Lipoprotein Lipase an overview

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Lipoprotein Lipase
Lipoprotein lipase (LPL) is the key enzyme that acts
on the endothelial surface of extrahepatic
capillaries, releasing large amounts of fatty acids
from these lipoproteins for the uptake by cells of
neighboring tissues for production or storage of
energy [156].
From: 
Advances in Clinical Chemistry, 2019
Related terms:
Low-Density Lipoprotein
, 
Triglyceride
, 
Lipoprotein
,
Very Low-Density Lipoprotein
, 
Chylomicron
, 
Lipase
, 
Tissues
, 
Lipids
, 
Fatty Acids
, 
Adipose Tissue
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Biochemistry of Lipids,
Lipoproteins and Membranes
Phoebe E. Fielding, Christopher J. Fielding, in
New Comprehensive Biochemistry
, 1996
2.3 Synthesis, regulation and transport of
LPL to its endothelial site
LPL is synthesized mainly in the parenchymal cells
of smooth muscle and adipose tissue. Heparin
perfusion, which displaces LPL from its
proteoglycan binding site on the capillary
endothelial surface, abolishes the ability of these
tissues to clear fatty acids from chylomicrons and
VLDLs. The functional pool of LPL must therefore be
that located at the vascular surface of endothelial
cells in both muscle and adipose tissues.
The rate of synthesis of LPL, and its activity at the
capillary endothelial surface, change several-fold as
demand for fatty acid for oxidative metabolism is
modified. Multiple signals regulate the
transcription of the LPL gene in the adipocyte [3].
Many of these signals are mediated via protein
kinase C, which activates the c-fos (possibly also the
c-jun)
protooncogenes, whose products bind to the
adipose regulatory element FRE-2 (Fig. 3). This
complex then interacts with LPL promoter
sequences. There is also feedback regulation of the
rate of new LPL synthesis by LPL outside the
adipocyte. Uptake of LPL by the adipocyte
stimulates protein kinase C to increase tumor
necrosis factor production, which in turn reduces
LPL synthesis and secretion. Little is known of the
regulation of myocyte LPL transcription or
translation.
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Fig. 3. Synthesis, secretion and transport of LPL from the adipocyte to
the vascular endothelial surface.
A heparin-releasable, LPL-binding protein (HRP-
116) is present on the adipocyte surface (Fig. 3). LPL
secreted from adipocytes may be transported
through the intercellular space to the capillary
endothelium as a complex with this protein [4]. The
complex could be taken up intact by the endothelial
cell; or free LPL might be internalized following its
dissociation at the basal face of the endothelial cell.
Transendothelial movement of LPL probably utilizes
transport vesicles similar to those identified in the
transfer of other proteins, but cellular
intermediates of this process have not yet been
isolated.
LPL is bound to the endothelial vascular surface via
a 220 kDa proteoglycan whose functional site is
probably a highly sulfated decasaccharide [5]. Small
amounts of soluble LPL are recovered in the plasma
when plasma triacylglycerol levels are very high. It
is not clear that this represents a significant
mechanism of regulation or recycling.
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Volume 2
Yonghua Wang, Dongxiao Sun-Waterhouse, in
Encyclopedia of Food Chemistry
, 2019
Translocation of LPL
LPL has been thought to bind to the HSPGs on the
luminal surface of the endothelial cells where the
hydrolysis of TAG-rich lipoproteins normally takes
place (Obunike et al., 2001). Recent studies
indicated that the role of a
glycosylphosphatidylinositol-anchored protein
named “glycosylphosphatidylinositol-anchored
high-density lipoprotein–binding protein 1”
(GPIHBP1) as the binding site for LPL in the
capillary lumen, a “platform for lipolysis”, should
also deserve attention (Meneghetti et al., 2015). The
exact mechanism of LPL transport remains unclear,
although transcytosis of LPL across endothelial cells
involving parenchymal heparan sulfate-
proteoglycans (HSPGs) and the VLDL receptor has
been believed the characteristic process. LPL can be
released from the parenchymal HSPGs via the
catalysis by the heparanase from the endothelial
cells, which may either enter the circulation or bind
to the oligosaccharides and transport to the
endothelial cells due to the polarity of endothelial
cells. The endothelial cells release two forms of
heparanase: active and the latent form. The active
form releases LPL from the myocyte surface whilst
the latent form stimulates intracellular LPL through
RhoA activation mediated by HSPGs (Li et al., 2014).
Sub-endothelial matrix isolates and stabilizes the
LPL, Fig. 1 summarizes the synthesis, activation,
secretion, and translocation of LPL.
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Figure 1. A diagram representing the synthesis, activation, secretion,
and translocation of LPL. After synthesis and activation in the ER, LPL
enters the Golgi apparatus where it is either secreted or undergo
lysosomal degradation following which LPL binds to the HSPGs and
translocated to the abluminal side of endothelial cells. Finally, LPL is
transported to the luminal surface via transcytosis process where it
carries out hydrolysis with the help of GPIHBP1.
Adapted from Li et al. (2014).
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Diacylglycerol Lipase (DAG Lipase)
Steve P.H. Alexander, in
xPharm: The Comprehensive Pharmacology Reference
,
2009
Introduction
Diacylglycerol lipase (DAG lipase) has two
identifiable functions. First, DAG lipase has a
metabolic function to hydrolyze lipids. Second, DAG
lipase has the capacity to generate 2-
arachidonoylglycerol (2AG), arguably THE
endogenous cannabinoid receptor agonist. The
diacylglycerol substrate for DAG lipase is
presumably produced through the action of
phospholipase C on the membrane phospholipid
phosphatidylinositol 4,5-bisphosphate (PIP ).
There has been considerable interest in identifying
the localization, ontogeny and regulation of DAG
lipase as a means of gaining greater insight into the
turnover and function of endocannabinoids. Two
isoforms (α and β) were cloned in 2003 after
searching the human genome for sequences related
to the DAG lipase from Penicillium Bisogno et al
(2003). Neither isoform appears to express
significant monoacylglycerol lipase, phospholipase
A /A , triacylglycerol lipase or fatty acid amide
hydrolase activity Bisogno et al (2003).
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Apolipoprotein B-48
Katsuyuki Nakajima, ... Ernst Schaefer, in
Advances in Clinical Chemistry
, 2014
14.4 LPL gene therapy
LPL is one of the key enzymes in TRL metabolism,
especially apoB-48 containing CM particles. LPL is
produced in fat, skeletal, and heart muscle.
Activated by its cofactor apoC-II [198], LPL mediates
the hydrolysis of TG in CM and VLDL at the luminal
side of the endothelium. Generated FFA are
subsequently used for energy production in muscle
or stored as fat in adipose. LPL also contributes to
the HDL pool by shedding of phospholipids and
apolipoproteins during lipoprotein hydrolysis [199].
Besides its enzymatic activity, LPL also enhances
hepatic clearance of TRL by facilitating receptor-
mediated uptake of atherogenic lipoprotein