Fatty acid cellular site

Very-Low-Density Lipoproteins (VLDL) are less dense than chylomicrons. They contain more protein, although lipids (fatty acids, cholesterol and phospholipid, in that order) still make up 90 to 95 percent of their weight. Low-density lipoproteins (LDLs) are about 85 percent lipid by weight and contain more cholesterol than any other kind of lipid. VLDL and LDL contain large amounts of Apolipoprotein B. The VLDL and LDL are sometimes referred to as bad cholesterol because elevated serum concentrations of these lipoproteins correspond with a high incidence of artery disease (stroke and heart disease). The LDLs carry cholesterol and fatty acids to sites of cellular membrane synthesis. 

The processes of electron transport and oxidative phosphorylation are membrane-associated. Bacteria are the simplest life form, and bacterial cells typically consist of a single cellular compartment surrounded by a plasma membrane and a more rigid cell wall. In such a system, the conversion of energy from NADH and [FADHg] to the energy of ATP via electron transport and oxidative phosphorylation is carried out at (and across) the plasma membrane. In eukaryotic cells, electron transport and oxidative phosphorylation are localized in mitochondria, which are also the sites of TCA cycle activity and (as we shall see in Chapter 24) fatty acid oxidation. Mammalian cells contain from 800 to 2500 mitochondria other types of cells may have as few as one or two or as many as half a million mitochondria. Human erythrocytes, whose purpose is simply to transport oxygen to tissues, contain no mitochondria at all. The typical mitochondrion is about 0.5 0.3 microns in diameter and from 0.5 micron to several microns long its overall shape is sensitive to metabolic conditions in the cell. 

P2 is a component of myelin from the peripheral nervous system. It is localized on the cytoplasmic side of Schwann cells where it behaves as peripheral membrane protein, although a small amount is found in the cytoplasm (Trapp et al., 1984). Like the other iLBPs, the exact biochemical role of P2 is unknown. Its cellular localization and its ability to bind different fatty acids and retinoids (Uyemura et al., 1984) suggest that it may function in fatty acid trafficking. It would therefore play a major role in the movement of fatty acids between the site of uptake and that of esterification during the massive phospholipid synthesis phase of myelinating Schwann cells. 

Although the mitochondria are the primary site of oxidation for dietary and storage fats, the peroxisomal oxidation pathway is responsible for the oxidation of very long-chain fatty acids, jS-methyl branched fatty acids, and bile acid precursors. The peroxisomal pathway also plays a role in the oxidation of dicarboxylic acids. In addition, it plays a role in isoprenoid biosynthesis and amino acid metabolism. Peroxisomes are also involved in bile acid biosynthesis, a part of plasmalogen synthesis and glyoxylate transamination. Furthermore, the literature indicates that peroxisomes participate in cholesterol biosynthesis, hydrogen peroxide-based cellular respiration, purine, fatty acid, long-chain... 

Although fatty acid synthesis occurs within the cytoplasm of most animal cells, liver is the major site for this process. (Recall, for example, that liver produces VLDL. See p. 349.) Fatty acids are synthesized when the diet is low in fat and/or high in carbohydrate or protein. Most fatty acids are synthesized from dietary glucose. As discussed, glucose is converted to pyruvate in the cytoplasm. After entering the mitochondrion, pyruvate is converted to acetyl-CoA, which condenses with oxaloacetate, a citric acid cycle intermediate, to form citrate. When mitochondrial citrate levels are sufficiently high (i.e., cellular energy requirements are low), citrate enters the cytoplasm, where it is cleaved to form acetyl-CoA and oxaloacetate. The net reaction for the synthesis of palmitic acid from acetyl-CoA is as follows ... 

Henneberry, A. L., M. M. Wright, and C. R. McMaster. 2002. The major sites of cellular phospholipid synthesis and molecular determinants of fatty acid and lipid head group specificity. Mol. Biol. Cell 13 3148-3161. 

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