Phospholipase A<sub>1</sub> (EC 3.1.1.32; systematic name: phosphatidylcholine 1-acylhydrolase) encoded by the PLA<sub>1</sub>A gene is a phospholipase enzyme which removes the 1-acyl group:
It is an enzyme that resides in a class of enzymes called phospholipase that hydrolyze phospholipids into fatty acids. There are four classes, separated according to the type of reaction they catalyze. In particular, phospholipase A<sub>1</sub> (PLA<sub>1</sub>) specifically catalyzes the cleavage at the sn-1 position of phospholipids, forming a fatty acid and a lysophospholipid.
PLA<sub>1</sub>'s are present in numerous species including humans, and have a variety of cellular functions that include regulation and facilitation of the production of lysophospholipid mediators, and acting as digestive enzymes. These enzymes are responsible for fast turnover rates of cellular phospholipids. In addition to this, the products of the reaction catalyzed by PLA<sub>1</sub> which are a fatty acid and a lysophospholipid are important in various biological functions such as platelet aggregation and smooth muscle contraction. In addition, lysophospholipids can be found as surfactants in food techniques and cosmetics, and can be used in drug delivery. Since PLA<sub>1</sub> is found in many species, it has been found that there are different classes of this one specific enzyme based on the organism being studied.
There are many variations of PLA<sub>1</sub>, differing slightly between each organism it is present in. Most notably, it can be found in mammalian cells such as plasma of rat livers and bovine brains, and can also be found in metazoan parasites, protozoan parasites, and snake venom.
Optimum pH conditions for PLA<sub>1</sub> activity on neutral phospholipids is around 7.5, whereas the optimal conditions for PLA<sub>1</sub> activity on acidic phospholipids is around 4.
The structure of a PLA<sub>1</sub> is a monomer that contains the following sequence: Gly-X-Ser-X-Gly, where X represents any other amino acid. The serine is considered the active site in the enzyme. PLA<sub>1</sub>'s also contain a catalytic triad of Ser-Asp-His, with a variety of cysteine residues needed for disulfide bond formation. The cysteine residues are responsible for key structural motifs such as the lid domain and the B9 domain, both of which are lipid binding surface loops. These two loops can vary between each PLA<sub>1</sub>. For example, a PLA<sub>1</sub> enzyme with a long lid domain (22-23 amino acids) and a long B9 domain (18-19 amino acids) constitute an extracellular PLA<sub>1</sub> exhibiting triacylglycerol hydrolase activity. In contrast, a PLA<sub>1</sub> enzyme that is considered more selective will have a short lid and B9 domain that span 7-12 and 12-13 amino acids, respectively.
Unlike other phospholipases such as PLA<sub>2</sub>, there is much that is unknown about PLA<sub>1</sub> due to the lack of any efficient way to purify, clone, express, and characterize this enzyme. PLA<sub>1</sub> is currently commercially unavailable because of this. Lysophospholipids can be found as surfactants in food techniques and cosmetics, and can be used in drug delivery. Current research is being applied to determine suitable growth environments for PLA<sub>1</sub> production. In one particular study, it was found that PLA<sub>1</sub> can be produced by S. cerevisiae and A. oryzae. In these PLA<sub>1</sub> producing cultures, increasing the nitrogen and carbon sources can lead to increase in PLA<sub>1</sub> yields.
In the early 1900s, an observation was made, showing an accumulation of free fatty acids after incubation of pancreatic juice with phosphatidylcholine. One of the first cases of observed PLA<sub>1</sub> activity was on 1903 when snake venom was found to alter phosphatidylcholine into lysophosphatidylcholine, which is defined as a phosphatidylcholine without one of its fatty acids. In the 1960s, it was discovered to be that enzymes catalyze this fatty acid cleavage in multiple ways, one of which is the sn-1 position. This particular reaction is catalyzed by PLA<sub>1</sub>, while the reaction at the sn-2 position is catalyzed by phospholipase A2.