Fatty acid activating enzyme and

Cinnamyl anthranilate has the characteristic effects of a peroxisome proliferator on mouse liver, increasing the activity of peroxisomal fatty acid-metabolizing enzymes and microsomal CYP4A and increasing hepatocellular proliferation. These effects are mediated by the intact ester, and were not seen after administration of the hydrolysis products, cinnamyl alcohol and anthranilic acid. The corresponding effects on rat liver were very much weaker. No relevant data from humans were available. 

The acyl CoA synthetase that activates long-chain fatty acids, 12 to 20 carbons in length, is present in three locations in the cell the endoplasmic reticulum, outer mitochondrial membranes, and peroxisomal membranes (Table 23.1). This enzyme has no activity toward C22 or longer fatty acids, and little activity below C12. In contrast, the synthetase for activation of very-long-chain fatty acids is present in peroxisomes, and the medium-chain-length fatty acid activating enzyme is present only in the mitochondrial matrix of liver and kidney cells. 

As can be seen from Table 1, the specific activity of long chain acyl CoA synthetase is significantly depressed in the Novikoff hepatoma and host liver when compared with normal liver. These results agree with those of Weinhouse et al. (1973) that made it clear that the activity of the fatty acid activating enzyme is very low in poorly differentiated hepatomas. There is no doubt that the growing tumor exerts a profound effect on the enzyme system of the host liver. On the other hand, no significant differences were observed in the activity of long chain acyl CoA thioesterase from the tissues under study. 

Fatty acids are oxidized only in the form of fatty a< l-CoA derivatives, and mitochondria from mammalian tissues contain the full equipment of enzymes necessary for the synthesis and the degradation of fatty acyl-CoA. The enzymes involved in the oxidative process are located in the mitochondrial matrix, and the inner mitochondrial membrane sequesters the oxidative process from the rest of these organelles. On the contrary, the fatty acids activating enzymes (thiokinase) seem to be present in different compartments of the mitochondrion and widely distributed among the subcellular fractions. The significance of this may lie in the fact that the conditions required for fatty acyl-CoA oxidation differ from those required for other CoA—SH dependent pathways. 

Acetate and fatty acid activation enzymes - —acetylation of ATP with formation of acetyl AMP and PPi, replacement of AMP by CoA. 

CoA and fatty acid activating enzymes in rat liver mitochondria. Eur. Biochem. 14 465 (1970). ... 

Short-chain acyl-CoA synthetase activates short-chain fatty acids, acetic, butyric and propionic acid. The enzyme is present in both the cytosol and in the mitochondrial matrix of most tissues the activity is especially high in the liver and the colon. 

The final step in signal transduction is the action of cAMP on the regulatory subunit of the enzyme, protein kinase A. This ubiquitous enzyme then phosphorylates and activates enzymes with functions specific to different cells and organs. In fat cells, protein kinase A activates lipase, which mobilizes fatty acids in muscle and liver cells, it regulates glycogenolysis and glycogen synthesis. 

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