title: Carnosine prevents glyceraldehyde 3-phosphate-mediated inhibition of aspartate aminotransferase.
abstract: Post-mitotic tissues, such as the heart, exhibit high concentrations (20 mM) of carnosine (beta-alanyl-l-histidine). Carnosine may have aldehyde scavenging properties. We tested this hypothesis by examining its protective effects against inhibition of enzyme activity by glyceraldehyde 3-phosphate (Glyc3P). Glyc3P is a potentially toxic triose; Glyc3P inhibits the cardiac aspartate aminotransferase (cAAT) by non-enzymatic glycosylation (or glycation) of the protein. cAAT requires pyridoxal 5-phosphate (PyP) for catalysis. We observed that carnosine (20 mM) completely prevents the inhibition of cAAT activity by Glyc3P (5 mM) after brief incubation (30 min at 37 degrees C). After a prolonged incubation (3.25 h) of cAAT with Glyc3P (0.5 mM) at 37 degrees C, the protection by carnosine (20 mM) persisted but PyP availability was affected. In the absence of PyP from the assay medium, cAAT activities (plus Glyc3P) were 95 +/- 18.2 micromol/min per mg protein (mean +/- SD), minus carnosine and 100 +/- 2.4, plus carnosine; control activity was 172 +/- 3.9. When PyP (1.0 microM) was included in the assay medium, cAAT activities (plus Glyc3P) were 93 +/- 14.8, minus carnosine and 151 +/- 16.8, plus carnosine, P < 0. 001; control activity was 180 +/- 17.7. These data, which showed carnosine moderating the effects of both Glyc3P and PyP, suggest that carnosine may be an endogenous aldehyde scavenger.
authors.affiliation: Department of Biochemistry, University of Health Sciences, 1750 Independence Boulevard, Kansas City, MO 64106-1453, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Swearengin
authors.forename: C
authors.initials: C
authors.lastname: Fitzgerald
authors.forename: N W
authors.initials: NW
authors.lastname: Seidler
mesh_terms: D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002336:Carnosine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005986:Glyceraldehyde 3-Phosphate / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology; D011732:Pyridoxal Phosphate / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D005986:Glyceraldehyde 3-Phosphate; D011732:Pyridoxal Phosphate; D002336:Carnosine; D001219:Aspartate Aminotransferases; C004479:pimagedine