Tags

Type your tag names separated by a space and hit enter

Activation of carbonyl reductase from pig lung by fatty acids.
Arch Biochem Biophys. 1992 Feb 01; 292(2):548-54.AB

Abstract

The NADPH-linked reductase activity of pig lung carbonyl reductase was activated two- to fivefold by fatty acids with a carbon chain length greater than nine at pH 7.0. cis-Unsaturated fatty acids of C:18 and C:20 were potent activators, showing Ka values of 2-14 microM which were lower than the values of 21-125 microM for saturated fatty acids (C:9 to C:16). Of the fatty acids arachidonic acid (C20:4) gave the highest activation. No significant stimulatory effect was observed with acyl CoAs, fatty alcohols, phospholipids, and nonionic detergents. Anionic detergents (sodium dodecyl sulfate and sarkosyl) stimulated the enzyme activity more than ninefold, but the Ka values for them were much higher than those for the cis-unsaturated fatty acids. Although no change in molecular weight or in subunit composition was observed in the enzyme activated by C20:4, the activation led to a decrease in thermal stability of the enzyme. The binding of C20:4 to the enzyme was instantaneous and reversible, shifted the pH optimum of the activity from 5.8 to 6.5, and changed the inhibitor sensitivity. In addition, C20:4 acted as an allosteric effector abolishing the negative interaction of the enzyme with carbonyl substrates which was seen without the fatty acid, but the activation increased both Vmax and [S]0.5 values for the substrates. Kinetic analysis with respect to NADPH concentration, in which no cooperativity was detected with or without C20:4, indicated that C20:4 was a nonessential activator of mixed type showing a binding constant of 10 microM. These results suggest that cis-unsaturated fatty acids may be potential modulators of pulmonary carbonyl reductase.

Authors+Show Affiliations

Department of Biochemistry, Gifu Pharmaceutical University, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1731617

Citation

Hara, A, et al. "Activation of Carbonyl Reductase From Pig Lung By Fatty Acids." Archives of Biochemistry and Biophysics, vol. 292, no. 2, 1992, pp. 548-54.
Hara A, Oritani H, Deyashiki Y, et al. Activation of carbonyl reductase from pig lung by fatty acids. Arch Biochem Biophys. 1992;292(2):548-54.
Hara, A., Oritani, H., Deyashiki, Y., Nakayama, T., & Sawada, H. (1992). Activation of carbonyl reductase from pig lung by fatty acids. Archives of Biochemistry and Biophysics, 292(2), 548-54.
Hara A, et al. Activation of Carbonyl Reductase From Pig Lung By Fatty Acids. Arch Biochem Biophys. 1992 Feb 1;292(2):548-54. PubMed PMID: 1731617.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of carbonyl reductase from pig lung by fatty acids. AU - Hara,A, AU - Oritani,H, AU - Deyashiki,Y, AU - Nakayama,T, AU - Sawada,H, PY - 1992/2/1/pubmed PY - 1992/2/1/medline PY - 1992/2/1/entrez SP - 548 EP - 54 JF - Archives of biochemistry and biophysics JO - Arch. Biochem. Biophys. VL - 292 IS - 2 N2 - The NADPH-linked reductase activity of pig lung carbonyl reductase was activated two- to fivefold by fatty acids with a carbon chain length greater than nine at pH 7.0. cis-Unsaturated fatty acids of C:18 and C:20 were potent activators, showing Ka values of 2-14 microM which were lower than the values of 21-125 microM for saturated fatty acids (C:9 to C:16). Of the fatty acids arachidonic acid (C20:4) gave the highest activation. No significant stimulatory effect was observed with acyl CoAs, fatty alcohols, phospholipids, and nonionic detergents. Anionic detergents (sodium dodecyl sulfate and sarkosyl) stimulated the enzyme activity more than ninefold, but the Ka values for them were much higher than those for the cis-unsaturated fatty acids. Although no change in molecular weight or in subunit composition was observed in the enzyme activated by C20:4, the activation led to a decrease in thermal stability of the enzyme. The binding of C20:4 to the enzyme was instantaneous and reversible, shifted the pH optimum of the activity from 5.8 to 6.5, and changed the inhibitor sensitivity. In addition, C20:4 acted as an allosteric effector abolishing the negative interaction of the enzyme with carbonyl substrates which was seen without the fatty acid, but the activation increased both Vmax and [S]0.5 values for the substrates. Kinetic analysis with respect to NADPH concentration, in which no cooperativity was detected with or without C20:4, indicated that C20:4 was a nonessential activator of mixed type showing a binding constant of 10 microM. These results suggest that cis-unsaturated fatty acids may be potential modulators of pulmonary carbonyl reductase. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/1731617/Activation_of_carbonyl_reductase_from_pig_lung_by_fatty_acids_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0003-9861(92)90029-V DB - PRIME DP - Unbound Medicine ER -