Phospholipase A1

PLA₁'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.{{cite journal |vauthors=Franson R, Waite M, LaVia M | title = Identification of phospholipase A₁ and A₂ in the soluble fraction of rat liver lysosomes | journal = Biochemistry | volume = 10 | issue = 10 | pages = 1942–6 |date=May 1971 | pmid = 4397924 | doi = 10.1021/bi00786a031 }} In addition to this, the products of the reaction catalyzed by PLA₁ which are a fatty acid and a lysophospholipid are important in various biological functions such as platelet aggregation and smooth muscle contraction.{{cite book |veditors=Müller G, Petry S | title = Lipases and phospholipases in drug development : from biochemistry to molecular pharmacology |url=https://archive.org/details/lipasesphospholi00mlle |url-access=limited | year = 2004 | publisher = Wiley-VCH | location = Weinheim | isbn = 9783527306770 | chapter = Phospholipase A₁ Structures, Physiological and Patho-physiological Roles in Mammals |vauthors=Inoue K, Arai H, Aoki J | page = [https://archive.org/details/lipasesphospholi00mlle/page/n43 23] | doi = 10.1002/3527601910.ch2 }} In addition, lysophospholipids can be found as surfactants in food techniques and cosmetics, and can be used in drug delivery.{{cite journal | author = Pichon R | title = [Recent acquisitions on the treatment of perinatal infections]. | journal = Maroc Med | volume = 55 | issue = 591 | pages = 280–5 | date = Jun 1975 | pmid = 1177510 }} Since PLA₁ 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.{{cite journal |vauthors=Imae R, Inoue T, Kimura M, Kanamori T, Tomioka NH, Kage-Nakadai E, Mitani S, Arai H | title = Intracellular phospholipase A₁ and acyltransferase, which are involved in Caenorhabditis elegans stem cell divisions, determine the sn-1 fatty acyl chain of phosphatidylinositol. | journal = Mol Biol Cell | volume = 21 | issue = 18 | pages = 3114–24 | date = Sep 2010 | pmid = 20668164 | pmc = 2938378 | doi = 10.1091/mbc.E10-03-0195 }}

There are many variations of PLA₁, 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 PLA₁ activity on neutral phospholipids is around 7.5, whereas the optimal conditions for PLA₁ activity on acidic phospholipids is around 4.{{cite journal |vauthors=Mebarek S, Abousalham A, Magne D, Do le D, Bandorowicz-Pikula J, Pikula S, Buchet R | title = Phospholipases of Mineralization Competent Cells and Matrix Vesicles: Roles in Physiological and Pathological Mineralizations | journal = International Journal of Molecular Sciences | volume = 14 | issue = 3 | pages = 5036–129 | year = 2013 | pmid = 23455471 | doi = 10.3390/ijms14035036 | pmc=3634480| doi-access = free }}{{cite journal |vauthors=Nishijima M, Akamatsu Y, Nojima S | title = Purification and properties of a membrane-bound phospholipase A₁ from Mycobacterium phlei. | journal = J Biol Chem | volume = 249 | issue = 17 | pages = 5658–67 | date = Sep 1974 | doi = 10.1016/S0021-9258(20)79778-4 | pmid = 4415399 | doi-access = free }}

The structure of a PLA₁ 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.{{cite journal |vauthors=Aoki J, Inoue A, Makide K, Saiki N, Arai H | title = Structure and function of extracellular phospholipase A₁ belonging to the pancreatic lipase gene family | journal = Biochimie | volume = 89 | issue = 2 | pages = 197–204 | year = 2007 | pmid = 17101204 | doi = 10.1016/j.biochi.2006.09.021 }} PLA₁'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 PLA₁. For example, a PLA₁ enzyme with a long lid domain (22-23 amino acids) and a long B9 domain (18-19 amino acids) constitute an extracellular PLA₁ exhibiting triacylglycerol hydrolase activity.{{cite journal |vauthors=Aoki J, Nagai Y, Hosono H, Inoue K, Arai H | title = Structure and function of phosphatidylserine-specific phospholipase A₁ | journal = Biochim Biophys Acta | volume = 1582 | issue = 1–3 | pages = 26–32 | date = May 2002 | pmid = 12069807 | doi = 10.1016/s1388-1981(02)00134-8 }} In contrast, a PLA₁ 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 PLA₂, there is much that is unknown about PLA₁ due to the lack of any efficient way to purify, clone, express, and characterize this enzyme. PLA₁ 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 PLA₁ production. In one particular study, it was found that PLA₁ can be produced by S. cerevisiae and A. oryzae. In these PLA₁ producing cultures, increasing the nitrogen and carbon sources can lead to increase in PLA₁ yields.{{cite journal |vauthors=Shiba Y, Ono C, Fukui F, Watanabe I, Serizawa N, Gomi K, Yoshikawa H | title = High-level secretory production of phospholipase A₁ by Saccharomyces cerevisiae and Aspergillus oryzae. | journal = Biosci Biotechnol Biochem | volume = 65 | issue = 1 | pages = 94–101 | date = Jan 2001 | pmid = 11272851 | doi = 10.1271/bbb.65.94 | doi-access = free }}

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 PLA₁ 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 PLA₁, while the reaction at the sn-2 position is catalyzed by phospholipase A2.

• Outer membrane phospholipase A1

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Category:Peripheral membrane proteins

Category:EC 3.1.1