Disease relevance of PDC1

• In this recombinant, the coding region of pyruvate decarboxylase 1 (PDC1) was completely deleted, and two copies of the D-lactate dehydrogenase (D-LDH) gene from Leuconostoc mesenteroides subsp. mesenteroides strain NBRC3426 were introduced into the genome [1].
• The yeast PDC1 gene was expressed in Escherichia coli, leading to an active PDC [2].

High impact information on PDC1

• Using potassium permanganate, which preferentially modifies single-stranded DNA, we show that a temperature-sensitive rad25(ts) mutant severely reduces the normally extensive promoter melting observed in vivo on the highly expressed genes TDH2 and PDC1 and on the induced heat shock gene HSP82 [3].
• This decarboxylation can be effected by any of Pdc1p, Pdc5p, Pdc6p, or Ydr380wp; Ydl080cp has no role in the catabolism of either amino acid [4].
• Mutant studies showed that one of the decarboxylases encoded by PDC1, PDC5, PDC6, YDL080c, or YDR380w must be present to allow yeast to utilize alpha-keto-beta-methylvalerate [5].
• For this purpose we studied the function of different promoter fragments of PDC1, encoding the major pyruvate decarboxylase enzyme in wild-type cells, in the basal CYC1 promoter context [6].
• ERA, a novel cis-acting element required for autoregulation and ethanol repression of PDC1 transcription in Saccharomyces cerevisiae [6].

Chemical compound and disease context of PDC1

• The upstream region of the Saccharomyces cerevisiae pyruvate decarboxylase structural gene, PDC1, has been isolated and fused to the indicator gene Escherichia coli lacZ [7].

Biological context of PDC1

• Recently we deleted the pyruvate decarboxylase structural gene PDC1 from the genome of the yeast Saccharomyces cerevisiae [8].
• Autoregulation may control the expression of yeast pyruvate decarboxylase structural genes PDC1 and PDC5 [8].
• The predicted amino acid sequences of PDC1 and PDC5 are 88% identical [8].
• From the DNA sequence of the intragenic region TRX1 is 500 bp downstream of PDC1 [9].
• These results indicate that pyruvate decarboxylase encoded by the PDC1 gene contributes, at least partially, to the decarboxylation of alpha-KIC for isoamyl alcohol formation [10].

Anatomical context of PDC1

• According to sequence analysis, ADH1 and PDC1 are most likely cytoplasmatic proteins, while ADH2 is most probably localized in the mitochondria [11].

Associations of PDC1 with chemical compounds

• Deletion of either of these genes has little or no effect on the specific pyruvate decarboxylase activity, but enzyme activity is undetectable in mutants lacking both PDC1 and PDC5 (S. Hohmann and H. Cederberg, Eur. J. Biochem. 188:615-621, 1990) [12].
• Spontaneous mutants, derived from such a pdc1 pdc5 strain, were isolated which could again ferment glucose [13].
• Hence, under thiamine limitation both PDC1 and PDC5 are expressed [14].
• Experiments with cell extracts from S. cerevisiae mutants expressing a single PDC gene demonstrated that both PDC1- and PDC5-encoded isoenzymes can decarboxylate branched-chain 2-oxo acids [15].
• Fructose also induced PDC1 transcription, indicating that intracellular sugars could act as trigger for PDC1 induction or, alternatively, that two inductors are present [16].

Physical interactions of PDC1

• Gel retardation and oligonucleotide competition experiments suggest that the DNA binding factor TUF interacts with the RPG box in the upstream region of PDC1 [17].

Regulatory relationships of PDC1

• The second copy of PDC6 was expressed under the control of the PDC1 promoter, which was still present in the pdc1 strain [13].
• Deletion of the more strongly expressed PDC1 gene stimulates the promoter activity of both PDC1 and PDC5, a phenomenon called Pdc autoregulation [18].

Other interactions of PDC1

• Two structural genes, PDC1 and PDC5 have been characterized [12].
• PDC6, a weakly expressed pyruvate decarboxylase gene from yeast, is activated when fused spontaneously under the control of the PDC1 promoter [13].
• The DNA binding protein Pdc2 was initially identified as a regulator of the genes PDC1 and PDC5, which encode isoforms of the glycolytic enzyme pyruvate decarboxylase (Pdc) [19].
• (i) The glucose-inducible fermentation genes PDC1 and ADH1 share the sequence ATACCTTCSTT [20].
• Transcriptional induction of the PDC1 gene (encoding pyruvate decarboxylase) was observed after glucose or galactose pulses were applied to the pgi1 strain, demonstrating that metabolism of these sugars beyond glucose 6-phosphate is dispensable for PDC1 induction [16].

Analytical, diagnostic and therapeutic context of PDC1

• Northern blot analysis revealed that a sequence in the yeast genome homologous to PDC1 and formerly designated as a possible pseudogene is expressed and may code for a different but closely related pyruvate decarboxylase [21].

References