GPX4

The phospholipid hydroperoxide glutathione peroxidase ( PHGPx ) ( Gen: GPX4 ) is one of four previously known glutathione peroxidases, which degrades those complex hydroperoxides as part of the antioxidant defense system, which can result from the effects of free radicals. PHGPx is produced in all chordates and occurs in humans in several tissue types are present, but especially in the testicles. Three isoforms, which are localized in the cytosol, in the mitochondria, and the nucleus are known. Embryos without PHGPx die and mutations in GPX4 can cause infertility in men.

In mice, the tissue types of the highest expression of PHGPx in turn testis, heart, brain, small intestine, stomach, liver, duodenum, epididymis. In humans, this is not yet known exactly.

Function

PHGPx catalyses the oxidation of glutathione by lipid hydroperoxides. This reaction step makes the reactive (and therefore dangerous ) peroxide harmless, but decreases the reductive pool, which must be replenished by glutathione reductase again. PHGPx is indispensable for the development of neurons in the embryo, but also after craniocerebral trauma. Mice that produce only half PHGPx ( heterozygous knockout ), were more sensitive to oxidative stress, but lived longer.

PHGPx has in addition to its enzymatic function tasks as structural protein in sperm.

The expression of PHGPx is upregulated by C / EBPε induced by TNF. PHGPx is self-locking on NF-KB activation, and at several points of the prostaglandin synthesis.

History

The enzyme was discovered in 1982 by Fulvio Ursini and Mathilde Maiorino of the University of Padua. Genetic studies by Regina Brigelius - Flohé in Potsdam ( DIfE) delivered in 1993 to prove that it is a separate enzyme.

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