Apolipoprotein protein function

Fat, including cholesterol, absorbed from the diet is insoluble in the water-based medium of the blood. To enable transport through the blood system, the various fat components are incorporated into particles called lipoproteins (for reviews on lipoprotein metabolism, see Grundy, 1983 Mahley and Innerarity, 1983). Lipoproteins consist of a lipid core of triglyceride and cholesterol ester with a surface of mainly phospholipid and protein (referred to as apolipoprotein), plus some free cholesterol. The different apolipoproteins present function to regulate lipoprotein metabolism (for review on apolipoproteins, see Mahley et al., 1984). The cholesterol in lipoproteins is mainly transported as cholesterol ester. There are four main lipoprotein fractions found in the blood chylomicrons, very-low density lipoprotein (VLDL), low density Upopro-tein (LDL), and high density lipoprotein (HDL). 

In contrast to MDA and hydroxynonenai, other aldehyde products of lipid peroxidation are hydrophobic and remain closely associated with LDL to accumulate to mil-limolar concentrations. Aldehydes at these elevated levels react with the protein portion of the LDL molecule, apolipoprotein B (apoB). Accumulated aldehydes bind the free amino groups from lysine residues in addition to other functional groups (-OH, -SH) on the apoB polypeptide. Consequently, the protein takes on a net negative charge and complete structural rearrangement results in the formation of ox-LDL. ox-LDL is no longer recognized by the LDL receptor, and has several pro-inflammatory properties (discussed below). 

The method utilizing ID NMR is simple and eonvenient. Henee the NMR method diseussed here ean be applied to the systematie investigation of the membrane irug inter-aetions, elosely related to the vital function in biomembranes. It is expected that the application can be extended to the lipid-peptide interaction and protein uptake. We are now applying the method to apolipoprotein binding with lipid bilayers and emulsions. Preferential protein binding sites in membranes can be specified by NMR on the molecular level. 

In the review dealing with the proteins of plasma lipoproteins, Scanu and Ritter have produced a most lucid and detailed discussion of recent advances in this difficult field. An exciting account is given of the isolation of apolipoproteins, their chemical structure, and what is known of their biological functions lipoproteins relevant to patients with dyslipo-proteinemia are also described. 

Apoliprotein. Any of the protein constituents of lipoproteins, grouped by function in four classes A, B, C, and E (the former apolipoprotein [apo] D is now apo A-111). Apoptosis. Fragmentation of a cell into membrane-bound particles that are eliminated by phagocytosis. Programmed cell death. 

Bianco et al. [34] CNT-r proteins (fibrinogen, protein A, erythropoietin, and apolipoprotein) CNT-TEG-short protein complex quickly entered fibroblasts and other cells, sometimes migrated to their nuclei. Proteins executed their normal biological functions... 

Each class of lipoprotein has a specific function, determined by its point of synthesis, lipid composition, and apolipoprotein content. At least nine different apolipoproteins are found in the lipoproteins of human plasma (Table 21-3), distinguishable by their size, their reactions with specific antibodies, and their characteristic distribution in the lipoprotein classes. These protein components act as signals, targeting lipoproteins to specific tissues or activating enzymes that act on the lipoproteins. 

The molecular basis for the association between apoE4 and Alzheimer s disease is not yet known. Speculation has focused on a possible role for apoE in stabilizing the cytoslceletal structure of neurons. The apoE2 and apoE3 proteins bind to a number of proteins associated with neuronal microtubules, whereas apoE4 does not. This may accelerate the death of neurons. Whatever the mechanism proves to be, these observations promise to expand our understanding of the biological functions of 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). 

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... 

Apolipoprotein A-I is the primary protein component of HDL.23 2513 Most of the 243 residues consist of a nearly continuous amphipathic a helix with kinks at regularly spaced proline residues.26 28 Two disulfide-linked ApoA-I molecules may form a belt that encircles the discoid lipoprotein.2513 ApoA-II is the second major HDL protein, but no dearly specialized function has been identified.29 30 ApoA-I, II, and IV, apoC-I, II, and III, and apoE all have multiple repeats of 22 amino acids with sequences that suggest amphipathic helices. Tire 391-residue ApoA-IV has 13 tandem 22-residue repeats. Proline and glycine are present in intervening hinge regions.23 This may enable these proteins to spread over and penetrate the surfaces of the lipoprotein micelles. Most of these proteins are encoded by a related multigene family.7 303... 

Morais Cabral J. H., Atkins G. L., Sanchez L. M., Lopez-Baodo Y. S., Lopez-Oton C., and Sawyer L. (1995). Arachidonic acid binds to apolipoprotein D Implications for the protein s function. FEBS Lett. 366 53-56. 

Lipoproteins are globular, micelle-like particles consisting of a hydrophobic core of triacylglycerols and cholesterol esters surrounded by an amphipathic coat of protein, phospholipid and cholesterol. The apolipoproteins (apoproteins) on the surface of the lipoproteins help to solubilize the lipids and target the lipoproteins to the correct tissues. There are five different types of lipoprotein, classified according to their functional and physical properties chylomicrons, very low density lipoproteins (VLDLs), intermediate density lipoproteins (IDLs), low density lipoproteins (LDLs), and high density lipoproteins (HDLs). The major function of lipoproteins is to transport triacylglycerols, cholesterol and phospholipids around the body. 

The C apolipoproteins are commonly considered as a group, although they are quite distinct small proteins with different functions. 

Apolipoprotein SAA is one of several proteins which may be associated with plasma lipid, but which do not, as far as we know, have any clear functional role in lipid metabolism. 

Plasma HDL constitute a heterogeneous group of lipoproteins their common property is that they have a hydrated density in the 1.063-1.21 g/ml interval. HDL subfractions are usually described in terms of their hydrated density, but it should not be forgotten that a number of functions may be the property of particular subsets of HDL which can be defined better in terms of their apolipoprotein composition than their hydrated density. A preparation of HDL isolated by flotation in the ultracentrifuge, d between 1.063 and 1.21 g/ml, may contain almost all the major apolipoproteins (except perhaps apoA-IV and apoB-48), together with LCAT and lipid transfer protein. 

Several types of proteins are associated with lipoproteins. These are termed apolipoproteins, or simply apoproteins. Table 19.2 shows the various apolipo-proteins (Apos), their chemical properties and occurrence, and their function, which is discussed later. Note that the A apoproteins are found largely in HDL, the B-100 is found largely in LDL, VLDL, and IDL, and C apoproteins are largely seen in chylomicrons. Nevertheless, there is a large degree of apoprotein overlap among the various lipoprotein classes. 

The LDL receptor is a cell-surface glycoprotein able to bind both apoB, the sole protein of LDL, and apoE, an apolipoprotein that is present in multiple copies on other lipoproteins, including VLDL and IDL, but not LDL. ApoE has a twofold higher affinity than apoB for the receptor, and in general IDL are removed from the circulation more efficiently than LDL. In addition, while its precursors may be metabolized via other pathways, LDL removal from circulation depends heavily on functional LDL receptors. 

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