<p>Human Secretary Phospholipase A2 Mutations and Their Clinical Implications</p>

Abstract

Phospholipases A2 (PLA 2 s) belong to a superfamily of enzymes responsible for hydrolysis of the sn-2 fatty acids of membrane phospholipids to release arachidonic acid. PLA 2 s are the rate limiting enzyme for the downstream synthesis of prostaglandins and leukotrienes that are the main mediators of inflammation. The extracellular forms of this enzyme are also called the secretary phospholipase A2 (sPLA 2) and are distributed extensively in most of the tissues in the human body. Their integral role in inflammatory pathways has been the primary reason for the extensive research on this molecule. The catalytic mechanism of sPLA 2 is initiated by a histidine/aspartic acid/calcium complex within the active site. Though they are known to have certain housekeeping functions, certain mutations of sPLA 2 are known to be implicated in causation of certain pathologies leading to diseases such as atherosclerosis, cardiovascular diseases, benign fleck retina, neurodegeneration, and asthma. We present an overview of human sPLA 2 and a comprehensive compilation of the mutations that result in various disease phenotypes. The study not only helps to have a holistic understanding of human sPLA 2 mutations and their clinical implications, but is also a useful platform to initiate research pertaining to structure-function relationship of the mutations to develop effective therapies for management of these diseases.

Secretory Phospholipase A2 Enzymes in Acute Lung Injury

“…New studies are needed to identify potential interacting or binding molecules for these enzymes and characterize the resultant downstream signaling. (3) Understanding the mechanisms underlying sPLA 2 expression, secretion, and clearance under normal and pathological conditions would contribute to the development of new strategies to target the sPLA 2 s. (4) Several mutations in sPLA 2 enzymes have been associated with diseases such as atherosclerosis, cardiovascular disease, and asthma [ 65 ]. Recently a rare mutation (R123H) was also identified in sPLA 2 -IIA in two infants with ARDS [ 66 ].…”

Dynamic Role of Phospholipases A2 in Health and Diseases in the Central Nervous System

“…Under these conditions, sPLA2 are often induced together with the C-reactive protein and serve as markers of inflammation [ 76 ]. Studies have identified more than 10 isoforms of sPLA2 e.g., IB, IIA, IIC, IID, IIE, IIF, III, V, X and XIIA, which are distributed among different cell types and body organs [ 77 ]. The ribbon model of human group III sPLA2 showed three helices, one calcium binding loop, five disulfide bonds and His34 and Asp63 in the active site [ 77 ].…”

“…Studies have identified more than 10 isoforms of sPLA2 e.g., IB, IIA, IIC, IID, IIE, IIF, III, V, X and XIIA, which are distributed among different cell types and body organs [ 77 ]. The ribbon model of human group III sPLA2 showed three helices, one calcium binding loop, five disulfide bonds and His34 and Asp63 in the active site [ 77 ]. In the extracellular milieu, sPLA2s require high levels of calcium for activation [ 78 ].…”

2,6‐Pyridinedicarboxylic Acid (PDCA) Catalyzed Improved Synthetic Approach for 1‐Amidoalkyl Naphthols, Dihydropyrimidin‐2(1H)‐ones and Bis‐indoles

“…Indole based molecules have been considered in medicinal chemistry. Among those, bis-indole moieties commonly present in numerous drugs with biological actions such as antimicrobial, [55] antifungal, [55] human cancer cell lines, [56] phospholipase A2, [57] anti-inflammatory, [55] coronavirus A-59, [58] a calcineurin inhibitor, [56] anti-serotonin activity, [56] antiviral, [59] antiproliferative, [60] HIV [61] and anti-adipogenic [62] activities. Bisindole methane moieties also present in numerous alkaloids such as Hama Canthin, [63] Dragmacidin, [64] Rhopaladin, [58] Nortopsentin E, [65] Deoxytopsentin, [66] Gelliusines, [67] Dendridine, [68] Caulersin, [69] Caulerpin, [70] Chondriamides [71] and Gelliusin [72] and they are representing numerous biological actions.…”