Lipoprotein lipases proteins

Gene activated Lipoprotein lipase fatty acid transporter protein adipocyte fatty acid binding protein acyl-CoA synthetase malic enzyme GLUT-4 glucose transporter phosphoenolpyruvate carboxykinase... 

Lipid Transfer Proteins Lipidation Lipopolysaccharide Lipoprotein Lipase... 

FIGURE 3.2.2 Metabolic pathways of carotenoids such as p-carotene. CM = chylomicrons. VLDL = very low-density lipoproteins. LDL = low-density lipoproteins. HDL = high-density lipoproteins. BCO = p-carotene 15,15 -oxygenase. BCO2 = p-carotene 9, 10 -oxygenase. LPL = lipoprotein lipase. RBP = retinol binding protein. SR-BI = scavenger receptor class B, type I. 

TNF (17.5) Monocyte/macrophage, lymphocyte, neutrophil, endothelium, fibroblast, keratinocyte Activation of T and B cells, natural killer cells, neutrophils, and osteoblasts. Stimulation of endothelial cells to release chemotactic proteins, NO and PGI2. Tumoricidal activity. Induces fever, sleep, hepatic acute phase protein synthesis, catabolism, ACTH release. Lead to myocardial depression, hypotension/shock, hypercoagulability, and death. Stimulates production of IL-1, IL-6, IL-8, IFN-y, and H202. Suppression of cytochrome P-450, thyroglobulin, and lipoprotein lipase. Induces complement activation, release of eicosanoids, including PAF. Procoagulant activity. 

Lipoprotein lipases, which act on the lipoproteic bonds of lipoproteins (combinations of proteins with fatty ester molecules), thus breaching the hydrophobic barriers formed by these compounds. 

Hydrolysis of retinyl ester to retinol occurs in the lumen of the small intestine from where it is absorbed with the aid of bile salts, esterified to form retinyl ester and then released into lymph where it is incorporated into chylomicrons. The action of lipoprotein lipase converts chylomicrons to remnants and the retinyl ester remains in the remnants to be taken up by the Uver, where it is stored as the ester until required. On release from the liver, it is transported in blood bound to retinal binding-protein. 

Lipid and lipoprotein acylation stimulating protein, lipoprotein lipase. 

VLDLs, IDLs, and LDLs are closely related to one another. VLDLs formed in the liver (see p. 312) transport triacylglycerols, cholesterol, and phospholipids to other tissues. Like chylomicrons, they are gradually converted into IDL and LDL under the influence of lipoprotein lipase [1]. This process is also stimulated by HDL. Cells that have a demand for cholesterol bind LDL through an interaction between their LDL receptor and ApoB-100, and then take up the complete particle through receptor-mediated endocytosis. This type of transport is mediated by depressions in the membrane ( coated pits"), the interior of which is lined with the protein clathrin. After LDL binding, clathrin promotes invagination of the pits and pinching off of vesicles ( coated vesicles"). The clathrin then dissociates off and is reused. After fusion of the vesicle with ly-sosomes, the LDL particles are broken down (see p. 234), and cholesterol and other lipids are used by the cells. 

Current available information does not permit definitive conclusions on the nature, specificity, and mechanism of action of the protein cofactor (s) of lipoprotein lipase. It is verj difiicult to correlate the observations described above (summarized in Table 10) since the enzyme preparations used were not pure or well characterized, and were derived from various sources. For instance, two species of lipoprotein lipase have been reported to exist in rat adipose tissue (G4), and major differences between enzymes of liver and adipose tissue have been noted (G16). Also, the nature of the apoprotein preparations employed as protein cofactor (s) of lipoprotein lipase has not been clearly specified in all the studies contaminated materials may account for the spurious results observed. At present, it is not known how apoproteins such as apo Glu, apo Ala, and apo Ser could exhibit their activator or inhibitor activity on lipoprotein lipase. If these different apoproteins indeed prove to be cofactors for lipoprotein lipase, the nature of the lipid-protein specificity must be established and thus the role played by carbohydrates, since some of these apoproteins are glycoproteins. 

F3. Fielding, C. J., Lim, C. T., and Scanu, A. M., A protein component of serum high density lipoprotein with cofactor activity against purified lipoprotein lipase. Biochem. Biophys. Res. Commun. 39, 889-894 (1970). 

Mechanism of Action An antihyperlipidemic that enhances synthesis of lipoprotein lipase and reduces triglyceride-rich lipoproteins and VLDLs. Therapeutic Effect Increases VLDL catabolism and reduces total plasma triglyceride levels. Pharmacokinetics Well absorbed from the GI tract. Absorption increased when given with food. Protein binding 99%. Rapidly metabolized in the liver to active metabolite. Excreted primarily in urine lesser amount in feces. Not removed by hemodialysis. Half-life 20 hr. 

Hepatic and peripheral effects of fibrates. These effects are mediated by activation of peroxisome proliferator-activated receptor-a, which modulates the expression of several proteins. LPL, lipoprotein lipase VLDL, very-low-density lipoproteins. 

