PLA1

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Introduction

Phospholipase forms a variety of enzymes, which are very different in structure and function, and can hydrolyze phospholipid (PL) substrates at specific ester bonds. There are two general sets of phospholipases, namely acyl hydrolases and phosphodiesterases; the enzymes in each set are then classified according to their specific cleavage of the ester bond. Acyl hydrolase is composed of phospholipase A1 (PLA1), phospholipase A2 (PLA2), phospholipase B (PLB) and lysophospholipase A1/2 (LysoPLA1/2), whereas the phosphodiesterases are represented by phospholipase C (PLC) and phospholipase D (PLD). Phospholipase is present in almost all cells, and many kinds of phospholipase are present in most cells. A given PL ester bond can be catalyzed by a variety of specific phospholipase subtypes, and they can exist in a secreted, membrane associated or cytoplasmic form. The physiological relevance of phospholipases can be attributed to three general functions: (1) they can act as digestive enzymes; (2) they can play an important role in the maintenance and remodeling of membranes; (3) they can regulate important cells mechanism. Among these phospholipases, PLA 2, PLC and PLD are the most studied, and they all play an important role in the production of biologically active lipid molecules.

Figure 1. Ester Bond Specificity of the Phospholipases. PLA1, PLA2, and PLC catalyze the hydrolysis of the ester bond emanating from the sn-1(1), sn-2 (2), and sn-3 (3) carbon, respectively (Richmond, G.S.; Smith, T.K. 2011)

Phospholipase A1

PLA 1 (EC 3.1.1.32) catalyzes the hydrolysis of FAs at the sn-1 position of PLs to generate a free fatty acid (FFA) and a lysophospholipid (lysoPL). PLA 1 has not yet obtained any crystal structure, so a lot of relevant information is still unknown. The synthesis and regulation mechanism of lysoPLs is not yet fully understood, which has become the reason why PLA 1 has been widely studied as it may be involved in their formation. The FA product from a PLA 1 reaction has the potential for biological activity, which has been confirmed in plants, that is, PLA 1 regulates the biosynthesis of jasmonic acid. In addition, it has been hypothesized for decades that the cleavage of sn-2 arachidonic acid (AA) from PLs may sometimes be mediated by the concerted sequential PLA 1 /LysoPLA 2 activities. No cloned PLA 1 is related to this alternative route, so it is circumstantial with regards to the in vitro studies, which provides the most indirect evidence.

More than a hundred years ago, people observed the accumulation of FFA when incubating pancreatic juice with phosphatidylcholine (PC), so the existence of enzymes responsible for the release of these acids was proposed. Early research on PLA mainly focused on PLA 2. However, type A phospholipase is linked to those enzymes that cleave FA from PL, and the names A 1 and A 2 are used to signify acyl hydrolysis from either the sn-1 or sn-2 position of the glycerol moiety, respectively. Subsequently, PLA activity was found in many organisms and tissues, opening the way for the possibility that these enzymes are not merely digestive catalysts.

Figure 2. Regulatory Processes Linked to PL Metabolism (Richmond, G.S.; Smith, T.K. 2011)

Classification of Phospholipase A1

PLA 1 specifically hydrolyzessn-1 acyl esters of PLs to produce FFAs and lysoPLs. However, many PLA 1 enzymes exhibit some, usually much lower, LysoPLA activity and neutral lipase activity, but thesn-1 cleavage site is still preferred. Therefore, enzymes with high PLA 1 relative to LysoPLA and neutral lipase activity are considered to be true PLA 1 enzymes. Since it is impossible to precisely determine which enzyme activities are present and how to distinguish particular enzyme activities, early studies involving the detection of PLA activity from crude tissue or subcellular fractions are flawed. PLA 1 is not officially classified like other major phospholipases. The main obstacle encountered was the lack of available sequences, as only a relatively small proportion of the PLA 1 enzyme has been cloned so far. The invariable feature of PLA 1 seems to be the lipase shared motif in the peptide sequence. The common GXSXG motif contains the catalytic serine at the active site, which functions as part of the catalytic triad.