Imamura Y, Migita T, Anraku M, Otagiri M
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Biol Pharm Bull. 1999 Jul;22(7):731-3. doi: 10.1248/bpb.22.731.
The inhibition of rabbit heart carbonyl reductase (RHCR) by fatty acids was examined using 4-benzoylpyridine (4BP) as a substrate. The inhibitory potency of saturated fatty acids increased with elongation in the carbon chain from caprylic acid to myristic acid, but decreased with further elongation. Myristic acid with 14 carbon atoms most strongly inhibited RHCR. All of the unsaturated fatty acids tested strongly inhibited RHCR; the cis-isomers were more potent inhibitors than the corresponding trans-isomers. The methyl esters and alcohols, which lack a carboxyl group, derived from fatty acids did not exert a significant inhibitory effect on RHCR. These results indicate that the existence of a proper length of carbon chain, double bond(s), and a carboxyl group in a fatty acid molecule is important for RHCR inhibition. We also propose the possibility that myristic acid at low concentrations inhibits the reduction of 4BP by interacting with a binding site other than the coenzyme- and substrate-binding sites of RHCR.
以4-苯甲酰吡啶（4BP）作为底物，研究了脂肪酸对兔心脏羰基还原酶（RHCR）的抑制作用。饱和脂肪酸的抑制效力随着碳链从辛酸延伸至肉豆蔻酸而增强，但进一步延长则降低。含14个碳原子的肉豆蔻酸对RHCR的抑制作用最强。所有测试的不饱和脂肪酸均强烈抑制RHCR；顺式异构体比相应的反式异构体是更强效的抑制剂。源自脂肪酸的缺乏羧基的甲酯和醇对RHCR没有显著抑制作用。这些结果表明，脂肪酸分子中适当长度的碳链、双键和羧基的存在对于抑制RHCR很重要。我们还提出了一种可能性，即低浓度的肉豆蔻酸通过与RHCR辅酶和底物结合位点以外的结合位点相互作用来抑制4BP的还原。
