GO_REF:0000002

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Gss annotations including ATP binding; ligase activity.

"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."

GO_REF:0000024

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Gss annotations including ATP binding; glutathione binding; magnesium ion binding; protein homodimerization activity.

"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."

GO_REF:0000120

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Gss annotations including glutathione biosynthetic process; glutathione synthase activity.

"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."

GO_REF:0000121

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Gss annotations including ATP binding; glutathione binding; glutathione biosynthetic process; glutathione synthase activity; identical protein binding; magnesium ion binding; and other terms.

"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."

PMID:7862666

Amino acid sequence of rat kidney glutathione synthetase.

For Gss, this publication was assessed for annotations including glutathione synthase activity; identical protein binding.

"Glutathione (GSH) synthetase ... an enzyme present in almost all cells, catalyzes the ATP-dependent synthesis of GSH from gamma-L-glutamyl-L-cysteine and glycine."

PMID:10964706

Novel kinetics of mammalian glutathione synthetase: characterization of gamma-glutamyl substrate cooperative binding.

For Gss, this publication was assessed for annotations including ATP binding; glutathione binding; glutathione biosynthetic process; glutathione synthase activity; glycine binding; and other terms.

"Glutathione (GSH) synthetase ... catalyzes the final step in GSH biosynthesis."

PMID:16011481

Tumour necrosis factor alpha induces co-ordinated activation of rat GSH synthetic enzymes via nuclear factor kappaB and activator protein-1.

For Gss, this publication was assessed for annotations including response to tumor necrosis factor.

"TNFalpha induces the expression and recombinant promoter activities of GCLC, GCLM and GSS in H4IIE cells."

PMID:18653662

Coordinated changes in xenobiotic metabolizing enzyme gene expression in aging male rats.

For Gss, this publication was assessed for annotations including response to xenobiotic stimulus.

"Toluene exposure decreased the expression of glutathione synthetase, and dramatically increased the number of phase III genes being downregulated."

PMID:19212806

High fat feeding and dietary L-arginine supplementation differentially regulate gene expression in rat white adipose tissue.

For Gss, this publication was assessed for annotations including response to amino acid; response to nutrient levels.

"In contrast, Arg supplementation reduced mRNA levels for fatty acid binding protein 1, glycogenin, protein phosphates 1B, caspases 1 and 2, and hepatic lipase, but increased expression of PPARgamma, heme oxygenase 3, glutathione synthetase, insulin-like growth factor II, sphingosine-1-phosphate receptor, and stress-induced protein."

file:rat/Gss/Gss-deep-research-falcon.md

Falcon (Edison Scientific) deep research report: rat Gss (glutathione synthetase, P46413)

Gss is the second and final enzyme of de novo glutathione biosynthesis, catalyzing the ATP-dependent ligation of glycine to gamma-glutamylcysteine to form glutathione.

"**Glutathione synthetase (GSS; EC 6.3.2.3)** catalyzes the **ATP-dependent ligation of glycine** to **γ-glutamylcysteine (γ-GC)** to form **glutathione (GSH)** (chen2007relationshipofglutathione pages 16-20)."
Glutathione synthetase is the second (final) enzyme in the canonical two-step de novo biosynthesis of glutathione, a major low-molecular-weight cellular thiol antioxidant.

"**Glutathione synthetase (GSS; gene symbol Gss)** is the **second (final) enzyme** in the canonical two-step de novo biosynthesis of glutathione (GSH), a major low-molecular-weight cellular thiol antioxidant (chen2007relationshipofglutathione pages 16-20, tandon2024unravelingthemultifaceted pages 1-2)."
The core substrates are gamma-glutamylcysteine, glycine, and ATP; the product is glutathione, with strong substrate specificity for glycine ligation to gamma-glutamylcysteine.

"• Core substrates are γ-glutamylcysteine, glycine, and ATP. • Product is glutathione (GSH), the major low-molecular-weight cellular thiol antioxidant. • Literature supports strong substrate specificity for glycine ligation to γ-glutamylcysteine."
Glutathione biosynthesis occurs in the cytosol, with GSH subsequently distributed to organelles including mitochondria; rat Gss most directly acts in the cytosolic compartment.

"At the cell-biological level in animals, glutathione synthesis is generally described as occurring in the **cytosol**, with **GSH subsequently distributed to organelles**, including mitochondria (levonen2000glutathione pages 17-21, tandon2024unravelingthemultifaceted pages 1-2). This implies that rat Gss (P46413) most directly exerts its catalytic function in the **cytosolic compartment**, while influencing mitochondrial and other organelle redox capacity **indirectly via GSH availability** (tandon2024unravelingthemultifaceted pages 1-2)."
GSS catalyzes the non-rate-limiting second step after GCL; when GSS activity is inadequate, gamma-glutamylcysteine can be diverted to 5-oxoproline/pyroglutamate.

"A clinically important metabolic consequence of inadequate GSS activity is that **γ-glutamylcysteine may be diverted to oxoproline (5-oxoproline/pyroglutamate)**, contributing to **oxoproline accumulation and metabolic acidosis**, worsening glutathione deficiency (chen2007relationshipofglutathione pages 16-20)."