Phospholipase

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Phospholipase cleavage sites. An enzyme that displays both PLA1 and PLA2 activities is called a Phospholipase B. Phospholipases2.png
Phospholipase cleavage sites. An enzyme that displays both PLA1 and PLA2 activities is called a Phospholipase B .

A phospholipase is an enzyme that hydrolyzes phospholipids [1] into fatty acids and other lipophilic substances. Acids trigger the release of bound calcium from cellular stores and the consequent increase in free cytosolic Ca2+, an essential step in calcium signaling to regulate intracellular processes. [2] There are four major classes, termed A, B, C, and D, which are distinguished by the type of reaction which they catalyze:

Contents

Types C and D are considered phosphodiesterases.

Endothelial lipase is primarily a phospholipase. [3]

Phospholipase A2 acts on the intact lecithin molecule and hydrolyzes the fatty acid esterified to the second carbon atom. The resulting products are lysolecithin and a fatty acid. Phospholipase A2 is an enzyme present in the venom of bees, blennies and viper snakes. [4]

See also

Related Research Articles

Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processes that generate energy and (2) anabolic processes where they serve as building blocks for other compounds.

Phosphatidic acids are anionic phospholipids important to cell signaling and direct activation of lipid-gated ion channels. Hydrolysis of phosphatidic acid gives rise to one molecule each of glycerol and phosphoric acid and two molecules of fatty acids. They constitute about 0.25% of phospholipids in the bilayer.

Phospholipase A2 Peripheral membrane protein

Phospholipases A2 (PLA2s) EC 3.1.1.4 are enzymes that cleave fatty acid in position two of phospholipids, hydrolyzing the bond between the second fatty acid “tail” and the glycerol molecule. This particular phospholipase specifically recognizes the sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond, releasing arachidonic acid and lysophosphatidic acid. Upon downstream modification by cyclooxygenases or lipoxygenases, arachidonic acid is modified into active compounds called eicosanoids. Eicosanoids include prostaglandins and leukotrienes, which are categorized as anti-inflammatory and inflammatory mediators.

Glycerophospholipid

Glycerophospholipids or phosphoglycerides are glycerol-based phospholipids. They are the main component of biological membranes.

Lingual lipase

Lingual lipase is a member of a family of digestive enzymes called triacylglycerol lipases, EC 3.1.1.3, that use the catalytic triad of aspartate, histidine, and serine to hydrolyze medium and long-chain triglycerides into partial glycerides and free fatty acids. The enzyme, released into the mouth along with the saliva, catalyzes the first reaction in the digestion of dietary lipid, with diglycerides being the primary reaction product. However, due to the unique characteristics of lingual lipase, including a pH optimum 4.5–5.4 and its ability to catalyze reactions without bile salts, the lipolytic activity continues through to the stomach. Enzyme release is signaled by autonomic nervous system after ingestion, at which time the serous glands under the circumvallate and foliate lingual papillae on the surface of the tongue secrete lingual lipase to the grooves of the circumvallate and foliate papillae, co-localized with fat taste receptors. The hydrolysis of the dietary fats is essential for fat absorption by the small intestine, as long chain triacylglycerides cannot be absorbed, and as much as 30% of fat is hydrolyzed within 1 to 20 minutes of ingestion by lingual lipase alone.

Lipid signaling

Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. Lipid signaling is thought to be qualitatively different from other classical signaling paradigms because lipids can freely diffuse through membranes. One consequence of this is that lipid messengers cannot be stored in vesicles prior to release and so are often biosynthesized "on demand" at their intended site of action. As such, many lipid signaling molecules cannot circulate freely in solution but, rather, exist bound to special carrier proteins in serum.

Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown or storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. In animals, these fats are obtained from food or are synthesized by the liver. Lipogenesis is the process of synthesizing these fats. The majority of lipids found in the human body from ingesting food are triglycerides and cholesterol. Other types of lipids found in the body are fatty acids and membrane lipids. Lipid metabolism is often considered as the digestion and absorption process of dietary fat; however, there are two sources of fats that organisms can use to obtain energy: from consumed dietary fats and from stored fat. Vertebrates use both sources of fat to produce energy for organs such as the heart to function. Since lipids are hydrophobic molecules, they need to be solubilized before their metabolism can begin. Lipid metabolism often begins with hydrolysis, which occurs with the help of various enzymes in the digestive system. Lipid metabolism also occurs in plants, though the processes differ in some ways when compared to animals. The second step after the hydrolysis is the absorption of the fatty acids into the epithelial cells of the intestinal wall. In the epithelial cells, fatty acids are packaged and transported to the rest of the body.

Long-chain-fatty-acid—CoA ligase

The long chain fatty acyl-CoA ligase is an enzyme of the ligase family that activates the oxidation of complex fatty acids. Long chain fatty acyl-CoA synthetase catalyzes the formation of fatty acyl-CoA by a two-step process proceeding through an adenylated intermediate. The enzyme catalyzes the following reaction,

Phospholipase A1

Phospholipase A1 encoded by the PLA1A gene is a phospholipase enzyme which removes the 1-acyl. Phospholipase A1 is an enzyme that resides in a class of enzymes called phospholipase that hydrolyze phospholipids into fatty acids. There are 4 classes, which are separated by 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.

