Proteins apolipoprotein

In 1993/1994 a series of publications caused a stir in the AD research community, since for the first time they linked a specific neuropathological process in late-onset AD to a genetic marker. Researchers looking at the composition of plaques found that the protein apolipoprotein E (ApoE) was associated with p-amyloid in the cerebrospinal fluid (CSF) of AD patients (Strittmatter et al., 1993). The gene for ApoE is on the same human chromosome (number 19) which was a risk factor in some AD pedigrees. The gene for ApoE comes in three versions (alleles) Apo s2, Apo s3 and, most importantly, Apo s4 these result in three slightly different variants of the protein. Humans carry two versions of the allele and so can have none, one or two of any of the versions of the Apo... 

Serum amyloids Coagulation factors Tumor necrosis factor Erythrocyte proteins Apolipoproteins... 

In adipose tissue, TAG is stored in the cytosol of the cells in a nearly anhydrous form. It serves as "depot fat," ready for mobilization when the body requires it for fuel. Little TAG is stored in the liver. Instead, most is exported, packaged with cholesteryl esters, cholesterol, phospholipid, and protein (apolipoprotein B-100, see p. 229) to form lipoprotein particles called very low density lipoproteins (VLDL). Nascent VLDL are secreted into the blood where they mature and function to deliver the endogenously-derived lipids to the peripheral tissues. [Note Recall that chylomicrons deliver primarily dietary (exogenously-derived) lipids.] Plasma lipoproteins are discussed in Chapter 18, p. 225. 

The plasma lipoproteins are spherical macromolecular complexes of lipids and specific proteins (apolipoproteins or apoproteins). The lipoprotein particles include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They differ in lipid and protein composition, size, and density (Figure 18.13). Lipoproteins function both to keep their component lipids soluble as they transport them in the plasma, and also to provide an efficient mechanism for transporting their lipid contents to (and from) the tissues. In humans, the transport system is less perfect than in other animals and, as a result, humans experience a yradual deposition of lipid—especially cholesterol—in tissues. This is a potentially life-threat-en ng occurrence when the lipid deposition contributes to plaque formation, causing the narrowing of blood vessels (atherosclerosis). 

The mixture of lipids moves to the endoplasmic reticulum, where fatty acyl CoA synthetase converts free fatty acids into their activated CoA derivatives. Fatty acyl CoAs are then used to produce triacylglycerols, cholesteryl esters, and phospholipids. These, together with the fat-soluble vitamins (A, D, E, and K) and a single protein (apolipoprotein B-48), form a chylomicron, which is secreted into the lymphatic system and carried to the blood. 

Keywords Alzheimer s disease Parkinson s disease Presenilin Amyloid precursor protein Apolipoprotein E Synuclein Parkin LRRK2 PINKl neurodegeneration... 

Keywords Amyloid precursor protein Apolipoprotein E p-amyloid peptide Beta-amyloid precursor protein converting enzyme Insulin degrading enzyme Neurofibrillary tangle Oxidative damage Presenilin-1... 

Lipoproteins are macromolecules comprising proteins (= apolipoproteins, apoproteins) and lipids. They transport water-insoluble lipids in the blood, with the exception of the albumin-bound free fatty acids. Only short-chain fatty acids are dissolved in plasma. The lipoproteins are formed in the liver and in the mucosa of the small intestine. (14)... 

Children suffering from malnutrition sometimes accumulate deposits of fat in the liver. This condition, called a fatty liver, may result from failure to synthesize specific proteins (apolipoproteins) used for the packaging and export of fat from the liver. These proteins arc components of the VLDLs, as discussed in Chapter 6. 

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 lipids of the diet include TGs, phospholipids, cholesteryl esters, cholesterol, and the fat-soluble vitamins. These nutrients require special types of biochemical machinery to facilitate their assimilation and distribution within the body. The biochemical apparatus used includes bile salts, apolipoproteins, serum albumin, and vitamin-binding proteins. Apolipoproteins are the primary subject of this section. The term apolipoprotein is used when referring only to the protein, whereas the term lipoprotein refers to the complex of apolipoprotein and lipid. 

The triacylglycerols are incorporated into a heterogeneous population of spherical lipoprotein particles known as chylomicrons (diameter, 75-600 nm) that contain about 89% triacylglycerol, 8% phospholipid, 2% cholesterol, and 1 % protein. Phospholipids of the chylomicron arise by de novo synthesis (Chapter 19) or from reacylation of absorbed lysolecithin. Cholesterol is supplied by de novo synthesis (Chapter 19) or is absorbed. The protein apolipoprotein B-48 (apo B-48) forms a characteristic protein complement of chylomicrons and is synthesized in the enterocyte. Synthesis of apo B-48 is an obligatory step in chylomicron formation. Absence of apo B-48 synthesis, as in the rare hereditary disease abetalipoproteinemia,... 

A lipoprotein particle has a shell composed of proteins (apolipoproteins) and a cholesterol-containing phospholipid monolayer (Figure 18-12). The shell is amphipathic because its outer surface is hydrophilic, making these particles water soluble, and its inner surface is hydrophobic. Adjacent to the hydrophobic inner surface of the shell is a core of neutral lipids containing mostly cholesteryl esters, triglycerides, or both. Small amounts of other hydrophobic compounds (e.g., vitamin E, carotene) also are carried in the lipoprotein core. 

Lipoproteins are soluble complexes of proteins (apolipoproteins) and lipids that transport lipids in the circulation of all vertebrates and even insects. Lipoproteins are synthesized in the liver and the intestines, arise from metabolic changes of precursor lipoproteins, or are assembled at the cell membranes from cellular lipids and exogenous lipoproteins or apolipoproteins. In the circulation, lipoproteins are highly dynamic. They undergo enzymatic reactions of their lipid components, facilitated and spontaneous lipid transfers, transfers of soluble apolipoproteins, and conformational changes of the apolipoproteins in response to the compositional changes. Finally, lipoproteins are taken up and catabolized in the liver, kidney, and peripheral tissues via receptor-mediated endocytosis and other mechanisms. This chapter deals with the composition and structure of human lipoproteins. 

Three major alleles of the APOE gene (APOE2, APOE3, and APOE4), which codes for the plasma protein apolipoprotein E (apoE), have been studied for their associations with plasma lipoprotein concentrations. Polymorphisms in the APOE gene have been shown to influence plasma lipoprotein concentrations in carriers of certain alleles. Specifically, the E4 allele has been associated with increased LDL-C, whereas the E2 allele has been linked with lower LDL-C." Both E2 and E4 have been linked with increased plasma triglycerides."... 

Lipoproteins are molecular aggregates that transport water-insoluble lipids in the blood plasma they contain a core of neutral lipids, coated with a monolayer of phospholipids in which special proteins (apolipoproteins) and cholesterol are embedded. The interaction of apolipoprotein A-I with PC-coated mercury proceeds in steps when increasing progressively its bulk concentration, ca-i [48]. For ca-i < 4 pg cm the differential capacity minimum C is not affected, but the concomitant decrease in the orientation peaks of PC points to an interaction of apoA-I... 

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