Catalytic properties of rabbit kidney fatty acid omega-hydroxylase cytochrome P-450ka2 (CYP4A7).
We have examined in detail the substrate specificity of a rabbit kidney 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 from 10 to 19 carbons were effectively hydroxylated at the omega- and (omega - 1)-position. The ratios of omega- to (omega - 1)-hydroxylation activity decreased with increasing the carbon chain length of fatty acids. [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 at the omega-position solely. [3] Both palmitoleate and palmitoelaidate, and both oleate and elaidate were hydroxylated much more rapidly than palmitate and stearate, respectively. [4] Linoleate, gamma-linolenate, 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 Km 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 affinity for the enzyme. It is possible that arachidonic acid is the physiological substrate for kidney P-450ka2.
Toneyama Research Institute, Osaka City University Medical School and Toneyama Hospital, Japan.
A
A
Sawamura
E
E
Kusunose
K
K
Satouchi
M
M
Kusunose
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002384:Catalysis; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015786:Cytochromes b5 / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006900:Hydroxylation; D007672:Kidney Cortex / Q000201:enzymology*; D007700:Kinetics; D007850:Lauric Acids / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D011454:Prostaglandins A / Q000378:metabolism; D011817:Rabbits; D013379:Substrate Specificity
D005227:Fatty Acids; D007850:Lauric Acids; D010713:Phosphatidylcholines; D011454:Prostaglandins A; C030358:lauric acid; D016718:Arachidonic Acid; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; C100008:prostaglandin A2; C100573:prostaglandin A1