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Query: UMLS:C0694563 (eds)
 1,062 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the presence of phenylalanine and molecular oxygen, activated phenylalanine hydroxylase catalyzes the oxidation of tetrahydrobiopterin. The oxidation of this tetrahydropterin cofactor also proceeds if the substrate, phenylalanine, is replaced by its product, tyrosine, in the initial reaction mixture. These two reactions have been defined as coupled and uncoupled, respectively, because in the former reaction 1 mol of phenylalanine is hydroxylated for every mole of tetrahydrobiopterin oxidized, whereas in the latter reaction there is no net hydroxylation of tyrosine during the oxidation of the tetrahydropterin. During the course of the coupled oxidation of tetrahydrobiopterin, a pterin 4a-carbinolamine intermediate can be detected by ultraviolet spectroscopy (Kaufman, S. (1976) in Iron and Copper Proteins (Yasunobu, K. T., Mower, H. F., and Hayaishi, O., eds) pp. 91-102, Plenum Publishing Corp., New York). Dix and Benkovic (Dix, T. A., and Benkovic, S. J. (1985) Biochemistry 24, 5839-5846) have postulated that the formation of this intermediate only occurs when the oxidation of the tetrahydropteridine is tightly coupled to the concomitant hydroxylation of the aromatic amino acid. However, during the tyrosine-dependent uncoupled oxidation of tetrahydrobiopterin by phenylalanine hydroxylase, we have detected the formation of a spectral intermediate with ultraviolet absorbance that is essentially identical to that of the carbinolamine. Furthermore, this absorbance can be eliminated by the addition of 4a-carbinolamine dehydratase, an enzyme which catalyzes the dehydration of the 4a-carbinolamine. Quantitation of this intermediate suggests that there are two pathways for the tyrosine-dependent uncoupled oxidation of tetrahydrobiopterin by phenylalanine hydroxylase because only about 0.3 mol of the intermediate is formed per mol of the cofactor oxidized.
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PMID:Evidence for the formation of the 4a-carbinolamine during the tyrosine-dependent oxidation of tetrahydrobiopterin by rat liver phenylalanine hydroxylase. 272 90

N alpha-Acetylation is catalyzed by N alpha-acetyltransferases, which transfer acetyl groups from acetyl coenzyme A to the N termini of most eukaryotic proteins co-translationally. NAT1 and ARD1 from the yeast Saccharomyces cerevisiae (Mullen, J. R., Kayne, P. S., Moerschell, R. P., Tsunasawa, S., Gribskov, M., Colavito-Shepanski, M., Grunstein, M., Sherman, F., and Sternglanz, R. (1989) EMBO J. 8, 2067-2075) were previously shown to encode the major N alpha-acetyltransferase, which act on certain proteins having serine, glycine, and alanine but not methionine termini (Sherman, F., Moerschell, R. P., Tsunasawa, S., and Sternglanz, R. (1993) in Methods in Protein Sequence Analysis (Imahori, K., and Sakiyama, F., eds) pp. 173-181, Plenum Publishing Corp., New York). We have identified a second gene, NAT2, that may correspond to the N alpha-acetyltransferase acting on a subset of proteins having methionine termini. Crude extracts of a series of heat-sensitive mutants (Ts-) were screened for acetylation of a 24-amino acid synthetic peptide Met-Asn-Asn- in vitro. One mutant, nat2-1, out of 115 strains examined, lacked acetyltransferase activity, and the mutation co-segregated as a single gene with the heat-sensitive phenotype. The nat2-1 mutants were deficient in the ability to acetylate Met-Asn-Asn- and Met-Glu-Arg-peptides but were able to N alpha-acetylate Ser-Glu-Phe- and Ser-Tyr-Ser- peptides in vitro. The NAT2 wild-type gene was cloned by complementation of the nat2-1 mutant, and the DNA sequence revealed an open reading frame of 288 amino acids. Gene disruption demonstrated that NAT2 is an essential gene, and hybridization analysis indicated that it is located on chromosome VII. Furthermore, there was limited, but significant identities between the yeast N alpha-acetyltransferases Nat1, Ard1, Nat2, and Mak3, although no common motifs could be identified. We propose that NAT2 encodes the major N alpha-acetyl-transferase acting on certain proteins with only methionine termini, and that N alpha-acetylation of some of these proteins is essential for viability.
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PMID:NAT2, an essential gene encoding methionine N alpha-acetyltransferase in the yeast Saccharomyces cerevisiae. 817 41