title: Aspartate aminotransferase in synaptic and nonsynaptic mitochondria: differential effect of compounds that influence transient hetero-enzyme complex (metabolon) formation.
abstract: The enzyme aspartate aminotransferase (AAT) has a number of key roles in astrocytes and neurons in brain. An understanding of the regulation of AAT is important since AAT is involved in many aspects of glutamate metabolism including the synthesis of neurotransmitter glutamate. Mitochondrial AAT binds to a protein and lipids on the inner mitochondrial membrane and also forms a number of transient hetero-enzyme complexes with other enzymes. These complexes serve to facilitate metabolism by essentially channeling substrates and cofactors to other enzymes within the complex. The association and dissociation of transiently formed hetero-enzyme complexes may modulate enzyme activity in "real time" since these complexes are dynamically influenced by changes in the concentration of a number of key metabolites. The influence of several effectors that modulate AAT activity, either directly, or by altering the binding of AAT to mitochondrial lipids, or the association/dissociation into transient hetero-enzyme complexes was determined. The addition of palmitate, malate, citrate, glutamate, bovine serum albumin and Mg(2+) modulated AAT activity differently in synaptic and nonsynaptic mitochondria from brain. These findings suggest that AAT activity and also glutamate metabolism, may be regulated in part, by metabolites that influence binding of the enzyme to lipids or proteins in the inner mitochondrial membrane and/or the association/dissociation of transient hetero-enzyme complexes. This may have a role in the compartmentation of glutamate metabolism in brain.
authors.affiliation: Department of Pediatrics, University of Maryland School of Medicine, Baltimore, 21201, USA. mmckenna@umaryland.edu
authors.forename: Mary C
authors.initials: MC
authors.lastname: McKenna
authors.forename: Irene B
authors.initials: IB
authors.lastname: Hopkins
authors.forename: Steven L
authors.initials: SL
authors.lastname: Lindauer
authors.forename: Penelope
authors.initials: P
authors.lastname: Bamford
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism*; D002540:Cerebral Cortex / Q000201:enzymology / Q000648:ultrastructure; D019343:Citric Acid / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008293:Malates / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology*; D051336:Mitochondrial Membranes / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects* / Q000201:enzymology* / Q000648:ultrastructure
chemical_list: D008293:Malates; D009097:Multienzyme Complexes; D012710:Serum Albumin, Bovine; D019343:Citric Acid; D019308:Palmitic Acid; D018698:Glutamic Acid; D008345:Manganese; C030298:malic acid; D001219:Aspartate Aminotransferases