Tissue-specific functions of individual glutathione peroxidases.
The family of glutathione peroxidases comprises four distinct mammalian selenoproteins. The classical enzyme (cGPx) is ubiquitously distributed. According to animal, cell culture and inverse genetic studies, its primary function is to counteract oxidative attack. It is dispensible in unstressed animals, and accordingly ranks low in the hierarchy of glutathione peroxidases. The gastrointestinal isoenzyme (GI-GPx) is most related to cGPx and is exclusively expressed in the gastrointestinal tract. It might provide a barrier against hydroperoxides derived from the diet or from metabolism of ingested xenobiotics. The extreme stability in selenium deficiency ranks this glutathione peroxidase highest in the hierarchy of selenoproteins and points to a more vital function than that of cGPx. Plasma GPx (pGPx) behaves similar to cGPx in selenium deficiency. It is directed to extracellular compartments and is expressed in various tissues in contact with body fluids, e.g., kidney, ciliary body, and maternal/fetal interfaces. It has to be rated as an efficient extracellular antioxidant device, though with low capacity because of the limited extracellular content of potential thiol substrates. Phospholipid hydroperoxide glutathione peroxidase (PHGPx), originally presumed to be a universal antioxidant enzyme protecting membrane lipids, appears to have adopted a variety of specific roles like silencing lipoxygenases and becoming an enzymatically inactive structural component of the mitochondrial capsule during sperm maturation. Thus, all individual isoenzymes are efficient peroxidases in principle, but beyond their mere antioxidant potential may exert cell- and tissue-specific roles in metabolic regulation, as is evident for PHGPx and may be expected for others.
Brigelius-Flohé
R
R
German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany. flohe@www.dife.de
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D002319:Cardiovascular System / Q000378:metabolism; D004064:Digestive System / Q000201:enzymology; D005979:Glutathione Peroxidase / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010545:Peroxides / Q000378:metabolism; D011506:Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051140:Selenoproteins; D015398:Signal Transduction; D013091:Spermatogenesis / Q000502:physiology; D014018:Tissue Distribution
D000975:Antioxidants; D010545:Peroxides; D011506:Proteins; D012333:RNA, Messenger; D051140:Selenoproteins; D005979:Glutathione Peroxidase