N-acyltransferase

It has recently been demonstrated (191) that the nature and location of lipid A primary fatty acids is determined by the specificity of the enzymes UDP-GlcpNAc-G-acyltransferase and UDP-3-6>-[(i )-hydroxyacyl]-GlcpN-N-acyltransferase for acyl - acyl carrier protein (acyl ACP). The analysis of the acyl ACP specificity of these O- and A-acyltransferases should, therefore, constitute a biochemical approach for elucidation of the location of primary fatty acids in lipid A (191). 

The S-CoA derivative then acylates the amino group of the particular amino acid in an analogous way to the acetylation of amine groups described above, yielding a peptide conjugate. This is catalyzed by an amino acid N-acyltransferase, which is located in the mitochondria. Two such enzymes have been purified, each using a different group of CoA derivatives. 

The pineal gland appears also to play a role in maintaining the mammalian circadian cycle.1081-1083 The concentration of the pineal hormone melatonin (Fig. 27-11) as well as its precursor N-acetylserotonin and the enzyme serotonin N-acetyltransferase (Eq. 30-4) all fluctuate far more than do the concentrations of other metabolites during the 24-h cycle. These metabolites increase over 10-fold concentration at night and decrease by day. During the daytime the serotonin N-acyltransferase, which forms the precursor, is rapidly... 

Figure 10.6. The biosynthesis of endocannabinoids. Biosynthetic pathways for the biosynthesis of the major endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG). Note that the enzymes N-acyltransferase in anandamide biosynthesis. The biosynthesis of 2-AG can proceed via two different routes and is also dependent on an increase in Ca. Figures reprinted from Piomelli (2003) with permission from Nature Publishing Group.

Conversion of the carboxylic acid to its CoA ester derivative is the rate-limiting step. The enzyme that catalyzes the final reaction, acyl-CoA amino acid N-acyltransferase, is localized in the mitochondria of the kidney and liver. The amino acid substrate selectivity, which varies from species to species, resides in the specific N-acyltransferase that... 

Gregersen N> Kolvraa S, Mortensen PB. Acyl-CoA glycine N-acyltransferase in vitro studies on the glycine conjugation of straight- and branched-chained acyl-CoA esters in human liver. Biochem MedMetab Biol 1986 35 210-8. 

In Vitro Studies. An assay for measuring taurine N-acyltransferase activity with C-phonylacetyl CoA as substrate has boon described (79). Enzyme activity was located In the matrix of the mitochondrion and was usually higher In kidney than liver for the nine fish species studied. Studies with Isolated renal tubules from the winter flounder and the southern flounder (84 and James and Pritchard, unpublished) have shown that added phenylacetlc acid and benzoic acid were extensively metabolized to their taurine conjugates during a 60 minute Incubation. 

NAA, or lAA ( ). In vitro studies with enzymes from mammals suggest that xenobiotic carboxylic acids are activated by a reaction that requires ATP and CoA. The xenobiotic acyl-CoA derivative is then released from the enzyme surface. The initial activation reactions are catalyzed by different acyl-CoA synthetase enzymes with different substrate specificities. Benzoic and phenylacetlc acid derivatives are activated by what appears to be a butyrl-CoA synthetase present in the mitochondrial matrix. The final reaction is catalyzed by an acyl-CoA amlno acid N-acyltransferase. Two closely related forms have been purified from bovine liver mitochondria. 

The most important mammalian conjugation molecules for pollutants and their metabolites are uronic acids, glutathione, amino acids, taurine, and sulphate. The conjugation is catalyzed by liver enzymes like UDP-glucuronyl-transferases, sulfotransferases, glutathione S-transferases and amino acid N-acyltransferases. 

The metabolism of xenobiotic carboxylic acids to amino acid conjugates involves a two-step enzymatic pathway in which the xenobiotic is first activated in an ATP-dependent reaction to the corresponding coenzyme A thioester. This in turn serves as the substrate for an N-acyltransferase that catalyzes the formation of the peptide bond... 

A2AKK5 Acyl-coenzyme A amino acid N-acyltransferase 1 46,070 8 1.0000 2 2... 

Mandala, SM, Thornton, RA, Frommer, BR, Curotto, JE, Rozdilsky, W, Kurtz, MB, Giacobbe, RA, Bills, GF, Cabello, MA, Martin, 1 et al. (1995) The discovery of austrahfungin, a novel inhibitor of sphinganine N-acyltransferase from Sporormiella austrahs. Producing organism, fermentation, isolation, and biological activity. J Antibiot (Tokyo), 48, 349-356. 

Gupta SD, Gan K, Schmid MB, Wu HC (1993) Characterization of a temperature-sensitive mutant of Salmonella typhimurium defective in apolipoprotein N-acyltransferase. J Biol Chem 268 16551-16556... 

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