**2.6 Endothelial lipase**

274 New Advances in the Basic and Clinical Gastroenterology

PLA1 catalyzes the hydrolysis of fatty acids exclusively at the sn-1 position of phospholipids. A free fatty acid (FFA) and a lysophospholipid (lysoPL) are the products of this reaction. However, this class of phospholipase is not well understood, and no crystal structures exist. The assignment of a function for this pancreatic enzyme has yet to be firmly

In intraluminal digestion, phospholipase A2 is primarily responsible for hydrolyzing phosphatidyl-choline to 2-lysophophatidyl-choline. This reaction is important in triglyceride digestion as the amphipathic phosphatidyl-choline, in a manner similar to bile salts, will adsorb to the surface of the lipid droplets, preventing contact between the lipase-colipase complex and its lipid substrate. Hydrolysis of phosphatidyl-choline by phospholipase 2 will allow desorption of lysophosphatidyl-choline, which is water soluble. The subsequent mucosal absorption of lysophosphatidyl-choline is important in the generation of enterocyte phospholipids and lipoproteins and, thus, chylomicron formation (Nouri-Sorkhabi & al.,

As the name suggests, hepatic lipase (EC 3.1.1.3) is synthesized mostly by hepatocytes in the liver and found localized at the surface of liver sinusoidal capillaries (Perret & al., 2002). The human hepatic lipase presents four glycosylation sites, which are localized at positions 20, 56, 340, and 375, and a molecular mass around 65 kDa (Ben-Zeev & al., 1994 ; Wolle & al., 1993). Together with lipoprotein lipase (LPL), hepatic lipase (HL) could be considered as a lipase of the vascular compartment (Perret & al., 2002). Unlike pancreatic lipase, hepatic lipase does not require a cofactor for its activity; is stable at high salt concentrations and is inactivated by sodium dodecyl sulfate (Mukherjee, 2003). HL exerts both triglyceride lipase and phospholipase A1 activities, and is involved at different steps of lipoprotein metabolism (Santamarina-Fojo & al., 2004). The preferred physiological substrate of hepatic lipase is triglyceride of intermediate density lipoprotein (IDL) particle, which it hydrolyses to form triglyceride-poor and cholesterol-rich low-density lipoprotein (LDL). Hepatic lipase also converts post-prandial triglyceride rich high-density lipoprotein (HDL) particle (i.e.HDL2)

Lipoprotein lipase (EC 3.1.1.34) (LPL) is a non-covalent homodimeric protein produced mainly by the adipose, heart and muscle tissue and to some extent by macrophages (Camp & al., 1990). LPL is secreted from parenchymal cells as a glycosylated homodimer, after which it is translocated through the extracellular matrix and across endothelial cells to the capillary lumen. After secretion, however, the mechanism by which LPL travels across endothelial cells is still unknown (Braun & Severeson 1992; Mead & al., 2002). The glycosylation sites of LPL are Asn-43, Asn-257, and Asn-359 (Mead & al., 2002). Lipoprotein lipase has multiple functional domains including lipid-binding, the dimer formation, heparin binding, cofactor interaction and fatty acid-binding domains (Santamarina-Fojo & Dugi, 1994). Interaction of the enzyme with the lipoprotein substrate takes place in the lipidbinding domain. This results in a conformational change that leads to the movement of a short helical segment or 'lid' to expose the active site containing the Ser-Asp-His catalytic triad, where hydrolysis of triacylglycerol takes place (Emmerich & al., 1992). As a

to post-absorptive triglyceride poor HDL (i.e. HDL3) (Mukherjee, 2003).

established (Richmond & Smith, 2011).

2000).

**2.4 Hepatic lipase** 

**2.5 Lipoprotein lipase** 

Endothelial lipase (EC 3.1.1.3) which was firstly characterized in 1999 was also added to the lipase gene family (Jaye & al., 1999). Mature endothelial lipase is a 68 kDa glycoprotein with five potential N-linked glycosylation sites (Yasuda & al., 2010). It has 44% primary sequence homology with lipoprotein lipase, 41% with hepatic lipase and 27% with pancreatic lipase (Choi & al., 2002). The enzyme is secreted by endothelial cells from various tissues like lung, liver, kidney and placenta. However, heart and skeletal muscles do not express endothelial lipase (Jaye & al., 1999). Endothelial lipase differs from the other enzymes of the lipase gene family in the sequence of the 'lid' domain. Its 19-residue 'lid' region is 3 residues shorter and less amphipathic than 'lid' region of lipoprotein or hepatic lipase indicating a different enzymatic function (Jaye & al., 1999). Indeed, unlike lipoprotein or hepatic lipases that have triacylglycerol lipase activity, endothelial lipase has primarily a phospholipase A1 activity. It was suggested that endothelial lipase plays a physiologic role in HDL metabolism probably by catalyzing hydrolysis of HDL phospholipids thereby facilitating a direct HDL receptormediated uptake (Cohen, 2003). Endothelial lipase may also facilitate the uptake of apolipoprotein B-containing remnant lipoprotein. As the placental tissue abundantly expresses endothelial lipase, it may also have a role in the development of fetus (Choi & al., 2002).
