Lipoprotein lipase functions

ApoC-I is expressed mainly in liver but also in lung, skin, testis, spleen, neural retina, and RPE. Its multiple functions include the activation of lecithin cholesterol acyltransferase (LCAT) and the inhibition, among others, of lipoprotein and hepatic lipases that hydrolyze triglycerides in particle cores. Notably, both LCAT and lipoprotein lipases are expressed in RPE and choroid (Li et al., 2006). Moreover ApoC-I has been shown to displace ApoE on the VLDL and LDL and thus hinder their binding and uptake via their corresponding receptors (Li et al., 2006). 

ApoC-II is expressed in liver and intestine, and both the neural retina and RPE (Li et al., 2006). In contrast to ApoC-I, it can function as an activator of lipoprotein lipase. Similar to ApoA-I, ApoA-II, and ApoE, in the absence of lipid to stabilize its structure, ApoC-II forms amyloid assemblies. 

The physiological function of heparin is not completely understood. It is found only in trace amounts in normal circulating blood. It exerts an antihpemic effect by releasing lipoprotein lipase from endothehal cells heparinlike proteoglycans produced by endothelial cells have anticoagulant activity. Heparin decreases platelet and inflammatory cell adhesiveness to endothelial cells, reduces the release of platelet-derived growth factor, inhibits tumor cell metastasis, and exerts an antiproliferative effect on several types of smooth muscle. 

Wang C.S., Hartsuck, J., McConathy, W.J. (1992) Structure and functional properties of lipoprotein lipase. Biochim. Biophys. Acta 1123, 1-17. 

Modification of nascent chylomicron particles The particle released by the intestinal mucosal cell is called a "nascent" chylomicron because it is functionally incomplete. When it reaches the plasma, the particle is rapidly modified, receiving apo E (which is recognized by hepatic receptors) and C apolipoproteins, The latter include apo C-ll, which is necessary for the activation of lipoprotein lipase, the enzyme that degrades the triacylglycerol contained in the chylomicron (see below). The source of these apolipoproteins is circulating HDL (see Figure 18.16). 

VLDLs are produced in the liver (Figure 18.17). They are composed predominantly of triacylglycerol, and their function is to carry this lipid from the liver to the peripheral tissues. There, the triacylglycerol is degraded by lipoprotein lipase, as discussed for chylomicrons (see p. 226). [Note "Fatty liver" (hepatic steatosis) occurs in conditions in which there is an imbalance between hepatic triacylglycerol synthesis and the secretion of VLDL. Such conditions include obesity, uncontrolled diabetes mellitus, and chronic ethanol ingestion.]... 

The plasma lipoproteins include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They function to keep lipids (primarily triacylglyc-erol and cholesteryl esters) soluble as they transport them between tissues. Lipoproteins are composed of a neutral lipid core (containing triacylglycerol, cholesteryl esters, or both) surrounded by a shell of amphipathic apolipoproteins, phospholipid, and nonesterified cholesterol. Chylomicrons are assembled in intestinal mucosal cells from dietary lipids (primarily, triacylglycerol) plus additional lipids synthesized in these cells. Each nascent chylomicron particle has one molecule of apolipoprotein B-48 (apo B-48). They are released from the cells into the lymphatic system and travel to the blood, where they receive apo C-ll and apo E from HDLs, thus making the chylomicrons functional. Apo C-ll activates lipoprotein lipase, which degrades the... 

Each apolipoprotein has one or more distinct functions. The apoB proteins probably stabilize the lipoprotein micelles. In addition, apoB-100 is essential to recognition of LDL by its receptors. The 79-residue apoC-II has a specific function of activating the lipoprotein lipase that hydrolyses the triacylglycerols of chylomicrons and VLDL. Lack of either C-II or the lipase results in a very high level of triacylglycerols in the blood.11... 

Chylomicrons transport dietary triacylglycerol and cholesteryl ester from the intestine to other tissues in the body. Very-low-density lipoprotein functions in a manner similar to the transport of endogenously made lipid from the liver to other tissues. These two types of triacylglycerol-rich particles are initially degraded by the action of lipoprotein lipase, an extracellular enzyme that is most active within the capillaries of adipose tissue, cardiac and skeletal muscle, and the lactating mammary gland. Lipoprotein lipase catalyzes the hydrolysis of triacylglycerols (see fig. 18.3). The enzyme is specifically activated by apoprotein C-II, which... 

Figure 3 Function of CETP, LPL (lipoprotein lipase) and HTGL (hepatic triglyceride...

Apolipoprotein C-II can also be isolated from VLDL or HDL (H20, L5, N3). It contains 78 residues (J3) and has been shown by Chou-Fasman analysis to bind phospholipids (M26, M40), with three predicted helical sequences (M26). ApoC-II has attracted a great deal of attention because it activates one of the most important enzymes in plasma lipid metabolism, lipoprotein lipase, responsible for the hydrolysis of triglyceride in chylomicrons and VLDL. Sparrow and Gotto have summarized a number of studies on structure-function relationships (S52). These, taken together, indicate that there are separate functional domains in apoC-II, in that lipoprotein lipase activation is mediated by residues 55-78 and phospholipid binding by... 

In functional lipoprotein lipase deficiency there appears to be a normal removal rate for VLDL from the plasma (B31, F19, N7), and an unimpaired rate for the conversion of VLDL apoB to LDL apoB (N7). It may be that VLDL is hydrolyzed by hepatic triglyceride lipase (unaffected in lipoprotein lipase deficiency) (N7). Hepatic triglyceride lipase does not require apoC-II as a cofactor (E2). 

The milk lipase that is activated by foaming and causes the rancidity of milk is a glycoprotein or a family of glycoproteins. It is inhibited by DFP and is specific for primary ester bonds (14), The physiological function of the lipase is mysterious since new-born animals already possess their own digestive lipases. Milk also contains a lipoprotein lipase which has the properties typical for such an enzyme it is sensitive to heparin and activated by serum proteins. This enzyme is probably serum lipoprotein lipase that has leaked into the milk (14). 

As chylomicrons enter the lymphatic system and the bloodstream, they encounter other lipoprotein particles, such as HDLs. HDLs have a number of functions. One HDL protein, apolipoprotein C-Il (Apo C-II), is transferred from an HDL to a chylomicrim after it leaves the enterocyte Apo Cdl is a cofactor of lipoprotein lipase, an enzyme that resides on the wall of the capillaries in tissues such as muscle and adipose. This enzyme is loosely bound to the lumenal side of the capillary, exposed to the bloodstream. In conjunction with the apo C-II of a chylomicron, it catalyzes the hydrolysis of the TGs of the chylomicron. The free fatty acid products then pass through the wall of the capillary and enter the tissue. 

The function of apoLp-IIl is to facilitate transport of lipid from sites of storage in the fat body to sites of utilization in certain metabolic situations, e.g., flight. The triacylglycerol stores of the fat body are converted to DG, which leaves the fat body and becomes associated with preexisting HDLp in the hemolymph. In the process, HDLp is converted to LDLp and several molecules of apoLp-III become associated with LDLp. LDLp moves to the flight muscle, where the DG is hydrolyzed by a lipoprotein lipase. As the DG is removed, LDLp is converted back to HDLp and apoLp-III dissociates. The HDLp and apoLp-III then cycle back to the fat body to carry more DG (see Section V for details). 

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