Fatty acid exogenous

C. D. Stubbs, W. M. Tsang, J. Belin, A. D. Smith, and S. M. Johnson, Incubation of exogenous fatty acids with lymphocytes. Changes in fatty add composition and effects on the rotational relaxation time of l,6-diphenyl-l,3,5-hexatriene, Biochemistry 19, 2756-2762 (1980). 

T.R. de Grado, M.T. Kitapci, S. Wang, J. Ying, Validation of F-fluoro-4-thia-palmitate as a PET probe for myocardial fatty acid oxidation Effects of hypoxia and composition of exogenous fatty acids, J. Nucl. Med. 47 (2006) 173-181. 

T.R. DeGrado, M.T. Kitapci, S. Wang, J. Ying, G.D. Lopaschuk, Validation of F-fluoro-4-thia-palmitate as a PET probe for myocardial fatty acid oxidation Effects of hypoxia and composition of exogenous fatty acids, J. Nucl. Med. 47 (2006) 173-181. T.M. Shoup, D.R. Elmaleh, A.A. Bonab, A.J. Fischman, Evaluation of trans-9- F-fluoro-3,4-methyleneheptadecanoic acid as a PET tracer for myocardial fatty acid imaging, J. Nucl. Med. 46 (2005) 297-304. 

Bly, J.E., T.M. Buttke and L.W. Clem. Differential effects of temperature and exogenous fatty acids on mitogen induced proliferation in channel catfish T and B lymphocytes. Comp. Biochem. Physiol. 95A 417-424, 1990. 

A similar strategy has been developed in the avermectin system, using an S. avermi-tilis strain that lacks a branched-chain a-keto acid dehydrogenase (BCDH) activity. This dehydrogenase activity is required to produce the acyl-CoAs that are required for avermectin biosynthesis, and thus the BCDH mutant is unable to produce avermectin without the addition of exogenous fatty acids to the fermentation media. The addition of isobutyric acid or isovaleric acid allows the production of the natural avermectins, while the addition of non-natural carboxyhc acids results in the production of novel avermectins [92-94]. 

Acetyl CoA is converted to malonyl CoA and into fatty acids as described previously. The enzyme that carries out the first committed step for fatty-acid synthesis, acetyl CoA carboxylase, is finely controlled both allosterically and covalently. This enzyme can occur in a monomeric inactive form or a polymeric active form. One factor that affects this is citrate, which stimulates the polymeric or active form of acetyl CoA carboxylase. Thus, citrate plays an important role in lipogenesis as (1) a source of cytosolic acetyl CoA, (2) an allosteric positive effector of acetyl CoA carboxylase, and (3) a provider of oxaloacetate in the cytosol, which can allow transhydrogenation from NADH to NADPH. An allosteric inhibitor of acetyl CoA carboxylase that causes dissociation to the monomeric form is fatty-acyl CoA. Thus, if exogenous fatty acids are available, there is little reason to synthesize more fatty acids. Fatty-acyl CoA in the cytosol decreases malonyl CoA formation by inhibiting acetyl CoA carboxylase. 

When large amounts of exogenous fatty acid enter the liver, how can they be transferred into the mitochondrion, for beta oxidation, with malonyl CoA inhibition This dichotomy is overcome because fatty-acyl CoAs inhibit acetyl CoA carboxylase and the malonyl CoA present proceeds onto fatty acids. When the malonyl CoA is converted to fatty acid, the level of malonyl CoA drops and is not restored. Thus, the inhibition of acyl carnitine transferase 1 is removed and fatty-acid oxidation can proceed. 

Stubbs, C.D. (1980) Incubation of Exogenous Fatty Acids with Lymphoc3hes. Changes in Fatty Acid Composition and Effect on the Rotational Relaxation Time of 1,6-Diphenyl-... 

It can be seen in Fig. 7 that under our conditions the incorporation of label from added 18 2 in microsomes is an order of magnitude higher than that in mitochondria. Moreover, the formation of the saturated acids, 16 0 and 18 0, is, as would be expected, particularly low in mitochondria (Fig. 8) since a measurement of the percent RCA (relative carboxyl activity) for 14 0 and 16 0 proves them to be formed by a dz novo process, and, in the presence of exogenous fatty acid, is almost completely inhibited (Fig, 7). 

Williams, J.P., Moissan, E., Mitchell, I., and Khan, M.U. (1990) The manipulation of the fatty acid composition of glycerolipids in cyanobacteria using exogenous fatty acid. Plant Cell Physiol. 31, 495-503. 

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