Bile-acyl group, transference

Based on the results reported above, it was suggested that the microsomes are bearcra of the bile acid activating enzyme system and the lysosomes or perhaps the peroxisomes are bearers of the enzyme or enzymes that catalyze the transference of the bile-acyl group from bile-acyl-iS-CoA to taurine and glycine, e.g., according to Bremer (1956c) the bile acyl transferase I and the bile acyl transferase II. 

ACAT transfers amino-acyl groups from one molecule to another. ACAT is an important enzyme in bile acid synthesis, and catalyses the intracellular esterification of cholesterol and formation of cholesteryl esters. ACAT-mediated esterification of cholesterol limits its solubility in the cell membrane and thus promotes accumulation of cholesterol ester in the fat droplets within the cytoplasm this process is important in preventing the toxic accumulation of free cholesterol that would otherwise damage ceU-membrane structure and function. Most of the cholesterol absorbed during intestinal transport undergoes ACAT-mediated esterification before incorporation into chylomicrons. In the liver, ACAT-mediated esterification of cholesterol is involved in the production and release of apo-B-containing lipoproteins. 

Transacylation reversible transfer of acyl groups (R-CO-) from a donor to an acceptor, e.g. transfer of the acyl residue CH3-CO- from acetyl-CoA to an acceptor Y CH3-CO - S-CoA -t Y -> CH3-CO-Y + CoA. T. is catalysed by transacylases, which are important in the synthesis and degradation of fatty acids, synthesis of conjugated bile acids via cholic acid-CoA compounds, and other reactions such as acetylation of amino acids and amines. 

Much of the cholesterol synthesis in vertebrates takes place in the liver. A small fraction of the cholesterol made there is incorporated into the membranes of he-patocytes, but most of it is exported in one of three forms biliary cholesterol, bile acids, or cholesteryl esters. Bile acids and their salts are relatively hydrophilic cholesterol derivatives that are synthesized in the liver and aid in lipid digestion (see Fig. 17-1). Cholesteryl esters are formed in the liver through the action of acyl-CoA-cholesterol acyl transferase (ACAT). This enzyme catalyzes the transfer of a fatty acid from coenzyme A to the hydroxyl group of cholesterol (Fig. 21-38), converting the cholesterol to a more hydrophobic form. Cholesteryl esters are transported in secreted lipoprotein particles to other tissues that use cholesterol, or they are stored in the liver. 

Bremer (1962a,b) and Fritz and Yuc (1963, 1964) liave presented experimental support that activated fatty acid, acyl-CoA, and even acetyl-CoA, are functionally compartmented in the cell and that the transport between the compartments is probably facilitated by the transfer of the acyl or acetyl group to carnitine, forming an energy-rich compound, acyl-camitine and acetyl-carnitine, respectively. The probable compart-mentation of these acyl-CoA esters seems to make it appear less likely that bile-acjd-CoA is a transport form within the cell. It is, however, not known whether there i.s a transport which corresponds to carnitine for bilc-acyl-CoA. 

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