High impact information on TDH2

• Mutants deleted for both GPD1 and GPD2 do not produce detectable glycerol, are highly osmosensitive and fail to grow under anoxic conditions [1].
• In addition, GPD2 is induced under aerobic conditions by the addition of bisulfite which causes NADH accumulation by inhibiting the final, reductive step in ethanol fermentation and this induction is reversed by addition of acetaldehyde [1].
• Our studies reveal that this process is tightly regulated, since, surprisingly, despite a high degree of sequence homology (98% similarity and 96% identity), the Tdh3 but not the Tdh2 isoenzyme was S-thiolated [2].
• 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].
• The growth inhibition of respiratory incompetent cox18Delta cells lacking GPD2 is reversed by the addition of acetoin, an alternative sink for NADH oxidation [4].

Biological context of TDH2

• Whereas in the TDH2 promoter permanganate reactivity was entirely abolished, the reactivity at the GAL1 and GAL10 promoter regions was only moderately affected [5].
• These data demonstrate that the presence of a functional TDH2 or TDH3 allele is required for cell growth [6].
• Using a 2D-gel system to study protein carbonylation, it is shown in this work that both Tdh2p and Tdh3p isozymes were oxidized during exposure to H(2)O(2) [7].
• TDH2 is linked to MET3 on chromosome X of Saccharomyces cerevisiae [8].
• In our clone, we found upstream of MET3, the nucleotide sequence of the TDH2 gene (Holland and Holland, J. Biol. Chem. 255, 2596-2605, 1980) [8].

Anatomical context of TDH2

• Western immunoblot analysis of cell wall extracts and cytosol showed that Tdh2 and Tdh3 polypeptides are present in the cell wall, as well as in the cytosol, of exponentially growing cells [9].

Associations of TDH2 with chemical compounds

• A strain of Saccharomyces cerevisiae lacking the GPD2 gene, encoding one of the glycerol-3-phosphate dehydrogenases, grows slowly under anaerobic conditions, due to reductive stress caused by the accumulation of cytoplasmic NADH [10].
• Mutant strains lacking only a functional TDH2 allele or a TDH3 allele grow at 50 and 75% of the rate observed for wild type cells, respectively, when glucose is used as carbon source [6].
• As a consequence, ethanol formation in the gpd2 delta mutant was elevated by 13% [11].

Other interactions of TDH2

• Further evidence that protein S-thiolation is tightly regulated in response to oxidative stress is provided by the finding that the Tdh3 GAPDH isoenzyme, and not the Tdh2 isoenzyme, is S-thiolated following exposure to H(2)O(2) in vivo, whereas both GAPDH isoenzymes are S-thiolated when H(2)O(2) is added to cell-free extracts [12].

Analytical, diagnostic and therapeutic context of TDH2

• The anaerobic performance of gpd1 delta and gpd2 delta mutants of Saccharomyces cerevisiae was characterized and compared to that of a wild-type strain under well-controlled conditions by using a high-performance bioreactor [11].

References