Literature summary for 1.4.1.4 extracted from

Mara, P.; Fragiadakis, G.S.; Gkountromichos, F.; Alexandraki, D.
The pleiotropic effects of the glutamate dehydrogenase (GDH) pathway in Saccharomyces cerevisiae (2018), Microb. Cell Fact., 17, 170 .

Search for more literature for 1.4.1.4

Protein Variants

Protein Variants	Comment	Organism
K110L	a naturally occurring mutation responsible for the inactivation of the catalytic site of Gdh1	Saccharomyces cerevisiae

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
L-glutamate + H2O + NADP+	Saccharomyces cerevisiae	-	2-oxoglutarate + NH3 + NADPH + H+	-	r
L-glutamate + H2O + NADP+	Saccharomyces cerevisiae ATCC 204508	-	2-oxoglutarate + NH3 + NADPH + H+	-	r

Organism

Organism	UniProt	Comment	Textmining
Saccharomyces cerevisiae	P07262	-	-
Saccharomyces cerevisiae	P39708	-	-
Saccharomyces cerevisiae ATCC 204508	P07262	-	-
Saccharomyces cerevisiae ATCC 204508	P39708	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
additional information	phase specific degradation of Gdh1p and its substitution by Gdh3p in the NADP-GDH activity pool seems to be favorable under glucose deprivation	Saccharomyces cerevisiae
ubiquitination	Gdh1p can be a potential target of ubiquitin attachment. Residue Lys426 in the C-terminal box is essential for the observed stationary-phase-specific degradation of Gdh1p	Saccharomyces cerevisiae

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
L-glutamate + H2O + NADP+	-	Saccharomyces cerevisiae	2-oxoglutarate + NH3 + NADPH + H+	-	r
L-glutamate + H2O + NADP+	-	Saccharomyces cerevisiae ATCC 204508	2-oxoglutarate + NH3 + NADPH + H+	-	r

Synonyms

Synonyms	Comment	Organism
GDH1	-	Saccharomyces cerevisiae
Gdh1p	-	Saccharomyces cerevisiae
GDH3	-	Saccharomyces cerevisiae
Gdh3p	-	Saccharomyces cerevisiae
glutamate dehydrogenase 1	-	Saccharomyces cerevisiae
glutamate dehydrogenase 3	-	Saccharomyces cerevisiae
NADP-dependent glutamate dehydrogenase 1	-	Saccharomyces cerevisiae
NADP-dependent glutamate dehydrogenase 2	-	Saccharomyces cerevisiae
NADP-GDH 1	-	Saccharomyces cerevisiae
NADP-GDH 2	-	Saccharomyces cerevisiae

Cofactor

Cofactor	Comment	Organism	Structure
NADP+	-	Saccharomyces cerevisiae
NADPH	-	Saccharomyces cerevisiae

Expression

Organism	Comment	Expression
Saccharomyces cerevisiae	the regulation of GDH1 under glucose conditions is performed by nitrogen catabolite repressor (NCR)-sensitive activators, Leu3p and activators exclusive for respiratory growth such as the HAP complex that coordinates nuclear and mitochondrial gene expression. Under ethanol conditions, GDH1 derepression is mediated by the Gcn4 and Hap4 transcriptional activators and is amplified by Gln3	up

