The occurrence of N‐acetylaspartate amidohydrolase (Aminoacylase II) in the developing rat¹

Abstract

Of The amino acids and derivatives, N‐acetyl‐L‐aspartic acid is present in a uniquely high level (5–6 μmol/g) in the brain of mammals after myelination has occurred. Much lower levels (0·06–0·17 μmol/g) are found prior to this stage of brain development (Tallan, 1957). In non‐nervous tissues, on the other hand, only trace amounts of this acetyl amino acid are present (Tallan, Moore and Stein, 1956). N‐acetyl aspartic acid serves as an excellent source of acetyl groups for lipogenesis in the developing rat brain (D'Adamo and Yatsu, 1966; Dadamo, Gidez and Yatsu, 1968). Non‐nervous tissues such as kidney and mammary gland also rapidly metabolize the acetyl amino acid, the former tissue converting the acetyl group primarily to CO2 and the latter to fatty acids (Benuck and D'Adamo, 1968). An enzyme with a high specificity for N‐acetyl‐L‐aspartic acid initially termed aminoacylase II, was originally isolated from hog kidney by Birnbaumet al. (1952). Since the physiological role of the substrate is not known, it was of interest to study the occurrence of this enzyme, N‐acetyl‐L‐aspartate amidohydrolase (EC 3.5.1.15), in developing tissues of the rat.

Canavan disease, a rare early-onset human spongiform leukodystrophy: Insights into its genesis and possible clinical interventions

“…Another used global ischemia to induce depolarization and found that NAA increased 5e10 times in the perfusate [25]. The calculated half-life of released NAA is very short being of the order of seconds to minutes [26], and as a consequence the neuron to ECF NAA gradient in brain would be expected to be high. Evidence of this has been obtained based on rat brain microdialysis studies, where the normal steady-state concentration of NAA in GM ECF was found to be very low (about 20 mM) at any given moment [27].…”

Expression of aspartoacylase (ASPA) and Canavan disease

“…Seven amino acids (Arg63, Asn70, Arg71, Tyr164, Arg168, Glu178 and Tyr288) form the catalytic site of the enzyme, in which Arg168 and Tyr288 stabilize NAA binding to the active site (Bitto et al, 2007;Le Coq et al, 2008). ASPA is present in various tissues, but predominantly in the kidney and white matter of the brain, specifically in oligodendrocytes (Baslow et al, 1999;Birnbaum et al, 1952;D'Adamo et al, 1973;Madhavarao et al, 2004). Genetic deficiency of ASPA follows an autosomal-recessive trait of inheritance and is the cause of Canavan disease (CD) (Kaul et al, 1993).…”

N-Acetylaspartate (NAA) and N-Acetylaspartylglutamate (NAAG) Promote Growth and Inhibit Differentiation of Glioma Stem-like Cells

“…Although NAA is of neuronal origin, its primary site of catabolism is in oligodendrocytes where it is hydrolyzed by the enzyme aspartoacylase (ASPA) to generate free acetate and aspartate (9). NAA-derived acetate needs to be converted to acetyl-coenzyme A (acetyl-CoA) via the cytosolic/nuclear enzyme acetyl-CoA synthetase 1 (AceCS1) for lipid biosynthesis and histone/protein acetylation (10) or mitochondrial acetyl-CoA synthetase 2 for use in the Krebs cycle (11).…”