Phospholipase A1

Crystallographic structure of phospholipase A1. Red region denotes α helices, Green region denotes loops, and yellow region denotes β sheets.
Identifiers
EC no.	3.1.1.32
CAS no.	9043-29-2
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

phospholipase A1 member A
Identifiers
Symbol	PLA1A
NCBI gene	51365
HGNC	17661
OMIM	607460
RefSeq	NM_015900
UniProt	Q53H76
Other data
EC number	3.1.1.32
Locus	Chr. 3 q13.13-13.2
Search for Structures Swiss-model Domains InterPro

Phospholipase A₁ (EC 3.1.1.32; systematic name: phosphatidylcholine 1-acylhydrolase) encoded by the PLA₁A gene is a phospholipase enzyme which removes the 1-acyl group: ^[1]

phosphatidylcholine + H₂O ⇌ 2-acylglycerophosphocholine + a carboxylate

It is an enzyme that resides in a class of enzymes called phospholipase that hydrolyze phospholipids into fatty acids. ^[2] There are four classes, separated according to the type of reaction they catalyze. In particular, phospholipase A₁ (PLA₁) specifically catalyzes the cleavage at the sn-1 position of phospholipids, forming a fatty acid and a lysophospholipid. ^{[3] [4]}

Phospholipase A₁ cleaves phospholipid at the sn-1 position forming a lysophospholipid and a fatty acid.

Function

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. ^[5] 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. ^[6] In addition, lysophospholipids can be found as surfactants in food techniques and cosmetics, and can be used in drug delivery. ^[7] 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. ^{[8] [9]}

Species and tissue distribution

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.

Substrate specificity

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. ^{[10] [11]}

Structure

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. ^[12] 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. ^[13] 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.

Industrial use

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. ^[13] 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. ^[8]

Discovery

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.

See also

• Outer membrane phospholipase A1

References

1. Phospholipase+A1 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
2. DeSilva NS, Quinn PA (1999). "Characterization of phospholipase A₁, A₂, C activity in Ureaplasma urealyticum membranes". Mol. Cell. Biochem. 201 (1–2): 159–67. doi:10.1023/A:1007082507407. PMID   10630635. S2CID   22101516.
3. Richmond GS, Smith TK (2011). "Phospholipases A₁". International Journal of Molecular Sciences. 12 (1): 588–612. doi: 10.3390/ijms12010588 . PMC   3039968 . PMID   21340002.
4. Scandella CJ, Kornberg A (November 1971). "A membrane-bound phospholipase A₁ purified from Escherichia coli". Biochemistry. 10 (24): 4447–56. doi:10.1021/bi00800a015. PMID   4946924.
5. Franson R, Waite M, LaVia M (May 1971). "Identification of phospholipase A₁ and A₂ in the soluble fraction of rat liver lysosomes". Biochemistry. 10 (10): 1942–6. doi:10.1021/bi00786a031. PMID   4397924.
6. Inoue K, Arai H, Aoki J (2004). "Phospholipase A₁ Structures, Physiological and Patho-physiological Roles in Mammals". In Müller G, Petry S (eds.). Lipases and phospholipases in drug development : from biochemistry to molecular pharmacology . Weinheim: Wiley-VCH. p.  23. doi:10.1002/3527601910.ch2. ISBN   9783527306770.
7. Pichon R (Jun 1975). "[Recent acquisitions on the treatment of perinatal infections]". Maroc Med. 55 (591): 280–5. PMID   1177510.
8. Shiba Y, Ono C, Fukui F, Watanabe I, Serizawa N, Gomi K, Yoshikawa H (Jan 2001). "High-level secretory production of phospholipase A₁ by Saccharomyces cerevisiae and Aspergillus oryzae". Biosci Biotechnol Biochem. 65 (1): 94–101. doi: 10.1271/bbb.65.94 . PMID   11272851.
9. Imae R, Inoue T, Kimura M, Kanamori T, Tomioka NH, Kage-Nakadai E, Mitani S, Arai H (Sep 2010). "Intracellular phospholipase A₁ and acyltransferase, which are involved in Caenorhabditis elegans stem cell divisions, determine the sn-1 fatty acyl chain of phosphatidylinositol". Mol Biol Cell. 21 (18): 3114–24. doi:10.1091/mbc.E10-03-0195. PMC   2938378 . PMID   20668164.
10. Mebarek S, Abousalham A, Magne D, Do le D, Bandorowicz-Pikula J, Pikula S, Buchet R (2013). "Phospholipases of Mineralization Competent Cells and Matrix Vesicles: Roles in Physiological and Pathological Mineralizations". International Journal of Molecular Sciences. 14 (3): 5036–129. doi: 10.3390/ijms14035036 . PMC   3634480 . PMID   23455471.
11. Nishijima M, Akamatsu Y, Nojima S (Sep 1974). "Purification and properties of a membrane-bound phospholipase A₁ from Mycobacterium phlei". J Biol Chem. 249 (17): 5658–67. doi: 10.1016/S0021-9258(20)79778-4 . PMID   4415399.
12. Aoki J, Inoue A, Makide K, Saiki N, Arai H (2007). "Structure and function of extracellular phospholipase A₁ belonging to the pancreatic lipase gene family". Biochimie. 89 (2): 197–204. doi:10.1016/j.biochi.2006.09.021. PMID   17101204.
13. Aoki J, Nagai Y, Hosono H, Inoue K, Arai H (May 2002). "Structure and function of phosphatidylserine-specific phospholipase A₁". Biochim Biophys Acta. 1582 (1–3): 26–32. doi:10.1016/s1388-1981(02)00134-8. PMID   12069807.