Progesterone has little effect on protein metabolism. It stimulates lipoprotein lipase activity and seems to favor fat deposition. The effects on carbohydrate metabolism are more marked. Progesterone increases basal insulin levels and the insulin response to glucose. There is... 

Schering Plough demonstrated the kinetic resolution of a secondary amine (24) via enzyme-catalyzed acylation of a pendant piperidine (Scheme 7.13) [32]. The compound 27 is a selective, non-peptide, non-sulfhydryl farnesyl protein transfer inhibitor undergoing clinical trials as a antitumor agent for the treatment of solid tumors. The racemic substrate (24) does not contain a chiral center but exists as a pair of enantiomers due to atropisomerism about the exocylic double bond. The lipase Toyobo LIP-300 (lipoprotein lipase from Ps. aeruginosa) catalyzed the isobu-tylation of the (+) enantiomer (26), with MTBE as solvent and 2,2,2-trifluoroethyl isobutyrate as acyl donor [32]. The acylation of racemic 24 yielded (+) 26 at 97% and (-) 25 at 96.3% after 24h with an E >200. The undesired enantiomer (25)... 

Fig. 5.2.1 The major metabolic pathways of the lipoprotein metabolism are shown. Chylomicrons (Chylo) are secreted from the intestine and are metabolized by lipoprotein lipase (LPL) before the remnants are taken up by the liver. The liver secretes very-low-density lipoproteins (VLDL) to distribute lipids to the periphery. These VLDL are hydrolyzed by LPL and hepatic lipase (HL) to result in intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), respectively, which then is cleared from the blood by the LDL receptor (LDLR). The liver and the intestine secrete apolipoprotein AI, which forms pre-jS-high-density lipoproteins (pre-jl-HDL) in blood. These pre-/ -HDL accept phospholipids and cholesterol from hepatic and peripheral cells through the activity of the ATP binding cassette transporter Al. Subsequent cholesterol esterification by lecithinxholesterol acyltransferase (LCAT) and transfer of phospholipids by phospholipid transfer protein (PLTP) transform the nascent discoidal high-density lipoproteins (HDL disc) into a spherical particle and increase the size to HDL2. For the elimination of cholesterol from HDL, two possible pathways exist (1) direct hepatic uptake of lipids through scavenger receptor B1 (SR-BI) and HL, and (2) cholesteryl ester transfer protein (CfiTP)-mediated transfer of cholesterol-esters from HDL2 to chylomicrons, and VLDL and hepatic uptake of the lipids via the LDLR pathway...

Release of VLDLs VLDLs are secreted directly into the blood by the liver as nascent VLDL particles containing apolipoprotein B-100. They must obtain apo C-ll and apo E from circulating HDL (see Figure 18.17). As with chylomicrons, apo C-ll is required for activation of lipoprotein lipase. [Note Abetalipoproteinemia is a rare hypolipoproteinemia caused by a defect in triacylglycerol transfer protein, leading to an inability to load apo B with lipid. As a consequence, no chylomicrons or VLDLs are formed, and tria-cylglycerols accumulate in the liver and intestine.]... 

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... 

TNF-a is identical to cachetin, a protein that suppresses completely the lipoprotein lipase of adipose tissue and is believed to be responsible for cachexia, a condition of general ill health, malnutrition, weight loss, and wasting of muscle that accompanies cancer and other chronic diseases. Nevertheless, TNF-a may be overproduced in obesity as well. It has been suggested that abnormal production of TNF-a may induce cachexia while abnormal action of the cytokine may cause obesity.233 Some TNF receptors have "death domains" and trigger apoptosis, while other receptors promote proliferation and differentiation via transcription factor NF-kB.242... 

These lipids are then packaged into spherical lipoproteins, particles of lipids and proteins, known as chylomicrons, which are secreted into lymphatic vessels and subsequently enter the blood stream. Once in the circulatory system the triacylglycerol components of the chylomicrons are degraded to fatty acids and glycerol by the enzyme lipoprotein lipase, which is attached to the luminal (inner) side of capillary vessels in heart, muscle, adipose (commonly... 

As the lipoproteins are depleted of triacylglycerol, the particles become smaller. Some of the surface molecules (apoproteins, phospholipids) are transferred to HDL. In the rat, remnants that result from chylomicron catabolism are removed by the liver. The uptake of remnant VLDL also occurs, but much of the triacylglycerol is further degraded by lipoprotein lipase to give the intermediate-density lipoprotein (IDL). This particle is converted into LDL via the action of lipoprotein lipase and enriched in cholesteryl ester via transfer from HDL by the cholesteryl ester transfer protein. The half-life for clearance of chylomicrons from plasma of humans is 4-5 min. Patients with the inherited disease, lipoprotein lipase deficiency, clear chylomicrons from the plasma very slowly. When on a normal diet, the blood from these patients looks like tomato soup. A very-low-fat diet greatly relieves this problem. 

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