Disease relevance of PYC1

• In addition, we investigated the effects of the two changes in the Pyc2 biotin domain (K1155R substitution and Q1178P/five-amino-acid extension) on the extent of biotinylation in vivo by Escherichia coli biotin ligase, and compared the biotinylation of peptides containing these changes with that of two different-length Pyc1 biotin-domain peptides [1].
• Quaternary structure of pyruvate carboxylase from Pseudomonas citronellolis [2].
• We have employed phage display coupled with a genetic selection to identify determinants of the biotin domain (yPC-104) of yeast pyruvate carboxylase 1 (residues 1075-1178) required for interaction with BPL [3].

High impact information on PYC1

• These data suggest that in methylotrophic yeast pyruvate carboxylase plays a dual role in that, besides its well-characterized metabolic function as anapleurotic enzyme, the protein fulfils a specific role in the AO sorting and assembly process, possibly by mediating FAD-binding to AO monomers [4].
• We created a recombinant form of CIN8 that fused the biotin carrying polypeptide from yeast pyruvate carboxylase to the carboxyl terminus of Cin8p [5].
• The main physiological role of OAC appears to be to use the proton-motive force to take up into mitochondria oxaloacetate produced from pyruvate by cytoplasmic pyruvate carboxylase [6].
• The nucleotide sequence of the yeast pyruvate carboxylase gene has been determined from a cloned fragment of yeast genomic DNA [7].
• Double labeling studies with 3H- and 14C-labeled leucine confirm that pyruvate carboxylase is synthesized in the presence of lactate but not in the presence of aspartate [8].

Biological context of PYC1

• Concurrent expression from constitutive promoters of genes ICL1 and MLS1 (encoding malate synthase) also suppressed the growth phenotype of pyc1 pyc2 mutants [9].
• These enzymatic changes were independent of the nature of the carbon source and closely correlated to the changes in beta-galactosidase from PYC1-lacZ gene fusion and in PYC1 transcripts [10].
• Nevertheless, at the lowest ethanol fraction that supported growth of the Pyc- mutant, activities of the glyoxylate cycle enzymes in cell extracts were still sufficient to meet the requirement for C4-compounds in biomass synthesis [11].
• Regulation of pyruvate carboxylase isozyme (PYC1, PYC2) gene expression in Saccharomyces cerevisiae during fermentative and nonfermentative growth [12].
• We localized the previously isolated gene, which we designate PYC1, to chromosome VII [13].

Anatomical context of PYC1

• The subcellular location of hexose diphosphatase, phosphoenolpyruvate carboxykinase and pyruvate carboxylase in baker's yeast (Saccharomyces cerevisiae) was investigated by density gradient centrifugation of spheroplast lysates obtained by osmotic shock treatment of spheroplasts and centrifugation for 10000 g x min [14].
• Impact of temperature reduction and expression of yeast pyruvate carboxylase on hGM-CSF-producing CHO cells [15].
• Co-production with H. polymorpha pyruvate carboxylase (HpPyc1p) resulted in AO activation, but did not improve import into peroxisomes [16].
• In contrast, in S. cerevisiae, pyruvate carboxylase was found exclusively in the cytosol [17].
• It will be shown that introducing a pyruvate carboxylase gene expressed in the cytoplasma into a continuous BHK-21 cell line, and thus reconstituting the missing link between glycolysis and TCA, can reduce this problem [18].

Associations of PYC1 with chemical compounds

• DV6.2 (PYC1, pyc2 delta) showed a 3.2-fold higher level of activity on ethanol minimal medium when compared to growth on glucose minimal medium, and supported growth in the absence of L-aspartate [12].
• On ethanol minimal medium, the growth-related pattern of PYC1 and PYC2 expression was similar as shown by a 3.6-fold decline from early to mid log phase [12].
• Moreover, the pyc1 null showed a strong requirement for L-aspartate for efficient growth, indicating the importance of PYC1 expression for the synthesis of C4 intermediates [12].
• Transfer of exponentially growing cells of the pyc2 mutant from an aspartate or a glutamate medium to an ammonium medium caused a fivefold increase in PYC1 mRNA in less than 30 min, whereas in the inverse experiment, PYC1 transcripts returned within 30 min to the low levels found in aspartate/glutamate medium [10].
• In Pyc- as well as in wild-type cultures, levels of isocitrate lyase, malate synthase and phospho-enol-pyruvate carboxykinase in cell extracts decreased with a decreasing ethanol content in the feed [11].

Other interactions of PYC1

• The isolation was done starting with a triple mutant pyc1 pyc2 mth1 unable to grow in glucose-ammonium medium and selecting for mutants able to grow in the non-permissive medium [19].
• By the use of these mutants, evidence was obtained that in vivo the biotinylation of both acetyl-CoA carboxylase and pyruvate carboxylase is catalyzed by the same ligase [20].

Analytical, diagnostic and therapeutic context of PYC1

• On the basis of genetic crosses and complementation tests, we have attributed the defect to mutations in the PYC gene encoding pyruvate carboxylase [21].
• Improvement of the primary metabolism of cell cultures by introducing a new cytoplasmic pyruvate carboxylase reaction [18].

References