Hydroxy/hydroperoxyeicosatetraenoic acids (FA0306)
From LipidomicsWiki
Arachidonic acid is also a precursor for hydroxyeicosatatraenoic acids (HETEs) and 9- and 20-hydroxyeicosatetraenoic acids are formed by cytochrome P450 enzymes in brain, lung, kidney and peripheral blood vessels and are known to play a role regulation in vascular tone in renal, cerebral and coronary circulation.
20-Hydroxyeicosatetraenoic acid (HETE) is a potent vasoconstrictor in vascular smooth muscle cells that is formed in reaction by ω-hydroxylation of arachidonic acid by enzymes of the CYP4A and CYP4F families and CYP4A11, CYP4F2 and CYP4F3B are considered to be major 20-HETE synthesis enzymes (Miyata et al 2005). 20-HETE is a vasoconstrictor that causes blockade of Ca2+-activated K+-channels, plays a role as a vascular oxygen sensor, in the thick ascending loop of Henle (TAHL), where it inhibits sodium transport via the sodium-potassium-two chloride co-transporter and Na+/H+ exchanger (Sacerdoti et al., 2003; Escalante et al. 1991; Good et al. 1999). 20-HETE also inhibits sodium reabsorption in kidney proximal tubules by reducing Na+/K+ ATPase activity (Quigley et al. 2000). It has been documented that in experimental rat models of hypertension the expression of enzymes of the CYP4A family and subsequently the generation of 20-HETE was elevated (Sacerdoti et al. 1989; Alonso-Garcia et al. 2002). Additionally, 20-HETE acts as a second messenger for parathyroid hormone, dopamine and angiotensin II, and also for serotonin and phenylephrine and in TAHL serves as a second messenger controlling potassium recycling and sodium uptake from the filtrate (Satarug et al. 2006, Sarkis et al. 2004). Besides 20-HETE other types can also synthesized through cytochrome P450 dependent pathway (see figure 21.)
