Pathway maps

Glutathione metabolism
Glutathione metabolism

Object List (links open in MetaCore):, GPX4 (PHGPx),,, L-Cysteinyl-glycine,, GSTT1 Homodimer, GSTM1 Homodimer, RX,,, (, GPX6, GSTK1 Homodimer, (L)-Cysteine,, Glutathione, MGST2 Homotrimer, GSTM2 Homodimer,, GSTA1 Homodimer or heterodimer of GSTA1 and GSTA2, MGST Homotrimer, OPLA Homodimer, GSTA4 Homodimer, GPX2 Homotetramer, Glycine, Gamma-(L)-glutamyl-(L)-cysteine, GSTT2 Homodimer, GPX5, GSHB, GSTM4 Homodimer, GSTO1 Homodimer, (L)-Glutamic acid, GSTM5 Homodimer, Glutathione disulfide, L-Amino acid, R-S-Glutathione,, GGT1, GSTA5 Homodimer, CD13, GGTL3, GSTA2 Homodimer or heterodimer of GSTA1 and GSTA2, R-S-Alanine, GSTO2, GPX3 Homotetramer,, GSTP1 Homodimer, GCL reg, GCL cat, GCTG, GPX7, Gamma-(L)- glutamyl-aminoacid, MGST3, GPX1 Homotetramer, GSHR,,, R-S-Alanylglycine,, 5-Oxo-(L)-proline, GSTM3 Homodimer, GSTA3 Homodimer, MAAI Homodimer


Glutathione metabolism

Glutathione can be found in the cell in oxidized ( Glutathione disulfide ) and reduced ( Glutathione ) form. Reduced glutathione can be either directly formed from Glutathione disulfide as the result of activity of Glutathione reductase ( GSHR ) [1], [2], or from conjugation of L-Cysteinyl-glycine with (L)-Glutamic acid catalyzed by Gamma-glutamyltranspeptidase 1 precursor ( GGT1 ) or by Gamma-glutamyltransferase light chain 2 ( GGTL3 ) [3].

L-Cysteinyl-glycine is formed as a result of glutathione conjugation to the L-Amino acid moiety catalyzed by GGT1 and GGTL3 [3]. This reaction results in formation of Gamma-(L)-glutamyl-aminoacid which is converted by Gamma-glutamylcyclotransferase ( GCTG ) [4], [5], [6] to the 5-Oxo-(L)-proline and L-Amino acid. 5-Oxo-(L)-proline is then reduced to (L)-Glutamic acid by 5-Oxoprolinase ( OPLA ) [7], [8], [9], (L)-Glutamic acid also produced in the Glutathione degradation during the R-S-Alanylglycine formation step.

5-Oxo-(L)-proline and (L)-Cysteine are produced as the result of Gamma-(L)-glutamyl-(L)-cysteine cleavage catalyzed by GCTG [6]. Gamma-(L)-glutamyl-(L)-cysteine itself is synthesized by Glutamate-cysteine ligase catalytic subunit ( GCL cat ) from (L)-Glutamic acid and from (L)-Cysteine [10], [11]. Glutathione synthetase ( GSHB ) catalyzes subsequent conjugation of Gamma-(L)-glutamyl-(L)-cysteine and Glycine to form Glutathione [12], [13]. Glycine is supplied from L-Cysteinyl-glycine degradation to Glycine and to (L)-Cysteine, as well as from the R-S-Alanylglycine degradation step.

Glutathione (reduced) reacts with various substrates ( RX ). Those reactions are carried out by a set of enzymes: Glutathione S-transferase A1 ( GSTA1 ), Glutathione S-transferase A2 ( GSTA2 ), Glutathione S-transferase A3 ( GSTA3 ), Glutathione S-transferase A4 ( GSTA4 ), Glutathione S-transferase A5 ( GSTA5 ) [14], [15], [16], [17], [18], [19], Glutathione S-transferase M1 ( GSTM1 ), Glutathione S-transferase M2 ( GSTM2 ) [20], [21], Glutathione S-transferase M3 ( GSTM3 ), Glutathione S-transferase M4 ( GSTM4 ), glutathione S-transferase M5 ( GSTM5 ) [22], [23], [24], [25], [26], [27], Glutathione transferase zeta 1 (maleylacetoacetate isomerase) ( MAAI ) [28], [29], Glutathione transferase omega-1 ( GSTO1 ), Glutathione transferase omega-2 ( GSTO2 ) [30], [31], Glutathione S-transferase theta-1 ( GSTT1 ), Glutathione S-transferase theta-2 ( GSTT2 ) [32], [33], Glutathione S-transferase kappa 1 ( GSTK1 ) [34], [35], Glutathione S-transferase pi 1 ( GSTP1 ) [36], [37], Microsomal glutathione S-transferase 1 ( MGST ), Microsomal glutathione S-transferase 2 ( MGST2 ), and Microsomal glutathione S-transferase 3 ( MGST3 ) [38], [27]. These reactions produce R-S-Glutathione (glutathione conjugated to a moiety) products. Subsequently R-S-Glutathione lose their (L)-Glutamic acid moieties in reactions catalyzed by GGT1 and GGTL3 [3] to produce R-S-Alanylglycine that is further degraded to R-S-Alanine by Aminopeptidase N ( CD13 ).

Glutathione disulfide can be formed directly from Glutathione in the reaction catalyzed by Glutathione peroxidase 4 ( GPX4 (PHGPx) ) [39], Glutathione peroxidase 1 ( GPX1 ) [40], [41], Glutathione peroxidase 2 ( GPX2 ) [42], [43], Glutathione peroxidase 3 (plasma) ( GPX3 ) [44], [45], Glutathione peroxidase 6 ( GPX6 ) [46], [47], Glutathione peroxidase 7 ( GPX7 ), Glutathione peroxidase 5 ( GPX5 ) [48] and GSHR.

Glutathione disulfide can also be formed through ascorbate metabolism.


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