Publications

• Biosynthesis of Carnosine and Related Dipeptides in Vertebrates.

  Kwiatkowski S., Kiersztan A., Drozak J.

  Carnosine (β-alanyl-L-histidine) and its methylated derivatives: anserine (β-alanyl-Nπ-methyl-L-histidine) and balenine (β-alanyl-Nτ-methyl-L-histidine) are abundant constituents of excitable tissues of vertebrates. While carnosine and anserine are present at high concentrations and in variable pr ... >> More

  Carnosine (β-alanyl-L-histidine) and its methylated derivatives: anserine (β-alanyl-Nπ-methyl-L-histidine) and balenine (β-alanyl-Nτ-methyl-L-histidine) are abundant constituents of excitable tissues of vertebrates. While carnosine and anserine are present at high concentrations and in variable proportions in skeletal muscle and brain of most vertebrates, balenine appears to be rather more abundant in marine mammals and certain reptilian species. Since the discovery of these compounds at the beginning of 20th century, numerous studies have been devoted to identification of the biochemical and physiological properties of carnosine and related dipeptides. These led to the discovery of the pHbuffering, metal-chelation and antioxidant, capabilities of carnosine and anserine, although no definitive ideas concerning their physiological role has yet been formulated. Only recently the molecular identities of the enzymes catalyzing synthesis of carnosine (carnosine synthase, EC 6.3.2.11) and anserine (carnosine N-methyltransferase, EC 2.1.1.22) have been elucidated, which has given a new insight into their metabolism in vertebrates. These findings have opened new research areas and provide authentic opportunities for understanding the biological function of these "enigmatic" dipeptides. This review aims to summarize recent advances in our knowledge concerning enzymes responsible for the biosynthesis of carnosine and related dipeptides and to evaluate their importance in vertebrate physiology. << Less

  Curr Protein Pept Sci 19:771-789(2018) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.

• Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1).

  Drozak J., Veiga-da-Cunha M., Vertommen D., Stroobant V., Van Schaftingen E.

  Carnosine (beta-alanyl-L-histidine) and homocarnosine (gamma-aminobutyryl-L-histidine) are abundant dipeptides in skeletal muscle and brain of most vertebrates and some invertebrates. The formation of both compounds is catalyzed by carnosine synthase, which is thought to convert ATP to AMP and ino ... >> More

  Carnosine (beta-alanyl-L-histidine) and homocarnosine (gamma-aminobutyryl-L-histidine) are abundant dipeptides in skeletal muscle and brain of most vertebrates and some invertebrates. The formation of both compounds is catalyzed by carnosine synthase, which is thought to convert ATP to AMP and inorganic pyrophosphate, and whose molecular identity is unknown. In the present work, we have purified carnosine synthase from chicken pectoral muscle about 1500-fold until only two major polypeptides of 100 and 90 kDa were present in the preparation. Mass spectrometry analysis of these polypeptides did not yield any meaningful candidate. Carnosine formation catalyzed by the purified enzyme was accompanied by a stoichiometric formation, not of AMP, but of ADP, suggesting that carnosine synthase belongs to the "ATP-grasp family" of ligases. A data base mining approach identified ATPGD1 as a likely candidate. As this protein was absent from chicken protein data bases, we reconstituted its sequence from a PCR-amplified cDNA and found it to fit with the 100-kDa polypeptide of the chicken carnosine synthase preparation. Mouse and human ATPGD1 were expressed in HEK293T cells, purified to homogeneity, and shown to catalyze the formation of carnosine, as confirmed by mass spectrometry, and of homocarnosine. Specificity studies carried out on all three enzymes were in agreement with published data. In particular, they acted with 15-25-fold higher catalytic efficiencies on beta-alanine than on gamma-aminobutyrate. The identification of the gene encoding carnosine synthase will help for a better understanding of the biological functions of carnosine and related dipeptides, which still remain largely unknown. << Less

  J. Biol. Chem. 285:9346-9356(2010) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.