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Literature summary for 1.5.1.7 extracted from

  • Al-Saryi, N.; Al-Hejjaj, M.; Van Roermund, C.; Hulmes, G.; Ekal, L.; Payton, C.; Wanders, R.; Hettema, E.
    Two NAD-linked redox shuttles maintain the peroxisomal redox balance in Saccharomyces cerevisiae (2017), Sci. Rep., 7, 11868 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.5.1.7

Cloned(Commentary)

Cloned (Comment) Organism
gene LYS1, recombinant expression of GFP-tagged Lys1p in glucose-grown cells, it colocalizes with the peroxisomal marker HcRed-PTS1, recombinant expression of the enzyme in mdh3/gpd1DELTA cells and mislocation to the cytosol Saccharomyces cerevisiae

Protein Variants

Protein Variants Comment Organism
additional information generation of a mdh3/gpd1DELTA double mutant that accumulates saccharopine and displays lysine bradytrophy. Lysine biosynthesis is restored when saccharopine dehydrogenase is mislocalised to the cytosol in mdh3/gpd1DELTA cells. Recombinantly expressed GFP-tagged Lys1p colocalizes with the peroxisomal marker HcRed-PTS1 in glucose-grown cells. A disruption of the peroxisomal NAD+/NADH ratio as a consequence of a block in the redox shuttles leads to an increase in the Lys1p substrate/product ratio. The saccharopine/lysine ratio increases in mdh3/gpd1DELTA cells by more than 80fold. When Lys1p is mislocalised to the cytosol in mdh3/gpd1DELTA cells, the cytosolic pool of NAD+ supports Lys1p activity and lysine biosynthesis is restored. A decrease of saccharopine dehydrogenase activity (Lys1p-activity) causes lysine bradytrophy in mdh3/gpd1DELTA cells Saccharomyces cerevisiae

Localization

Localization Comment Organism GeneOntology No. Textmining
peroxisome peroxisomal matrix, the enzyme has a peroxisomal targeting signal type 1 (PTS1) Saccharomyces cerevisiae 5777
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Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O Saccharomyces cerevisiae
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 L-lysine + 2-oxoglutarate + NADH + H+
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 r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O Saccharomyces cerevisiae ATCC 204508
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 L-lysine + 2-oxoglutarate + NADH + H+
-
 r

Organism

Organism UniProt Comment Textmining
Saccharomyces cerevisiae P38998
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-
Saccharomyces cerevisiae ATCC 204508 P38998
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
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 Saccharomyces cerevisiae L-lysine + 2-oxoglutarate + NADH + H+
-
 r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
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 Saccharomyces cerevisiae ATCC 204508 L-lysine + 2-oxoglutarate + NADH + H+
-
 r

Synonyms

Synonyms Comment Organism
LYS1
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 Saccharomyces cerevisiae
Lys1p
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 Saccharomyces cerevisiae
NAD+-linked saccharopine dehydrogenase
-
 Saccharomyces cerevisiae

Cofactor

Cofactor Comment Organism Structure
NAD+
-
 Saccharomyces cerevisiae
NADH
-
 Saccharomyces cerevisiae

General Information

General Information Comment Organism
malfunction single mutants in MDH3 or GPD1 grow on lysine-deficient medium, but an mdh3/gpd1DELTA double mutant accumulates saccharopine and displays lysine bradytrophy. Lysine biosynthesis is restored when saccharopine dehydrogenase is mislocalised to the cytosol in mdh3/gpd1DELTA cells. A decrease of saccharopine dehydrogenase activity (Lys1p-activity) causes lysine bradytrophy in mdh3/gpd1DELTA cells Saccharomyces cerevisiae
metabolism in Saccharomyces cerevisiae, the ultimate step in lysine biosynthesis, the NAD+-dependent dehydrogenation of saccharopine to lysine, is a NAD+-dependent reaction performed inside peroxisomes. The availability of intraperoxisomal NAD+ required for saccharopine dehydrogenase activity can be sustained by both shuttles, the malate/oxaloacetate shuttle and a glycerol-3-phosphate dehydrogenase 1(Gpd1p)-dependent shuttle. The shuttles both are able to maintain the intraperoxisomal redox balance. The extent to which each of these shuttles contributes to the intraperoxisomal redox balance may depend on the growth medium. The presence of multiple peroxisomal redox shuttles allows eukaryotic cells to maintain the peroxisomal redox status under different metabolic conditions. During growth on glucose medium, saccharopine dehydrogenase (Lys1p) is the only lysine biosynthetic enzyme that is dependent on the availability of intraperoxisomal NAD+ Saccharomyces cerevisiae
physiological function saccharopine dehydrogenase, encoded by the LYS1 gene, requires NAD+ for the production of lysine. Intraperoxisomal NAD+ is required for saccharopine dehydrogenase activity Saccharomyces cerevisiae