General Information

General Information	Comment	Organism
malfunction	contradictory roles of GDH1 and GDH2 (EC 1.4.1.2) in cold-growth defects in yeast strains. Concurrent ectopic overexpression of GDH1 and GDH2 compensate the observed accumulation of ROS. Specifically, glutamate can prevent cold-induced ROS accumulation through the synthesis of glutathione that requires glutamate as a precursor molecule and serves in ROS removal. The role of Gdh1p in transcriptional silencing is crucial through the proteolysis of H3 histone in yeast (H3-clipping in the N-tail). GDH1 deletion leads to decreased binding of Sir2 protein on the telomeres, causing elevated transcript levels of genes affected by the loss of the SIR complex. Upon GDH1 deletion, the elevated levels of 2-oxoglutarate, and not those of NADH, result in the observed telomeric silencing defects. Upon GDH1 deletion, a highly derepressed expression of DAL5, a NCR-sensitive gene that requires both Gat1 and Gln3 for its expression, is observed. GDH1 deletion causes ammonium accumulation, but surprisingly does not affect the subcellular distribution and the concentrations of glutamine as well as glutamate	Saccharomyces cerevisiae
metabolism	in Saccharomyces cerevisiae glutamate can be synthesized from 2-oxoglutarate and ammonium through the action of NADP-dependent glutamate dehydrogenase isozymes Gdh1 and Gdh3. Gdh1 and Gdh3 are evolutionarily adapted isoforms and cover the anabolic role of the GDH-pathway, role and function of the GDH pathway in glutamate metabolism, overview. The pleiotropic effects of GDH pathway in yeast biology highlight the importance of glutamate homeostasis in vital cellular processes. Isozyme Gdh1 is the primary (hyperbolic) NADP-GDH enzyme and isozyme Gdh3 the cooperative NADP-GDH enzyme in the GDH pathway of Saccharomyces cerevisiae. The constant expression of GDH1 implies that its transcription proceeds normally during the different growth phases including the diauxic shift, when yeast cells reprogram their metabolism to enter the respiration phase. But during the post-diauxic shift, the Gdh1p/Gdh3p ratio decreases and most of the NADP-GDH activity is attributed to Gdh3p. The decrease of the NADP-GDH activity in ethanol growing cells was initially referred to be controlled through post-translational modifications that can modulate the proportion of Gdh1p versus Gdh3p monomers that constitute the NADP-GDH pool. Synthesis of glutamate occurs through the action of NADP-GDH (encoded by GDH1 and GDH3 genes). NAD-GDH activity (encoded by GDH2, EC 1.4.1.2) is responsible for glutamate degradation and release of ammonium and 2-oxoglutarate	Saccharomyces cerevisiae
physiological function	isozyme Gdh1 is the primary (hyperbolic) NADP-GDH enzyme and isozyme Gdh3 the cooperative NADP-GDH enzyme in the GDH pathway of Saccharomyces cerevisiae. The allosteric regulation of NADP-GDH activity is influenced by 2-oxoglutarate and NADP, and not by small molecules (e.g. GTP, AMP) or amino acids. Role of the GDH path in ROS-mediated apoptosis. GDH2 (EC 1.4.1.2) genetically interacts with GDH3 and controls stress-induced apoptosis. The transcription of GDH3 occurs extensively during the stationary phase. The activity of Gdh3p presents a 20 to 140fold increment when cells are grown under aerobic conditions. Under these conditions the majority of the total NADP-GDH activity is attributed to Gdh3p monomers that can contribute up to 70% to the pool, especially when cells enter or remain in aerobic metabolism for several days. Under acetate/raffinose conditions with ammonia as the only nitrogen source, yeast cells lacking GDH3 gene has a significant impairment in glutamate synthesis. The increase of the NADP-dependent GDH activity observed in gdh1DELTA mutants is presumably due to Gdh3p that seems to play a prominent role in glutamate metabolism under aerobic conditions. Glutamate synthesis under aerobic conditions is insufficient and requires additionally the activity of Gdh1p. The expression of both GDH3 and GDH1 is required to achieve wild-type growth in respiration. The transcriptional regulation of GDH3 is controlled by carbon sources and not by nitrogen catabolite repression as in the case of GDH1. The glucose-repressed expression of GDH3 is attributed to the condensed chromatin organization of its promoter	Saccharomyces cerevisiae
physiological function	isozyme Gdh1 is the primary (hyperbolic) NADP-GDH enzyme and isozyme Gdh3 the cooperative NADP-GDH enzyme in the GDH pathway of Saccharomyces cerevisiae. The allosteric regulation of NADP-GDH activity is influenced by 2-oxoglutarate and NADP, and not by small molecules (e.g. GTP, AMP) or amino acids. Role of the GDH path in ROS-mediated apoptosis. Role of GDH1 and GDH2 (EC 1.4.1.2) in glutamate synthesis and its possible implication to oxidation stress defense through the glutathione system. GDH1 regulates chromatin through its catalytic activity. The expression of both GDH3 and GDH1 is required to achieve wild-type growth in respiration. The transcriptional regulation of GDH3 is controlled by carbon sources and not by nitrogen catabolite repression as in the case of GDH1. The regulation of GDH1 under glucose conditions is performed by nitrogen catabolite repressor (NCR)-sensitive activators, Leu3p and activators exclusive for respiratory growth such as the HAP complex that coordinates nuclear and mitochondrial gene expression. Under ethanol conditions, GDH1 derepression is mediated by the Gcn4 and Hap4 transcriptional activators and is amplified by Gln3	Saccharomyces cerevisiae

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Release 2023.1 (January 2023)