Metabolism of arachidonic acid by adult and fetal human liver microsomes and recombinant human CYP to epoxides/diols, 20-HETE, 19-HETE and other HETEs
Liver microsomes | Rate | Percent of total metabolites | ||||
---|---|---|---|---|---|---|
∑Epoxides/diols | ∑HETEs | ω2 | ω1 | ∑bis-HETEs and other HETEs2-a | ||
nmol/min/mg | % | |||||
HL37 | 0.35 | 37 | 41 | 8 | 14 | 19 |
HL42 | 0.31 | 31 | 32 | 3 | 13 | 16 |
HL46 | 0.36 | 28 | 27 | 4 | 8 | 15 |
FL1 | N.D. | 30 | 52 | 2 | 18 | 32 |
FL2 | 0.23 | 27 | 41 | 2 | 10 | 29 |
CYP | Rate | |||||
pmol/min/pmol | ||||||
CYP1A2 | 0.1 | 50 | 48 | 12 | 2 | 34 |
CYP3A4 | 0.2 | 41 | 51 | <2 | <1 | 49 |
CYP2C8 | 0.1 | 60 | 30 | <1 | <1 | 30 |
CYP2C19 | 1.5 | 38 | 31 | 19 | <1 | 11 |
CYP | Rate | Percent of total metabolites | ||||
∑Epoxides/diols | ∑HETEs | 13-HETE | 12-HETE | |||
pmol/min/pmol | % | |||||
CYP2C9 | 0.4 | 64 | 20 | 6 | 5 |
↵2-a bis-HETEs designates 13-HETE, 10-HETE, and 7-HETE. The 13-HETE peak on SP-HPLC could be contaminated with 18-HETE, 17-HETE and 16-HETE on its back shoulder (Brash et al., 1995), and other HETEs could also be formed in addition to the bis-HETEs.
N.D., not determined.
∑ designates sum of metabolites; HL, adult human liver; FL, fetal human liver. The recombinant enzymes and microsomes were incubated for 30 min except for CYP1A2 (120 min).