Disease relevance of alpha-Aminoadipic acid

• alpha-Hydroxyglutarate as an intermediate in the catabolism of alpha-aminoadipate by Pseudomonas putida [1].
• The thermophilic bacterium Thermus thermophilus synthesizes lysine through the alpha-aminoadipate pathway, which uses alpha-aminoadipate as a biosynthetic intermediate of lysine [2].
• Delta-1-Piperideine-6-carboxylate (P6C) dehydrogenase activity, which catalyses the conversion of P6C into alpha-aminoadipic acid, has been studied in the cephamycin C producer Streptomyces clavuligerus by both spectrophotometric and radiometric assays [3].
• 4. The results are discussed in terms of the mechanism of action of alpha aminoadipate in causing toxicity of glial cells [4].
• Moreover, the most notable effect was the appearance in urine and plasma of 2-aminoadipate, which has previously been shown to lead to neurological effects in rats [5].

High impact information on alpha-Aminoadipic acid

• These two genes share a common ancestor with the ribosomal protein S6:glutamate ligase and a putative alpha-aminoadipate ligase, defining the first group of ATP-grasp enzymes with a shared amino acid substrate specificity [6].
• Moreover, the pipecolate catabolite alpha-aminoadipate decreased 30-fold in RNA interference plants [7].
• Time-dependent acylation of alpha-AAR and of fragments containing the adenylation domain with tritiated alpha-aminoadipate occurred in vitro in the absence of NADPH [8].
• The expression of the structural genes for lysine (LYS) biosynthesis is controlled by a pathway-specific regulation mediated by the transcriptional activator Lys14 in the presence of alpha-aminoadipate semialdehyde, an intermediate of the pathway acting as a co-inducer [9].
• The catabolic function of the alpha-aminoadipic acid pathway in plants is associated with unidirectional activity of lysine-oxoglutarate reductase, but not saccharopine dehydrogenase [10].

Chemical compound and disease context of alpha-Aminoadipic acid

• Lysine catabolism in Streptomyces spp. is primarily through cadaverine: beta-lactam producers also make alpha-aminoadipate [11].
• Aspartate kinase-independent lysine synthesis in an extremely thermophilic bacterium, Thermus thermophilus: lysine is synthesized via alpha-aminoadipic acid not via diaminopimelic acid [12].

Biological context of alpha-Aminoadipic acid

• Inhibition of cell proliferation and concomitant astrogliosis by 5-fluorodeoxyuridine and alpha-aminoadipic acid abolishes the trophic effect [13].
• Altered cell morphologies, including increased size, multiple buds, pseudohyphae, and germ tubes, evidenced by cells grown in alpha-aminoadipate medium suggest that higher-than-supplementary levels of alpha-aminoadipate result in an impairment of cell division [14].
• Sequence analysis of a gene cluster involved in the lysine biosynthesis of this microorganism suggested that the conversion from alpha-aminoadipate to lysine proceeds in a way similar to that of arginine biosynthesis [15].
• Unlike most of the other MX cassettes, the LYS5MX cassettes are also negatively selectable (alpha-aminoadipate-resistant), which will allow the use of the LYS5MX cassettes in plasmid shuffling and will also greatly facilitate marker recycling [16].
• This phenotype was complemented to the wild-type by supplementation of the medium with both L-lysine and alpha-aminoadipic acid, or transformation using cosmid cosGTM [17].

Anatomical context of alpha-Aminoadipic acid

• Selective ablation of astrocytes by intracerebral injections of alpha-aminoadipate [18].
• Effects of alpha-aminoadipate isomers on the morphology of the isolated chick embryo retina [19].
• The integrity of astrocytes was evaluated at several time points following a single injection of alpha-aminoadipate into amygdala of adult rats using immunohistochemistry [18].
• Intracellular recordings of the light response of retinal Müller glial cells revealed differential effects of optical isomers of alpha-aminoadipic acid, a putative gliotoxin [20].
• To inhibit glial function, fluorocitrate (FC), a reversible metabolic inhibitor, or alpha-aminoadipate (alpha-AA), an irreversible toxin, was injected into the dentate gyrus region, and the regulation of [K+]o was monitored for 8 h or 2 days later, respectively [21].

