title: Catabolism of intracellular N-terminal acetylated proteins: involvement of acylpeptide hydrolase and acylase.
abstract: Protein acylation processes involve the covalent attachment of acyl moieties to the alpha- and epsilon-amino groups of polypeptide chains. The N-terminal blocking of proteins occurs in a wide range of eukariotic cells, where more than 50% of the cytosolic proteins can be N-alpha-acetylated. The acetylation which occurs during or after the biosynthesis of the polypeptide chains serves to protect the intracellular proteins from proteolysis. Food processing can also generate N-alpha-acetylated proteins and peptides. The mechanism underlying the intracellular catabolism of N-acetylated proteins has not yet been elucidated, however. It is generally assumed that two enzymes are involved in the hydrolysis of the N-terminal part of the proteins. The NH(2)-blocked peptides generated during proteolysis may be cleaved by an N-acylpeptide hydrolase (APH). This releases the N-terminal amino acid, which is in turn deacetylated by an aminoacylase, the most common of which is aminoacylase 1 (ACY 1). The corresponding free amino acid is therefore available for protein synthesis. Both APH and ACY 1 are cytoplasmic enzymes, which have been isolated from various mammalian tissues. APH belongs to a novel class of serine-type peptidases called the prolyl oligopeptidase (PROP) family. ACY 1 belongs to the M20 metalloenzyme family. In this review, the processes involved in alpha- and epsilon-acetylation and the catabolism of endogenous proteins and proteins involved in food processing are discussed. We then focus on the characteristics of the APH and ACY 1 enzymes involved in the final release of the free amino acids, which are essential to protein synthesis.
authors.affiliation: Institut Méditerranéen de Recherche en Nutrition, Inra-UMR 1111 service 342, Université Paul Cézanne, Aix-Marseille, Faculté des Sciences et Techniques, Avenue Escadrille Normandie Niemen, F-13397 Marseille cedex 20, France. josette.perrier@univ.u-3mrs.fr
authors.forename: Josette
authors.initials: J
authors.lastname: Perrier
authors.forename: Anne
authors.initials: A
authors.lastname: Durand
authors.forename: Thierry
authors.initials: T
authors.lastname: Giardina
authors.forename: Antoine
authors.initials: A
authors.lastname: Puigserver
mesh_terms: D000107:Acetylation; D000581:Amidohydrolases / Q000737:chemistry / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D006868:Hydrolysis; D008956:Models, Chemical; D008958:Models, Molecular; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D000085822:Prolyl Oligopeptidases; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D051381:Rats; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D000596:Amino Acids; D010455:Peptides; D011506:Proteins; D010447:Peptide Hydrolases; C038220:acylaminoacyl-peptidase; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases; D000581:Amidohydrolases; C019672:aminoacylase I