Endoplasmic reticulum lipid synthesis

Membrane-lipid synthesis continues in the endoplasmic reticulum. Phospholipid synthesis requires the combination of a diacyl glycerol with an alcohol. As in most anabolic reactions, one of the components must be activated. In this case, either the diacylglerol or the alcohol may be activated, depending on the source of the reactants. 

Like other cells, a neuron has a nucleus with genetic DNA, although nerve cells cannot divide (replicate) after maturity, and a prominent nucleolus for ribosome synthesis. There are also mitochondria for energy supply as well as a smooth and a rough endoplasmic reticulum for lipid and protein synthesis, and a Golgi apparatus. These are all in a fluid cytosol (cytoplasm), containing enzymes for cell metabolism and NT synthesis and which is surrounded by a phospholipid plasma membrane, impermeable to ions and water-soluble substances. In order to cross the membrane, substances either have to be very lipid soluble or transported by special carrier proteins. It is also the site for NT receptors and the various ion channels important in the control of neuronal excitability. 

The lipid compositions of plasma membranes, endoplasmic reticulum and Golgi membranes are distinct 26 Cholesterol transport and regulation in the central nervous system is distinct from that of peripheral tissues 26 In adult brain most cholesterol synthesis occurs in astrocytes 26 The astrocytic cholesterol supply to neurons is important for neuronal development and remodeling 27 The structure and roles of membrane microdomains (rafts) in cell membranes are under intensive study but many aspects are still unresolved 28... 

The 3 10 cells in the liver—particularly the hepatocytes, which make up 90% of the cell mass—are the central location for the body s intermediary metabolism. They are in close contact with the blood, which enters the liver from the portal vein and the hepatic arteries, flows through capillary vessels known as sinusoids, and is collected again in the central veins of the hepatic lobes. Hepatocytes are particularly rich in endoplasmic reticulum, as they carry out intensive protein and lipid synthesis. The cytoplasm contains granules of insoluble glycogen. Between the hepatocytes, there are bile capillaries through which bile components are excreted. 

Glycerol for milk lipid synthesis is obtained in part from hydrolysed blood lipids (free glycerol and monoglycerides), partly from glucose and a little from free blood glycerol. Synthesis of triglycerides within the cell is catalysed by enzymes located on the endoplasmic reticulum, as shown in Figure 3.13. 

The endoplasmic reticulum is composed of a convoluted network of channels and so has a large surface area. Apart from cytochromes P-450, the endoplasmic reticulum has many enzymes and functions, besides the metabolism of foreign compounds. These include the synthesis of proteins and triglycerides and other aspects of lipid metabolism and fatty acid metabolism. Specific enzymes present on the endoplasmic reticulum include cholesterol esterase, azo reductase, glucuronosyl transferase, NADPH cytochromes P-450 reductase and NADH cytochrome b5 reductase and cytochrome b5. A FAD-containing monooxygenase is also found in the endoplasmic reticulum, and this is discussed later in this chapter. 

Smooth endoplasmic reticulum (SER) is site of lipid synthesis and drug metabolism... 

Although palmitate, a 16-carbon, fully saturated LCFA (16 0), is to primary end-product of fatty acid synthase activity, it can be further I elongated by the addition of two-carbon units in the endoplasmic] reticulum (ER) and the mitochondria. These organelles use separate enzymic processes. The brain has additional elongation capabilities, allowing it to produce the very-long-chain fatty acids (up to 24 car bons) that are required for synthesis of brain lipids. 

Because phospholipid synthesis occurs on the cytosolic side of the endoplasmic reticulum and phospholipids are found on both leaflets of the bilayer, how do these lipids reach the inner leaflet of the bilayer Possibly proteins called flipases catalyze the movement of phospholipids from one side of the bilayer to the other. More research is... 

The synthesis of the apoproteins takes place on ribosomes that are bound to the endoplasmic reticulum. As we mentioned previously, the biosynthesis of the other lipids in lipoproteins (cholesterol, triacylglycerols, and phospholipids) also occurs on the endoplasmic reticulum. 

The rough endoplasmic reticulum contains ribosomes on the surfaces, a cell structure that will be discussed in the next section. The system formed by endoplasmic reticulum and ribosomes is associated with protein synthesis. The endoplasmic reticulum also participates in lipid biosynthesis. In different types of eukaryotic cells, the endoplasmic reticulum has different forms and functions. In muscle cells, in which Ca2+ stimulates contraction, the endoplasmic reticulum participates in the relaxation process, reabsorbing Ca2+ ions. 

The synthesis of the ceramide lipid moiety of GSLs is initiated in the endoplasmic reticulum (ER) (6) via the condensation of serine and palmitoylCoA. This enzyme has been cloned (7). The product is 3-keto-sphinganine that then is reduced to sphinga-nine and acylated by ceramide synthase with a long-chain fatty acid to form dihydroceramide, which is converted to ceramide by ceramide desaturase, which inserts the 4,5-trans double bond. 

In eucaryotic cells, glycolysis, gluconeogenesis and fatty acid synthesis takes place in the cytosol, while the Krebs cycle is isolated within mitochondria glycogen is made in glycogen granules, lipid is synthesized in the endoplasmic reticulum and lysosomes carry on a variety of hydrolytic activities. As in procaryotic cells, ribosomes in the cytosol are the site of protein synthesis. 

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