About Secreted Phospholipases A2 / sPLA2:
Also known as sPLA2s, secreted phospholipases A2 are enzymes that hydrolize the bond between the glycerol molecule and the second fatty acid tail by cleaving the fatty acid in position two of phospholipids.
Secreted phospholipases have an Enzyme Commission (EC) number of 220.127.116.11 and a CAS Number of 9001-84-7. Secreted phospholipases are a distinct family within the larger phospholipases A2 PLA2 family.
SPLA2 enzymes act on phospholipids of varying aggregates including monolayer, micellar, and bilayer phospholipid in relation to their type, which could be zwitterionic, anionic, neutral, fatty acid composition, or biological milieu. The catalytic efficiency is primarily determined by the packing density, phase transition temperature, critical micellar concentration, and other physical properties of the aggregates.
The PLA2 family is composes of sPLA2s and intracellular PLA2s. The sPLA2s were the first of the wider PLA2 family to be discovered, being located in snake, scorpion, bee, and wasp venoms. Other structural characteristics include a low modular weight, histidine I the catalytic site, and the need for Ca2 to activate. Secreted PLA2s usually show an an increase in activity termed interfacial activation when substrate is presented as a large lipid aggregate too.
Secreted Phospholipases A2 Function & Mechanisms
Pancreatic sPLA2s produce the initial digestion of phospholipid compounds in dietary fat, making it a key feature in immobilizing prey through cell lysis (the breaking down of the cell). Studies have shown a function of sPLA2s in sperm maturation and capacitation.
Secreted phospholipases A2 additionally promote inflammation by breaking down phospholipids, which then produces fatty acids and arachidonic acid. Once metabolized, it can form inflammatory and thrombogenic molecules, which is why excess levels can contribute to various related diseases. It is also closely linked to coronary artery disease and acute coronary syndrome. Excess levels of sPLA2 may also increase asthma in children as well as dry eye surface inflammation.
SPAL2 degradation of supporting phospholipid bilayers are met by a latency period, otherwise known as a lag phase, in which low enzyme activity and the lack of hydrolysis are evident. The lag phase is influenced by the molecular structure. Increased secreted phospholipases A2 is also noted in Alzheimer's patients as well as those with multiple sclerosis.
Pancreatic sPLA2 is initiated by a His-48/Asp-99/calcium complex, resulting in a catalyric mechanism within the active site. Once the calcium ion polarizes the sn-2 carbonyl oxygen and interacts with the w5 water molecule nucleophilicity of the catalytic water levels are improved by the w6 water module.
The expression of secreted phospholipases A2 is also influenced by interactions with proinflammatory stimuli such as LPS, IL-1β, and IFN-γ. It can impact the assessment of physiological functions relating to PLA2G2A while a frameshift mutation can mean that it is not expressed at all – or expressed in a highly restricted fashion.
Properties of the sPLA2 family signify an importance in antibacterial defense due to low hydrlyziation, as well as the impact it has on inflammation and the risks (including the development of cancer) that chronic inflammation can bring.