Glutathione transferase, GST

The assessment of clearance is complicated by the numerous mechanisms by which compounds may be cleared from the body. These mechanisms include oxidative metabolism, most commonly by CYP enzymes, but also in some cases by other enzymes including but not limited to monoamine oxidases (MAO), flavin-containing monooxygenases (FMO), and aldehyde oxidase [45, 46], Non-oxidative metabolism such as conjugation or hydrolysis may be effected by enzymes such as glucuronyl transferases (UGT), glutathione transferases (GST), amidases, esterases, or ketone reductases, as well as other enzymes [47, 48], In addition to metabolic pathways, parent compound may be excreted directly via passive or active transport processes, most commonly into the urine or bile. 

OrganosuUur compounds have been shown to modulate the activity of glutathione -transferases (GST), a family of enzymes important in detoxification of carcinogens [24], and cytochromes P450 (CYP), a family of enzymes that activate many chemical carcinogens in experimental animals [25]. The effect of proteases inhibition is a new aspect of the biological activity of these plants and further research should be carried out to identify the specific compounds from Allium or Allium products that are responsible for this biochemical effect. 

It was recently discovered that 5. cerevisiae Ubrlp and Ufd4p, the E3 components of two distinct Ub-dependent proteolytic pathways, directly interact with specific proteins of the 26S proteasome (1). These results stemmed from the initial finding that overexpression of some subunits of the 19S particle inhibited ubiquitin-dependent degradation of engineered N-end rule substrates. To determine whether this effect could be caused by interaction of these subunits with a component(s) of the N-end rule pathway, glutathione transferase (GST)-pulldown assays with Ubrlp (also called... 

The glutathione transferases (GST), together with the tripeptide glutathione (GSH), conjugate the highly reactive and potentially... 

Affinity chromatography (AC) is a fractionation technique widely used in targeted proteomics or protein-protein interaction approaches. This method utilizes an interaction or affinity of a target protein to a substrate (or another protein) immobilized on a support matrix. Figure 17.4 demonstrates that AC can be incorporated into 3D proteomic approaches (Lee and Lee, 2004). Traditionally, AC has been used to purify, for example, carbohydratebinding proteins from Diplostomum pseudo-spathaceum (Mikes and Man, 2003) and the detoxification superfamily glutathione transferase (GST) from parasitic flatworms (Brophy and Barrett, 1990), specifically shown in... 

In light of the antioxidant, anti-inflammatory, and antiamyloid effects, curcumin has become a candidate compound for the prevention or treatment of AD [Calabrese et al., 2007]. Treatment of astrocytes with curcumin induced the cytoprotective proteins HO-1, NAD(P)H quinone oxidoreductase 1 (NQOl), and glutathione transferase (GST) and provided protection against... 

Fig. 6. (Opposite page) A high-throughput production method for screening proteins from cDNA libraries. Authentic (A) and glutathione -transferase (GST)-fused (G) proteins in the reaction mixtures after a semi-automated polymerase chain reaction/ transcription and translation from 54 different cDNAs separated by sodium dodecyl sul-fide-polyaciylamide gel electrophoresis and stained with Coomassie Brilliant Blue. T and S, respectively, mark total translation product and the supernatant fraction after centrifugation at 30,000g for 15 min.

Grisham et al. 1990 Baker and Baker 1992). Induction and expression of UDP-glucuronosyltransferase (UGT1A1) and glutathion-transferase GST Al were studied in CACO-2 cells (Svchlikova et al. 2004). 

Figure 13.6. Glutathione -transferases (GST), chromosomal location, and their substrates. GSTa, GST(x, GSTco, and GST0 classes have multiple genes. GST proteins within the same class have approximately 50% identical amino acid sequences.

Glutathione transferases (GST) are enzymes involved in detoxification processes. They catalyze the conjugation between toxic compounds and glutathione (GSH, 3 in Fig. 5.3A) as a preliminary step to biological elimination. Several classes of... 

The glutathione transferase (GST) comprises multifunctional proteins coded by a multigene family. These enzymes are both cytosolic and microsomal and function as homodimers and heterodimers. They exist as four classes in mammals. The human enzymes comprise the following dimers Al-1, Al-2, A2-2, A3-3 (alpha class), Mla-la, Mla-lb, Mlb-lb, Mla-2, M2-2, M3-3 (mu class), Pl-1 (pi class), Tl-1 (theta class), and three microsomal enzymes (MIC). The GST Al-1 and Al-2 are also known as ligandin when they act as binding or carrier proteins, a property also displayed by Mla-la, Mlb-lb and also by GSH (pi class). 

DATS which are potent inhibitors of BP-induced fore-stomach cancer in mice, resulted in a significant increase, as compared with control, in bodi hepatic (3.0-, 3.2-and 4.4-fold, respectively) and fore-stomach (1.5-, 2.7-and 2.7-fold, respectively) glutathione transferase (GST) activity toward anti-7P,8a-dihy oxy-9a, 1 Oa-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (anti-BPDE), which is the ultimate carcinogen of BP [102, 107]. On the contrary, this activity was not increased in either organ by dipropyl sulfide (DPS), which is ineffective against BP-induced fore-stomach cancer. The pulmonary GST activity was not increased by any of the tested OSCs. Even though epoxide hydrolase (EH) activity was differentially altered by these OSCs, a correlation between chemopreventive efficacy of OSCs and their effects on EH activity was not apparent [102]. The chemopreventive efficacy of these OSCs correlated with their ability to increase the expression of GST n. For example, DAS treatment resulted in approximate increases of 1.7- and 2.2-fold in hepatic and fore-stomach GST n expression, respectively, over the control. Treatment of mice with DATS, which is a relatively more potent inhibitor of BP-induced fore-stomach cancer than DAS, resulted in about 3.8- and 3,2-fold increases, respectively, in hepatic and fore-stomach GST n expression over the control. On the contrary, the expression of hepatic and fore-stomach GST n was increased only marginally (10-20%) upon DPS administration [107],... 

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