N-Acetylaspartate synthase is bimodally expressed in microsomes and mitochondria of brain

Zi Hua Lu, Goutam Chakraborty, Robert W. Ledeen, Daniel Yahya, Gusheng Wu

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

N-Acetylaspartate (NAA) is an abundant amino acid derivative of the central nervous system that is localized primarily in neurons and has found widespread use in clinical NMR spectroscopy (MRS) as a non-invasive indicator of neuronal survival and/or viability. Its function, although still obscure, is thought to reflect its unusual metabolic compartmentalization wherein NAA synthase occurs in the neuron and aspartoacylase, the hydrolytic enzyme that removes the acetyl moiety, occurs in myelin and glia. The NAA synthase enzyme, acetyl-CoA/L-aspartate N-acetyltransferase (ANAT), was previously shown to function in mitochondria (MIT), although other subcellular fractions were apparently not examined. In this study we confirmed its presence in MIT but also found significant activity in rat brain microsomes (MIC). The reaction mixture, consisting of [14C]aspartate plus acetyl-CoA in Na-phosphate buffer (pH 7), gave rise to [14C]NAA that was separated and quantified by TLC. Reaction rates were 29.0±0.46 and 6.27±0. 27 nmol/h/mg for MIC and MIT, respectively. Km values and pH optima were similar, and both fractions showed modest enhancement of ANAT activity with the detergents Triton CF-54 and CHAPS. Our tentative conclusion is that ANAT is bimodally targeted to MIT and a component of MIC - likely endoplasmic reticulum. ANAT activity increased in both MIC and MIT between 29 and 60 days of age but differed thereafter in that only MIT ANAT showed a decrease after 1 year.

Original languageEnglish (US)
Pages (from-to)71-78
Number of pages8
JournalMolecular Brain Research
Volume122
Issue number1
DOIs
StatePublished - Mar 17 2004

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Molecular Biology

Keywords

  • ANAT
  • Acetyl-CoA/L-aspartate N-acetyltransferase (NAA-synthase)
  • Brain microsomes and mitochondria
  • DTT
  • Dithiothreitol
  • ER
  • Endoplasmic reticulum
  • Enzyme property
  • INT
  • Multiple sclerosis
  • Myelin lipid synthesis
  • N-Acetylaspartate
  • N-Acetylaspartate synthase

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