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Literature summary for 3.5.99.6 extracted from

  • Oikari, S.; Makkonen, K.; Deen, A.J.; Tyni, I.; Kaernae, R.; Tammi, R.H.; Tammi, M.I.
    Hexosamine biosynthesis in keratinocytes roles of GFAT and GNPDA enzymes in the maintenance of UDP-GlcNAc content and hyaluronan synthesis (2016), Glycobiology, 26, 710-722 .
    View publication on PubMed
Search for more literature for 3.5.99.6

Protein Variants

Protein Variants Comment Organism
additional information siRNA silencing of isozymes GNPDA1 and GDPDA2 with or withour simultanious silencing of glucosamine-6-phosphate (GlcN6P): glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) isozymes, phenotypes, overview. Analysis of influences of the siRNAs against genes regulating hexosamine biosynthesis on mRNA levels of GFAT1, GNPDA1, and GNPDA2 by quantitative RT-PCR expression analysis. Cell proliferation and migration following GFAT and GNPDA depletion Homo sapiens
additional information siRNA silencing of isozymes GNPDA1 and GDPDA2 with or without simultanious silencing of glucosamine-6-phosphate (GlcN6P):glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) isozymes, phenotypes, overview. Analysis of influences of the siRNAs against genes regulating hexosamine biosynthesis on mRNA levels of GFAT1, GNPDA1, and GNPDA2 by quantitative RT-PCR expression analysis. Cell proliferation and migration following GFAT and GNPDA depletion. GNPDA1 siRNA, while ineffective by itself, can largely prevent the influence of mannose on UDP-GlcNAc and hyaluronan synthesis, thus raising GNPDA1 as a specific candidate for the target of mannose. The finding that GNPDA1 siRNA does not counteract the mannose-induced depletion of cell surface hyaluronan suggests that in addition to GNPDA1 mannose may target cell surface receptor activity Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
alpha-D-glucosamine 6-phosphate + H2O Homo sapiens
-
 D-fructose 6-phosphate + NH3
-
 r
alpha-D-glucosamine 6-phosphate + H2O Homo sapiens in standard culture conditions keratinocyte GNPDAs mainly catalyze the reaction from GlcN6P back to Fru6P D-fructose 6-phosphate + NH3
-
 r

Organism

Organism UniProt Comment Textmining
Homo sapiens P46926
-
-
Homo sapiens Q8TDQ7
-
-

Source Tissue

Source Tissue Comment Organism Textmining
keratinocyte
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
alpha-D-glucosamine 6-phosphate + H2O
-
 Homo sapiens D-fructose 6-phosphate + NH3
-
 r
alpha-D-glucosamine 6-phosphate + H2O in standard culture conditions keratinocyte GNPDAs mainly catalyze the reaction from GlcN6P back to Fru6P Homo sapiens D-fructose 6-phosphate + NH3
-
 r

Synonyms

Synonyms Comment Organism
GNPDA1
-
 Homo sapiens
GNPDA2
-
 Homo sapiens

General Information

General Information Comment Organism
malfunction depletion of GFAT1 reduces the cellular pool of UDP-GlcNAc and hyaluronan synthesis, while simultaneous blocking of both isozymes GNPDA1 and GDPDA2 exerts opposite effects, indicating that in standard culture conditions keratinocyte GNPDAs mainly catalyze the reaction from GlcN6P back to Fru6P. When hexosamine biosynthesis is blocked by GFAT1 siRNA, the effect by GNPDAs is reversed, now catalyzing Fru6P towards GlcN6P, likely in an attempt to maintain UDPGlcNAc content. Silencing of these enzymes also changes the gene expression of related enzymes: GNPDA1 siRNA induces GFAT2 which is hardly measurable in these cells under standard culture conditions, GNPDA2 siRNA increases GFAT1, and GFAT1 siRNA increases the expression of hyaluronan synthase 2 (HAS2). Silencing of GFAT1 stimulates GNPDA1 and GDPDA2, and inhibites cell migration. The multiple delicate adjustments of these reactions demonstrate the importance of hexosamine biosynthesis in cellular homeostasis, known to be deranged in diseases like diabetes and cancer. GNPDA1 siRNA, while ineffective by itself, could largely prevent the influence of mannose on UDP-GlcNAc and hyaluronan synthesis, thus raising GNPDA1 as a specific candidate for the target of mannose. The finding that GNPDA1 siRNA does not counteract the mannose-induced depletion of cell surface hyaluronan suggests that in addition to GNPDA1 mannose may target cell surface receptor activity Homo sapiens
malfunction depletion of GFAT1 reduces the cellular pool of UDP-GlcNAc and hyaluronan synthesis, while simultaneous blocking of both isozymes GNPDA1 and GDPDA2 exerts opposite effects, indicating that in standard culture conditions keratinocyte GNPDAs mainly catalyze the reaction from GlcN6P back to Fru6P. When hexosamine biosynthesis is blocked by GFAT1 siRNA, the effect by GNPDAs is reversed, now catalyzing Fru6P towards GlcN6P, likely in an attempt to maintain UDPGlcNAc content. Silencing of these enzymes also changes the gene expression of related enzymes:GNPDA1 siRNA induces GFAT2 which is hardly measurable in these cells under standard culture conditions, GNPDA2 siRNA increases GFAT1, and GFAT1 siRNA increases the expression of hyaluronan synthase 2 (HAS2). Silencing of GFAT1 stimulates GNPDA1 and GDPDA2, and inhibites cell migration. The multiple delicate adjustments of these reactions demonstrate the importance of hexosamine biosynthesis in cellular homeostasis, known to be deranged in diseases like diabetes and cancer Homo sapiens
metabolism distinct contributions of glucosamine-6-phosphate (GlcN6P):glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) and glucosamine-6-phosphate deaminases (GNPDA1 and 2) isozymes to the UDP-GlcNAc pool of cultured keratinocytes, and their consequences to the hyaluronan synthesis, one of the cellular processes most dependent on cytosolic UDP-GlcNAc supply, and to cell proliferation and migration, overview Homo sapiens
metabolism distinct contributions of glucosamine-6-phosphate (GlcN6P):glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) and glucosamine-6-phosphate deaminases (GNPDA1 and 2)isozymes to the UDP-GlcNAc pool of cultured keratinocytes, and their consequences to the hyaluronan synthesis, one of the cellular processes most dependent on cytosolic UDP-GlcNAc supply, and to cell proliferation and migration, overview Homo sapiens