PMID- 10362749
OWN - NLM
STAT- MEDLINE
DCOM- 19990722
LR  - 20181207
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 276
IP  - 6
DP  - 1999 Jun
TI  - Kinetic profile of the rat CYP4A isoforms: arachidonic acid metabolism and
      isoform-specific inhibitors.
PG  - R1691-700
LID - 10.1152/ajpregu.1999.276.6.R1691 [doi]
AB  - 20-Hydroxyeicosatetraenoic acid (HETE), the cytochrome P-450 (CYP) 4A
      omega-hydroxylation product of arachidonic acid, has potent biological effects on
      renal tubular and vascular functions and on the control of arterial pressure. We 
      have expressed high levels of the rat CYP4A1, -4A2, -4A3, and -4A8 cDNAs, using
      baculovirus and Sf 9 insect cells. Arachidonic acid omega- and
      omega-1-hydroxylations were catalyzed by three of the CYP4A isoforms; the highest
      catalytic efficiency of 947 nM-1. min-1 for CYP4A1 was followed by 72 and 22
      nM-1. min-1 for CYP4A2 and CYP4A3, respectively. CYP4A2 and CYP4A3 exhibited an
      additional arachidonate 11,12-epoxidation activity, whereas CYP4A1 operated
      solely as an omega-hydroxylase. CYP4A8 did not catalyze arachidonic or linoleic
      acid but did have a detectable lauric acid omega-hydroxylation activity. The
      inhibitory activity of various acetylenic and olefinic fatty acid analogs
      revealed differences and indicated isoform-specific inhibition. These studies
      suggest that CYP4A1, despite its low expression in extrahepatic tissues, may
      constitute the major source of 20-HETE synthesis. Moreover, the ability of CYP4A2
      and -4A3 to catalyze the formation of two opposing biologically active
      metabolites, 20-HETE and 11, 12-epoxyeicosatrienoic acid, may be of great
      significance to the regulation of vascular tone.
FAU - Nguyen, X
AU  - Nguyen X
AD  - Department of Pharmacology, New York Medical College, Valhalla, New York 10595,
      USA.
FAU - Wang, M H
AU  - Wang MH
FAU - Reddy, K M
AU  - Reddy KM
FAU - Falck, J R
AU  - Falck JR
FAU - Schwartzman, M L
AU  - Schwartzman ML
LA  - eng
GR  - DK-38226/DK/NIDDK NIH HHS/United States
GR  - HL-34300/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fatty Acids)
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (Protein Isoforms)
RN  - 0 (Recombinant Proteins)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 5DOQ38R4UW (11,12-epoxy-5,8,14-eicosatrienoic acid)
RN  - 79551-86-3 (20-hydroxy-5,8,11,14-eicosatetraenoic acid)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.14.15.3 (Cytochrome P-450 CYP4A)
RN  - FC398RK06S (8,11,14-Eicosatrienoic Acid)
SB  - IM
MH  - 8,11,14-Eicosatrienoic Acid/analogs & derivatives/metabolism
MH  - Animals
MH  - Arachidonic Acid/antagonists & inhibitors/*metabolism
MH  - Catalysis
MH  - Cell Line
MH  - Cytochrome P-450 CYP4A
MH  - Cytochrome P-450 Enzyme System/*metabolism/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Fatty Acids/metabolism
MH  - Female
MH  - Hydroxyeicosatetraenoic Acids/metabolism
MH  - Hydroxylation
MH  - Insecta
MH  - Kinetics
MH  - Male
MH  - Mixed Function Oxygenases/*metabolism/pharmacology
MH  - Oxidation-Reduction/drug effects
MH  - Protein Isoforms/antagonists & inhibitors/metabolism
MH  - Rats
MH  - Recombinant Proteins
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1152/ajpregu.1999.276.6.R1691 [doi]
PST - ppublish
SO  - Am J Physiol. 1999 Jun;276(6):R1691-700. doi: 10.1152/ajpregu.1999.276.6.R1691.