5 p-CHOLESTANE · 3 a , 27-DIOL : NAD + OXIDOREDUCTASE AND 3 a-HYDROXY-5 p-CHOLESTAN-27-AL : NAD + OXIDOREDUCT ASE IN RAT LIVER EXTRACT * )
Using rat liver alcohol:NAD+ oxidoreductase and aldehyde:NAD+ oxidoreductase, the following facts were found: 1) 3a-hydroxy-5~-cholestan-27-al was reduced to 5fi -cholestane-3a, 27-diol by liver alcohol: NAD+ oxidoreductase. 2) The optimum pH was pH 7. 0 with potassium phosphate buffer and pH 8. 5 with Tris buffer. 3) The Km value of the substrate to the enzyme was 14. 3 μM. 4) 3a-Hydroxy5fi-cholestan-27al was oxidized to 3a-hydroxy5fi-cholestan27-oic acid by liver aldehyde: NAD+ oxidoreductase. 5) The optimum pH was pH 8. 5 with Tris buffer. 6) The Km value of the substrate to the enzyme was 26. 3 μM.
The formation of lithocholic acid, chenodeoxycholic acid and other bile acids from 3 beta-hydroxychol-5-enoic acid in vitro and in vivo.
Abstract Previous work has shown that 3β-hydroxycholenoic acid and several naturally occurring C 24 bile acids are formed from cholesterol incubated with rat-liver mitochondria. It is now shown that [ 3 H]3β-hydroxycholenoic acid is converted into lithocholic, chenodeoxycholic, 3α,6β-dihydroxycholanoic and β-muricholic acids in vitro . This suggests that 3β-hydroxycholenoic acid is an intermediate in the formation of C 24 bile acids from cholesterol in vitro . When [ 3 H]3β-hydroxycholenoic acid is injected intravenously into rats, 80% of the radioactivity is recovered in the bile within 2 h, mainly as lithocholic, chenodeoxycholic, 3α,6β-dihydroxycholanoic and β-muricholic acids. This raises the possibility that 3β-hydroxycholenoic acid lies on one of the pathways by which chenodeoxycholic acid is formed in vivo .
Stereoselective disposition of ibuprofen enantiomers in infants.
The pharmacokinetics of the enantiomers of ibuprofen were investigated after oral administration of a single 7.6 +/- 0.3 mg kg-1 dose of the racemate in 11 infants. Mean (+/- s.d.) half-lives were 1.6 +/- 0.5 h for S(+) and 1.5 +/- 0.5 h for R(-) and mean (+/- s.d.) AUC values were 31.5 +/- 14.3 mg l-1 h for S(+) and 36.6 +/- 13.8 mg l-1 h for R(-). Since plasma concentrations of the active S(+)-isomer were lower than those reported in adults, a higher dosage might be required in infants.