Selenoprotein P in Human Plasma as an Extracellular Phospholipid Hydroperoxide Glutathione Peroxidase

Abstract

Selenoprotein P is an extracellular protein containing presumably 10 selenocysteines that are encoded by the UGA stop codon in the open reading frame of the mRNA. The function of selenoprotein P is currently unknown, although several indirect lines of evidence suggest that selenoprotein P is a free radical scavenger. We first developed a conventional procedure to isolate selenoprotein P from human plasma. Next, we investigated the reactivities of selenoprotein P against various hydroperoxides in the presence of glutathione. Although selenoprotein P reduces neither hydrogen peroxide nor tertiary butyl hydroperoxide, it does reduce phospholipid hydroperoxide such as 1-palmitoyl-2-(13-hydroperoxy-cis-9,trans-11-octadecadienoyl)-3-phosphatidylcholine hydroperoxide. Kinetic analysis demonstrated a tert-uni ping-pong mechanism, similar to those described for classical glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase. Not only glutathione, but also dithiothreitol, mercaptoethanol, cysteine, and homocysteine, were effective as reducing substances, as in the case of phospholipid hydroperoxide glutathione peroxidase. These results show that selenoprotein P functions as a phospholipid hydroperoxide glutathione peroxidase in extracellular fluids.

Low selenium status is associated with the occurrence of the pregnancy disease preeclampsia in women from the United Kingdom

“…28 Selenoprotein P concentrations in plasma are known to be a useful marker of selenium status though neither circulating nor tissue concentrations of selenoprotein P have been measured in human pregnancy. In a UK study, selenoprotein P and plasma GPx together were found to account for up to 90% of total plasma selenium (cited in reference 26).…”

The yeast prion protein Ure2: Structure, function and folding

“…These enzyme families share the GSH binding thioredoxin domain, but are otherwise structurally and mechanistically dissimilar. In particular, GPxs contain a selenocysteine, which reacts covalently with GSH, generally via a ping-pong enzyme reaction mechanism [50]. In contrast, GSTs use a conserved tyrosine, serine or cysteine residue to interact with the thiol group of GSH, thus increasing the reactivity of GSH, typically via a sequential mechanism [51][52][53].…”

Lipid peroxidation and 4-hydroxy-2-nonenal formation by copper ion bound to amyloid-β peptide

“…Human Aβ and Aβ were purchased from Peptide Institute Inc. (Osaka, Japan); Aβ 1-28 , 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl) phosphatidylcholine (PLPC-OOH) was prepared from PLPC as described previously (18,32,33). Other chemicals were of the highest quality commercially available.…”