Glutathione compartmentation

Smith CV, Jones DP, Guenther TM, et al. Compartmentation of glutathione implications for the study of toxicity and disease. Toxicol AppI Pharmacol 1996 140 1-12. 

Compartmentation of glutathione has been demonstrated in that a separate pool of glutathione exist in the cytoplasm from that in the mitochondria (Figure 18.6). The cytosolic pool of glutathione has been characterized in terms of cellular protection (Table 18.1). 

Catalase Catalase reacts very rapidly with hydrogen peroxide, converting it to water. It is located in the cytoplasm of erythrocytes but compartmentalized in the peroxisomes of most other cells. Catalase is especially concentrated in liver and erythrocytes, but is low in brain, heart and skeletal muscle. The normal low concentrations of hydrogen peroxide production are efficiently reduced in cells by glutathione peroxidase. However, if the concentration of hydrogen peroxide is raised, catalase becomes important. 

Plate 3 Compartmentation of biosynthesis and sequestration. Abbreviations SM, secondary metabolites GS-SM, conjugate of SM with glutathione NPAAs, non-protein amino acids ATP, adenosine triphosphate ADP, adenosine diphosphate mt, mitochondrium cp, chloroplast nc, nucleus 1, passive transport 2, free diffusion 3, H+/SM antiporter 4, ABC transporter for SM conjugated with glutathione 5, ABC transporter for free SM 6, H+-ATPase. (Fig. 1.4, p. 9)... 

Studies aiming to solve the importance of the cellular compartmentation of glutathione are a very interesting field of research, as pointed out by Sies [6]. 

Bellomo G,VairettiM, Stivala L,Mirabelli F, Richelmi P,Orrenius S (1992) Demonstration of nuclear compartmentalization of glutathione in hepatocytes. Proc Natl Acad Sci USA 89 4412-4416... 

Gopalakrishna R, Chen Z-H, Gundimeda U. 1997a. Selenocompounds induce a redox modulation of protein kinase C in the cell, compartmentally independent from cytosolic glutathione Its role in inhibition of tumor promotion. Arch Biochem Biophys 348(l) 37-48. 

SLATER, T.F. (editor) (1978) Biochemical Mechanisms of Liver Injury (London Academic Press). SMITH, C.V., JONES, D.P., GUENTHER, T.M., LASH, L.H. and LAUTERBURG, B.H. (1996) Compartmentation of glutathione implications for the study of toxicity and disease. Tox. Appl. Pharmacol, 140 1. 

Plant biotransformation parallels liver biotransformation and is conceptually divided into three phases. Phase I typically consist of oxidative transformations in which polar functional groups such as OH, NH2, or SH are introduced. However, reductive reactions have been observed for certain nitroaromatic compounds. Phase II involves conjugation reactions that result in the formation of water soluble compounds such as glucosides, glutathiones, amino acids, and malonyl conjugates or water-insoluble compounds that are later incorporated or bound into cell wall biopolymers. In animals, these water-soluble Phase H metabolites would typically be excreted. In Phase III, these substances are compartmentalized in the plant vacuoles or cell walls. For additional details, the reader is referred to reviews on the subject by Komossa and Sandermann (1995), Pflugmacher and Sandermann (1998), and Burken (2003). Enzymatic conversion rates typically follow Michaelis-Menten kinetics and are temperature-dependent (Larsen et al., 2005 Yu et al., 2004,2005, 2007). 

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