposed by biotinylation of the enzyme.
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PMID:Sequence homology around the biotin-binding site of human propionyl-CoA carboxylase and pyruvate carboxylase. 355 48

Data from 116 females previously fed a corn-soybean basal diet with 0 or 220 micrograms supplemental biotin/kg during growth and development were used to study the influence of 0 (NB) or 440 (SB) micrograms of supplemental biotin/kg to corn-(C) or wheat-(W) based diets for gilts and sows housed in total confinement. Reproductive performance through four parities (total of 245 litters) and various sow and pig biochemical criteria were evaluated. Females fed W diets were older (P less than .07) at first estrus, farrowed litters that were lighter weight (P less than .01) at birth and that contained fewer (P less than .05) total and live pigs compared with females fed C diets. Biotin supplementation did not significantly influence (P greater than .10) farrowing and lactation performance; however, after the first parity, total and live pigs/litter at farrowing tended to be larger for SB females. Conception rate at first estrus postpartum was increased (P less than .07) by 9% and the average weaning to estrus interval was reduced (P less than .05) from 14.5 to 10.2 d with SB. Biotin supplementation increased (P less than .001) the biotin content of sow plasma, milk and liver, while sow liver pyruvate carboxylase activity was not altered (P greater than .10). Pigs farrowed by SB females had three- and fivefold higher (P less than .001) levels of plasma biotin at birth and 14 d of age, respectively; however, liver biotin levels at birth were not different (P greater than .10) for pigs from NB and SB females.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Supplemental biotin for swine. II. Influence of supplementation to corn- and wheat-based diets on reproductive performance and various biochemical criteria of sows during four parities. 397 36

Cell-free extracts of Bacillus licheniformis were found to contain pyruvate carboxylase which catalyzes the reaction between pyruvate and bicarbonate to yield oxalacetate in the presence of adenosine triphosphate (ATP), acetylcoenzyme A (CoA), and manganese. The plot between the reaction velocity of the carboxylation by the partially purified pyruvate carboxylase (25-fold) and the concentration of pyruvate, bicarbonate, manganese, and ATP did not indicate a pronounced deviation from the Michaelis-Menten hyperbola. The enzyme was inhibited by avidin and aspartate. Biotin partially protected the enzyme from avidin inhibition, whereas the amount of inhibition by aspartate was dependent on the concentration of acetyl-CoA present. The intracellular concentration of acetyl-CoA did not vary significantly enough to allow control of the enzyme by this method. Extracts of 4-hr postexponential-phase cells of B. licheniformis were also found to contain phosphoenolpyruvate carboxykinase, which appears to be under catabolite repression control. It is suggested that the endogenous induction of this enzyme is the determining factor allowing the shift to gluconeogenesis from glycolysis during sporulation of glucose-grown cells.
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PMID:Characterization and regulation of pyruvate carboxylase of Bacillus licheniformis. 505 52

Biotin containing carboxylases in cultured human skin fibroblasts were radioactively labeled by addition of [8,9-3H]biotin to biotin-depleted cell cultures. Three major bands were visualized by fluorography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the fibroblast proteins. These bands corresponded to pyruvate carboxylase (Mr = 125,000), the biotin-containing subunit of methyl crotonyl-CoA carboxylase (Mr = 75,000) and the biotin-containing subunit of propionyl-CoA carboxylase (Mr = 73,000) as judged by molecular weight markers, purified carboxylase protein standards, and interaction with monospecific antisera. Four out of 5 cell lines from patients with classical pyruvate carboxylase deficiency (less than 5% of normal activity) labeled with this technique displayed a normal band in the position of pyruvate carboxylase while one cell line showed complete absence of any labeled protein in this area. These results demonstrate heterogeneity in the etiology of pyruvate carboxylase deficiency.
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PMID:[3H]biotin-labeled proteins in cultured human skin fibroblasts from patients with pyruvate carboxylase deficiency. 640 85

Biotin-responsive multiple carboxylase deficiency can be categorized by clinical criteria into a neonatal-onset disorder and distinct syndrome of infantile onset. Pedigrees in each instance are consistent with autosomal recessive inheritance. For a neonatal-onset proband, the sensitivity to relative biotin deprivation and the rapid clinical response to biotin supplementation are reflected by in vitro studies. Specific activities of biotin-dependent pyruvate carboxylase, propionyl CoA carboxylase, and 1-methylcrotonyl CoA carboxylase are 0.8 to 16% of mean control values after growth of fibroblasts in intermediate and very low biotin concentrations. Following relative biotin depletion, pyruvate carboxylase activity returns to normal after only 14 hr of growth in biotin-supplemented medium. In contrast, carboxylase activities in fibroblasts of an infantile-onset proband remain normal at very low biotin concentrations, even when avidin is added to the growth medium. The clinical heterogeneity, taken together with the distinct responses of cultured skin fibroblasts to biotin deprivation in vitro, probably reflect fundamentally different etiologies for the two categories of biotin-responsive multiple carboxylase deficiency.
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PMID:Biochemical evidence for diverse etiologies in biotin-responsive multiple carboxylase deficiency. 680 81

Twenty-four pigs were weaned at four weeks of age and fed either spray dried egg albumen (DA) or autoclaved DA (ADA) as the only protein source were used to evaluate plasma and hepatic parameters as indicators of biotin status. Pigs were fed one of four semipurified diets during the 42-day study: DA basal, DA + 1.1 g sulfamethazine/day (DA + S), ADA basal or ADA + .5 mg biotin/day (ADA + H). Autoclaving DA at 121 degrees C for 30 minutes reduced both the biotin binding properties of the avidin fraction and the trypsin inhibitor activity of DA. Pigs fed ADA and ADA + H had greater (P less than .05) liver pyruvate carboxylase (EC 6.4.1.1) activity and DNA concentrations, lower (P less than .05) plasma urea nitrogen levels and greater and more efficient (P less than .05) weight gain than either DA or DA + S fed pigs. Biotin supplementation further enhanced (P less than .05) liver DNA concentration but had no effect on the liver levels of RNA or total protein. Plasma levels of glucose and free fatty acids or blood levels of lactate and pyruvate were not influenced by the addition of biotin to the ADA basal diet.
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PMID:The biotin status of weanling pigs fed semipurified diets as evaluated by plasma and hepatic parameters. 685 58


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