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)

Several mutants of Bacillus subtilis were isolated which sporulate continually during exponential growth in glucose medium. The spdA1 mutation, responsible for the continual sporulation of one of the mutants, mapped near thr. When an exponentially growing culture of a strain containing spdA1 was maintained at essentially constant turbidity, 5% of the viable cells contained heat-resistant spores. The continual sporulation depended on the stringent response since it was absent in spdA relA double mutants. Genetic and biochemical analysis indicated that the continual sporulation of spdA1 strains was associated with a lower specific activity of pyruvate carboxylase, which limited the rate of oxaloacetate synthesis from glucose via pyruvate and thereby the supply of compounds depending on the citrate cycle, especially aspartate. Therefore, the mild stringent response caused by the spdA1 mutation seems to result from a partial deficiency of aspartyl-tRNA which may exert its sporulation-initiating effect during a limited time interval in each growth cycle. A mutant blocked in fumarase activity (citG) behaved similarly. It grew only slowly in glucose medium because much of the limiting oxaloacetate was wasted for the excretion of fumarate. The mutant produced little aspartate and sporulated at a high frequency in glucose medium, even in the presence of glutamate; the sporulation was again prevented by aspartate or malate or by introduction of the relA marker into the strain.
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PMID:Properties of a Bacillus subtilis mutant able to sporulate continually during growth in synthetic medium. 640 59

The Saccharomyces cerevisiae gene BPL1 encodes the enzyme biotin:protein ligase (BPL), which is required for acetyl-CoA carboxylase (ACC) holoenzyme formation. Disruption of one of the two BPL1 alleles present in diploid cells results, upon sporulation, in a 2+:2(0) segregation of cell viability, with none of the two viable spores being BPL1 negative. In contrast to BPL1 deletants, BPL1 base-substitution mutants are potentially viable and may be isolated as long-chain-fatty-acid-requiring auxotrophs. In addition to ACC pyruvate carboxylase and an additional biotin-containing protein of unknown function fail to be biotinylated in BPL1-defective yeast mutants. In this study, one of these mutants, bpl1-C25/17, is shown to contain an amber stop codon at position 151 of the 689-amino-acid BPL sequence. In bpl1-C25/17 cells, de novo fatty acid synthesis is almost absent (< 2% of the wild type), while very-long-chain fatty acid (VLCFA) synthesis and, to some extent, medium-long-chain fatty acid elongation are still active. Hence, endogenous malonyl-CoA synthesis is reduced but not abolished by the translational stop mutation. A low rate of intact-BPL synthesis is accomplished in the mutant by occasional readthrough of the bpl1-C25/17 UAG nonsense triplet by normal yeast tRNA(Gln)(CAG). Correspondingly, ACC biotinylation is severely reduced though not completely absent in the two bpl1 mutants studied in this work. Residual BPL1 expression in bpl1-C25/17 cells is increased to a level allowing wild-type-like growth by transformation with high copy numbers of either the wild-type tRNA(Gln)(CAG) or the mutant bpl1-C25/17 genes. It is concluded that the lethality of BPL1 deletants is due to the lack of malonyl-CoA-dependent VLCFA synthesis and that the viability of distinct ACC-defective point mutants is due to their maintenance of a critical level of malonyl-CoA and, hence, VLCFA production. The residual capacity of malonyl-CoA synthesis, though, is inadequate to allow cytoplasmic bulk de novo fatty acid synthesis, nor does it support mutant growth on 13:0 as the only dietary fatty acid. ACC-defective mutants are respiratory deficient, which is attributed to the failure of mitochondrial fatty acid synthesis. Since lipoic acid levels of ACC1 and BPL1 mutants are essentially normal, an unknown product of mitochondrial fatty acid synthesis appears to be critically reduced in malonyl-CoA-deficient yeast cells.
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PMID:Pleiotropic phenotype of acetyl-CoA-carboxylase-defective yeast cells--viability of a BPL1-amber mutation depending on its readthrough by normal tRNA(Gln)(CAG). 968 62