Department of Biotechnology & Microbiology, Kannur University, Thalassery Campus, Palayad, India.
Chem Biol Drug Des. 2012 Sep;80(3):434-9. doi: 10.1111/j.1747-0285.2012.01418.x. Epub 2012 Jun 27.
Ester bond hydrolysis of membrane phospholipids by Phospholipase A(2) and consequent release of fatty acids are the initiating steps of inflammation. It is proposed in this study that the inhibition of phospholipase A(2) is one of the ways to control inflammation. Investigations are carried out to identify the mode of inhibition of phospholipase A(2) by the n-hexadecanoic acid. It may help in designing of specific inhibitors of phospholipase A(2) as anti-inflammatory agents. The enzyme kinetics study proved that n-hexadecanoic acid inhibits phospholipase A(2) in a competitive manner. It was identified from the crystal structure at 2.5 Å resolution that the position of n-hexadecanoic acid is in the active site of the phospholipase A(2). The binding constant and binding energy have also been calculated using Isothermal Titration Calorimetry. Also, the binding energy of n-hexadecanoic acid to phospholipase A(2) was calculated by in silico method and compared with known inhibitors. It may be concluded from the structural and kinetics studies that the fatty acid, n-hexadecanoic acid, is an inhibitor of phospholipase A(2), hence, an anti-inflammatory compound. The inferences from the present study validate the rigorous use of medicated oils rich in n-hexadecanoic acid for the treatment of rheumatic symptoms in the traditional medical system of India, Ayurveda.
通过磷脂酶 A(2)水解膜磷脂中的酯键，并随后释放脂肪酸，是炎症的起始步骤。本研究提出抑制磷脂酶 A(2)是控制炎症的途径之一。研究旨在确定十六烷酸抑制磷脂酶 A(2)的模式。这可能有助于设计特定的磷脂酶 A(2)抑制剂作为抗炎剂。酶动力学研究证明，十六烷酸以竞争性方式抑制磷脂酶 A(2)。通过 2.5Å 分辨率的晶体结构鉴定，十六烷酸位于磷脂酶 A(2)的活性部位。还使用等温滴定量热法计算了结合常数和结合能。此外，通过计算化学方法计算了十六烷酸与磷脂酶 A(2)的结合能，并与已知抑制剂进行了比较。通过结构和动力学研究可以得出结论，脂肪酸十六烷酸是磷脂酶 A(2)的抑制剂，因此也是一种抗炎化合物。本研究的推论证实了在印度传统医学体系阿育吠陀中，使用富含十六烷酸的药用油治疗风湿症状的严格应用。
