Long-chain fatty acids phosphorylation

A modified form of P-oxidation is found in peroxisomes and leads to the formation of acetyl-CoA and H2O2 (from the flavoprotein-linked dehydrogenase step), which is broken down by catalase. Thus, this dehydrogenation in peroxisomes is not linked directly to phosphorylation and the generation of ATP. The system facilitates the oxidation of very long chain fatty acids (eg, Cjq, C22). These enzymes are induced by... 

Figure 12.12 Sphingomyelins. Sphingomyelins are esters of a ceramide and phospho-ryl choline. However, similar compounds are ceramide-1-phosphoryl ethanolamines and phosphono forms of sphingolipids. Ceramides W-acyl-sphingosines) are amides of a long chain di- or trihydroxy base containing 12 to 22 carbon atoms, of which sphingosine (4-sphingenine) is the commonest, and a long chain fatty acid whose acyl chain is shown by R1. This may contain up to 26 carbon atoms.

Having shown that dibutyryl PC is monomeric under the enzyme assay conditions, we found that the phospholipase A2, which acts poorly on PE in mixed micelles, is activated by dibutyryl PC which is itself an even poorer substrate. 31p-NMR spectroscopy was employed to show that only PE is hydrolyzed in mixtures of various compositions of these two phospholipids. The fully activated enzyme hydrolyzes PE at a similar rate to its optimal substrate, PC containing long-chain fatty acid groups. Because dibutyryl PC is not incorporated into the micelles, these results are consistent with a mechanism of direct activation of the enzyme by phosphoryl-choline-containing lipids (either monomeric or micellar) rather than a change in the properties of the interface being responsible for the activation of phospholipase A2. Therefore, two functional sites on the enzyme have to be assumed an activator site and a catalytic site (6). 

Kim KH, Lopez-Casillas F, Bai DH, Luo X, Pape ME. Role of reversible phosphorylation of acetyl-CoA carboxylase in long-chain fatty acid synthesis. FASEB J 3 2250-2256, 1989. 

Figure 7-1. Pathways of fuel metabolism and oxidative phosphorylation. Pyruvate may be reduced to lactate in the cytoplasm or may be transported into the mitochondria for anabolic reactions, such as gluconeogenesis, or for oxidation to acetyl-CoA by the pyruvate dehydrogenase complex (PDC). Long-chain fatty acids are transported into mitochondria, where they undergo [ -oxidation to ketone bodies (liver) or to acetyl-CoA (liver and other tissues). Reducing equivalents (NADH, FADII2) are generated by reactions catalyzed by the PDC and the tricarboxylic acid (TCA) cycle and donate electrons (e ) that enter the respiratory chain at NADH ubiquinone oxidoreductase (Complex 0 or at succinate ubiquinone oxidoreductase (Complex ID- Cytochrome c oxidase (Complex IV) catalyzes the reduction of molecular oxygen to water, and ATP synthase (Complex V) generates ATP fromADP Reprinted with permission from Stacpoole et al. (1997).

From this discussion, it follows that the activity of the PDC tends to be directly associated with high rates of ATP turnover or high concentrations of pyruvate, that is, conditions during which the oxidative removal of glucose, lactate, and pyruvate is accelerated. In contrast, PDC activity tends to be inversely associated with diversion of these substrates toward gluconeoge-nesis. A reciprocal relationship exists in some tissues between the oxidation of carbohydrate and long-chain fatty acids that is mediated, in part, by the ratio of phosphorylated/unphos-phorylated PDC. This phenomenon, termed the glucose-fatty acid cycle, is best demonstrable... 

LAP also appears to play several critical functions. LAP plays an important role in fatty acid absorption. LAP is able to dephosphor-ylate the phosphorylated fatty acid translocase FAT/CD36, which is thought to play a role in facilitating the transport of long-chain fatty acids into cells. In addition, Uke TNAP, LAP is able to dephos-phorylate LPS. The locahzation of the active site of LAP into the gut lumen allows LAP to protect gut barrier function and determine the composition of the gut microbiota. These functions of LAP, Uke those of TNAP, may have very important therapeutic appUcations. 

Long Chain Fatty Acids Esterifled with Phosphoryl Groups Lipid Bilayer of Bacterial Membranes... 

Pozzan T, Rizzuto R, Volpe P, Meldolesi J (1994) Molecular and cellular physiology of intracellular calcium stores. Physiol Rev 74 595-636 Raeymakers L, Wuytack F (1996) Calcium pumps. In Barany M (ed) Biochemistry of smooth muscle contraction. Academic Press, San Diego, pp 241-253 Rembold CM (1990) Modulation of the [Ca " ] sensitivity of myosin phosphorylation in intact swine arterial smooth muscle. J Physiol 429 77-94 Rembold CM, Weaver BA (1990) [Ca ], not diacylglycerol, is the primary regulator of sustained swine arterial smooth muscle contraction. Hypertension 15 692-698 Shimada T, Somlyo AP (1992) Modulation of voltage-dependent Ca channel current by arachidonic acid and other long-chain fatty acids in rabbit intestinal smooth muscle. J Gen Physiol 100 27-44... 

Triacylglycerols are hydrolysed by lipolytic enzymes (lipases) in a step-wise fashion ultimately to yield glycerol and long chain fatty acids. In S. cerevisiae, lipase action is located in the plasma membrane [70]. Phospholipid hydrolysis is catalysed by phospholipases yielding glycerol and fatty acids, as well as products such as choline etc. Glycerol may be phosphorylated, oxidized and enter the EMP pathway as dihydroxyacetone phosphate. The long chain fatty acids are presumed to be converted to acetyl CoA by the p-oxidation pathway (Fig. 17.17). This pathway may be located either within the mitochondria or microbodies. 

Schonfeld, P., Schild, L., Kunz, W. (1989). Long-chain fatty acids act as protonophoric uncouplers of oxidative phosphorylation in rat liver mitochondria. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 977(3), 266-272. 

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