CATALYTIC PROPERTIES OF RABBIT KIDNEY FATTY-ACID OMEGA-HYDROXYLASE CYTOCHROME-P-450KA2 (CYP4A7)

We have examined in detail the substrate specificity of a rabbit kidne y fatty acid omega-hydroxylase, designated cytochrome P-450ka2 (CYP4A7 ). The hydroxylation products were identified as omega- and (omega - 1 )-hydroxy fatty acids mainly using gas chromatography-electron impact mass spectrometry. [1] Straight-chain saturated fatty acids ranging fr om 10 to 19 carbons were effectively hydroxylated at the omega- and (o mega - 1)-position. The ratios of omega- to (omega - 1)-hydroxylation activity decreased with increasing the carbon chain length of fatty ac ids. [2] Both isomyristate and anteisomyristate, and isopalmitate were hydroxylated several fold more rapidly than myristate and palmitate, respectively, with iso-branched chain fatty acids being hydroxylated a t the omega-position solely. [3] Both palmitoleate and palmitoelaidate , and both oleate and elaidate were hydroxylated much more rapidly tha n palmitate and stearate, respectively. [4] Linoleate, gamma-linolenat e, and arachidonate were also excellent substrates for this enzyme. [5 ] Prostaglandin (PG) A1 and PGA2 were efficiently hydroxylated at the omega-position solely, with PGE1 and PGE2 being much less active. [6] Arachidonic acid not only showed a K(m) value significantly lower than those for lauric acid, gamma-linolenic acid and PGA1, but also it is a potent competitor for lauric acid and PGA1, showing a very high affi nity for the enzyme. It is possible that arachidonic acid is the physi ological substrate for kidney P-450ka2.