Serine hydrolases are one of the largest known enzyme classes comprising approximately ~200 enzymes or 1% of the genes in the human proteome. A defining characteristic of these enzymes is the presence of a nucleophilic serine in their active site, which is used for the hydrolysis of substrates. Catalysis proceeds by the formation of an acyl-enzyme intermediate through this serine, followed by water/hydroxide-induced saponification of the intermediate and regeneration of the enzyme. Unlike other non-catalytic serines, the nucleophilic serine of these hydrolases is typically activated by a proton relay involving a catalytic triad consisting of the serine, an acidic residue and a basic residue, although variations on this mechanism exist.

The lysophospholipid receptor (LPL-R) group are members of the G protein-coupled receptor family of integral membrane proteins that are important for lipid signaling. In humans, there are eight LPL receptors, each encoded by a separate gene. These LPL receptor genes are also sometimes referred to as "Edg".

Endothelial lipase (LIPG) is a form of lipase secreted by vascular endothelial cells in tissues with high metabolic rates and vascularization, such as the liver, lung, kidney, and thyroid gland. The LIPG enzyme is a vital component to many biological process. These processes include lipoprotein metabolism, cytokine expression, and lipid composition in cells. Unlike the lipases that hydrolyze Triglycerides, endothelial lipase primarily hydrolyzes phospholipids. Due to the hydrolysis specificity, endothelial lipase contributes to multiple vital systems within the body. On the contrary to the beneficial roles that LIPG plays within the body, endothelial lipase is thought of to play a potential role in cancer and inflammation. Knowledge obtained in vitro and in vivo suggest the relations to these conditions, but human interaction knowledge lacks due to the recent discovery of endothelial lipase. Endothelial lipase was first characterized in 1999. The two independent research groups which are notable for this discovery cloned the endothelial lipase gene and identified the novel lipase secreted from endothelial cells. The anti-Atherosclerosis opportunity through alleviating plaque blockage and prospective ability to raise High-density lipoprotein (HDL) have gained endothelial lipase recognition.

In enzymology, a glycosylphosphatidylinositol diacylglycerol-lyase is an enzyme that catalyzes the chemical reaction

Phospholipase C Class of enzymes

Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role in eukaryotic cell physiology, in particular signal transduction pathways. Phospholipase C's role in signal transduction is its cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), which serve as second messengers. Activators of each PLC vary, but typically include heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca2+, and phospholipids.

N-Acylphosphatidylethanolamines (NAPEs) are hormones released by the small intestine into the bloodstream when it processes fat. NAPEs travel to the hypothalamus in the brain and suppress appetite. This mechanism could be relevant for treating obesity.

N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) is an enzyme that catalyzes the release of N-acylethanolamine (NAE) from N-acyl-phosphatidylethanolamine (NAPE). This is a major part of the process that converts ordinary lipids into chemical signals like anandamide and oleoylethanolamine. In humans, the NAPE-PLD protein is encoded by the NAPEPLD gene.

Lipase Class of enzymes

A lipase are a family of enzymes that catalyzes the hydrolysis of fats. Some lipases display broad substrate scope including esters of cholesterol, phospholipids, and of lipid-soluble vitamins. and sphingomyelinases; however, these are usually treated separately from "conventional" lipases. Unlike esterases, which function in water, lipases "are activated only when adsorbed to an oil–water interface". Lipases perform essential roles in digestion, transport and processing of dietary lipids in most, if not all, organisms.

1-Lysophosphatidylcholine

2-acyl-sn-glycero-3-phosphocholines are a class of phospholipids that are intermediates in the metabolism of lipids. Because they result from the hydrolysis of an acyl group from the sn-1 position of phosphatidylcholine, they are also called 1-lysophosphatidylcholine. The synthesis of phosphatidylcholines with specific fatty acids occurs through the synthesis of 1-lysoPC. The formation of various other lipids generates 1-lysoPC as a by-product.

N-acetylphosphatidylethanolamine-hydrolysing phospholipase D (EC 3.1.4.54, NAPE-PLD, anandamide-generating phospholipase D, N-acyl phosphatidylethanolamine phospholipase D, NAPE-hydrolyzing phospholipase D) is an enzyme with systematic name N-acetylphosphatidylethanolamine phosphatidohydrolase. This enzyme catalyses the following chemical reaction

Discovery and development of gastrointestinal lipase inhibitors

Lipase inhibitors belong to a drug class that is used as an antiobesity agent. Their mode of action is to inhibit gastric and pancreatic lipases, enzymes that play an important role in the digestion of dietary fat. Lipase inhibitors are classified in the ATC-classification system as A08AB . Numerous compounds have been either isolated from nature, semi-synthesized, or fully synthesized and then screened for their lipase inhibitory activity but the only lipase inhibitor on the market is orlistat . Lipase inhibitors have also shown anticancer activity, by inhibiting fatty acid synthase.

References

  1. " phospholipase " at Dorland's Medical Dictionary
  2. Molinari, Giuliano; Nervo, Elsa (2021-02-26). "Role of protons in calcium signaling". The Biochemical Journal. 478 (4): 895–910. doi:10.1042/BCJ20200971. ISSN   1470-8728. PMID   33635336.
  3. Yu JE, Han SY, Wolfson B, Zhou Q (2018). "The role of endothelial lipase in lipid metabolism, inflammation, and cancer". Histology and Histopathology . 33 (1): 1–10. doi:10.14670/HH-11-905. PMC   5858721 . PMID   28540715.
  4. D. M. Vasudevan & S. Sreekumari, Textbook of Biochemistry (5th ed.)

Further reading