The quantitatively most important precursor of prostaglandins (PGs),
thromboxanes (TXs), prostacyclin (PGI2), and hydroxylated fatty
acids in the kindey is arachidonic acid (5,8,11,14 eicosatetraenoic acid).
Arachidonic acid is converted by the enzyme complex cyclooxygenase
into cyclized compounds (prostanoids), or by lipoxygenase and mixedfunction
oxidase into hydroxylated fatty acids with three or four double
bonds, including the leukotrienes (LTs) (Fig. 1). Other C20 fatty acids
can serve as precursors, such as 8,11,14 eicosatrienoic or 5,8,11,14,17
eicosapentaenoic acid. Eicosatrienoic acid is present in mammalian
tissues in much smaller quantities than arachidonic acid, and its metabolites
(PGEI, PGFI~, TXB1 ) are very much less abundant than the
arachidonic acid metabolites (Knapp et al. 1978). Although it was
recently shown that LTs can be formed from all-cis-5,8,11,14,17
eicosapentaenoic acid (Hammerstr6m 1980), this fatty acid is a poor
substrate for cyclooxygenase (and probably for lipoxygenase as well),
and, if converted to biologically active oxygenated metabolites the
amounts formed are exceedingly small (Sies et al. 1984; Fischer and
Weber 1984). Also, the renal C22 precursor fatty acid 7,10,13,16 docosatetraenoic
acid has been poorly studied but appears not to contribute
significantly to renal synthesis of oxygenated fatty acids (Tobias
et al. 1975). Thus, arachidonic acid remains the most abundant and
best-studied precursor and will alone be considered in this review.
It gives rise to the bisenoic prostanoids, i.e., prostanoids with two
double bonds, and to LTs (see Fig. I).