Associations of alpha-Aminoadipic acid with other chemical compounds

• The relative specific radioactivities of the alpha-aminoadipyl and penicillamine moieties of the penicillin were the same (within experimental error) as those of the alpha-aminoadipic acid and valine residues respectively of the tripeptide [22].
• 3. The behaviour of the labelled alpha-aminoadipic acid from the penicillin to the L-amino acid oxidase of Crotalus adamanteus venom showed that it was mainly L-alpha-aminoadipic acid [22].
• After performic acid oxidation and ion-exchange chromatography, analysis of the peptide fractions by two-dimensional thin-layer electrophoresis and chromatography revealed the presence of three related peptides, as sulfonic acid derivatives, each containing alpha-aminoadipic acid [23].
• Our studies of a mentally retarded male with extremely elevated levels of alpha-aminoadipic acid and alpha-ketoadipic acid in his urine have led to the description of a new metabolic defect, alpha-ketoadipic aciduria [24].
• A comparison of the effects of isomers of alpha-aminoadipic acid and 2-amino-4-phosphonobutyric acid on the light response of the müller glial cell and the electroretinogram [20].

Gene context of alpha-Aminoadipic acid

• The alpha-aminoadipate reductase (AAR) of this pathway catalyzes the conversion of alpha-aminoadipic acid to alpha-aminoadipic-delta-semialdehyde by a complex mechanism involving two gene products, Lys2p and Lys5p [25].
• Lysine biosynthesis in yeast requires the posttranslational conversion of the alpha-aminoadipate semialdehyde reductase Lys2 by the 4'-phosphopantetheinyl transferase (PPTase) Lys5 from the inactive apo-form into the catalytically active holo-form [26].
• Maximum likelihood, neighbor joining, and maximum parsimony phylogenetic comparisons show that the alpha-aminoadipate pathway enzyme is an outgroup to all aconitase family proteins for which sequence is currently available [27].
• In mammals, the conversion of alpha-aminoadipate to alpha-ketoadipate by alpha-aminoadipate aminotransferase (AADAT) is an intermediate step in lysine degradation [28].
• In mammals, L-lysine is first catabolized to alpha-aminoadipate semialdehyde by the bifunctional enzyme alpha-aminoadipate semialdehyde synthase (AASS), followed by a conversion to alpha-aminoadipate by alpha-aminoadipate semialdehyde dehydrogenase [29].

Analytical, diagnostic and therapeutic context of alpha-Aminoadipic acid

• These results indicate that alpha-adminoadpic acid can be used to substantially reduce the number of astroglia in cerebellar cultures and that dissociated cell cultures will provide a useful model with which to study the mechanisms of alpha-aminoadipic acid induced glial toxicity [30].
• Treatment with alpha-aminoadipic acid resulted in rapid nuclear and cytoplasmic swelling and, after longer periods of exposure, karyopyknosis of astrocytes, identified by indirect immunofluorescence labelling with anti-human glial fibrillary acidic protein antiserum [30].
• Moreover, we found a new, as yet unidentified amino acid in the brain eluting with the same retention time as alpha-aminoadipic acid from an HPLC cation-exchange column [31].
• Development of the neonatal rabbit retina in organ culture. 1. Comparison with histogenesis in vivo, and the effect of a gliotoxin (alpha-aminoadipic acid) [32].
• Twenty-four hr after intraventricular injection of L-[14C]lysine to the monkey, substantial labeling of pipecolate and alpha-aminoadipate was observed in the brain and spinal cord, with the kidney, liver and the plasma having much reduced levels [33].

References