1. A new synaptosomal biosynthetic pathway of glutamate and GABA from ornithine and its negative feedback inhibition by GABA
Y Yoneda, E Roberts, G W Dietz Jr J Neurochem. 1982 Jun;38(6):1686-94. doi: 10.1111/j.1471-4159.1982.tb06650.x.
In sonicates of mouse brain synaptosomes, we demonstrated that gamma-aminobutyric acid (GABA) can be formed when L-ornithine (Orn) through L-glutamic acid (Glu), but not through putrescine (Put). Incubation of these sonicates with [3H]ORN yielded not only [3H]Glu and [3H]L-proline (Pro) but also produced [3H]GABA from the [3H]Glu. Formation of each of these three major amino acids from [3H]Orn was strongly inhibited by the addition of GABA (1-5 mM). The likely enzymatic site of this negative feedback inhibition by GABA appeared to be ornithine delta-aminotransferase (OAT). A radiometric procedure was employed to study the effects of the three amino acids cited above and of others found in the free form in brain on the activity of a 30-fold-purified OAT from rat brain. Enzyme activity was measured in the presence of low concentrations of Orn, such as might occur in vivo. OAT was inhibited by GABA to a considerably greater extent than by Glu, L-glutamine, or Put; no inhibition was found with Pro, glycine, aspartarte, taurine, or beta-alanine. The inhibition of GABA was competitive with Orn. These results clearly show that one of the molecular mechanisms underlying the negative feedback inhibition of synaptosomal GABA biosynthesis from Orn is a competitive inhibition by GABA of the brain OAT activity that is responsible for the formation of L-glutamic-gamma-semialdehyde in equilibrium with L-delta 1-pyrroline-5-carboxylic acid from Orn. Thus, the results suggest that GABA may play an important role in restricting the metabolic flow from Orn to Glu and thence to GABA. It is confirmed that L-canaline (delta-aminooxy-L-alpha-aminobutyric acid) is a potent and specific inhibitor of brain OAT whereas much weaker inhibition was observed with two other carbonyl-trapping agents, aminooxyacetic acid and hydrazine.
2. Gratuitous repression of avtA in Escherichia coli and Salmonella typhimurium
W A Whalen, C M Berg J Bacteriol. 1984 May;158(2):571-4. doi: 10.1128/jb.158.2.571-574.1984.
avtA , which encodes transaminase C (alanine-valine transaminase), is repressed by excess-L-alanine or L-leucine, and also by limitation for any of a number of amino acids in Escherichia coli and Salmonella typhimurium. Amino acid limitation causes repression by promoting the accumulation of L-alanine or L-leucine or both. avtA is also repressed by L-alpha-aminobutyric acid and other nonprotein amino acids which are structurally similar to L-alanine. We hypothesize that L-alanine and L-alpha-aminobutyric acid, whose syntheses are catalyzed by transaminase C, are the true corepressors of avtA . Repression by structural analogs of the true corepressors is termed gratuitous repression.
3. Identification of Serum Biomarkers and Pathways of Systemic Lupus Erythematosus with Skin Involvement Through GC/MS-Based Metabolomics Analysis
Yongyi Xie, Baoyi Liu, Zhouwei Wu Clin Cosmet Investig Dermatol. 2022 Jan 18;15:77-86. doi: 10.2147/CCID.S345372. eCollection 2022.
Purpose: Skin involvement is the second most common symptom of systemic lupus erythematosus (SLE), and the prevention of skin lesion development might benefit to lessen the system inflammation burden in SLE. However, the mechanisms of skin lesion in SLE remain unclear. Patients and methods: Metabolome based on gas chromatography-mass spectrometry (GC-MS) was used for comparison of serum metabolism among 11 SLE patients with skin lesion (SL), 10 SLE patients without skin lesion (SNL), and 16 healthy controls (HC). The analysis of metabolism profiles was through LUG database, Human Metabolome Database (HMDB) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: A total of 14 most meaningful metabolites were found in SL patients compared to SNL patients, and 19 metabolic pathways were enriched. Meanwhile, L-alpha-aminobutyric acid, dehydroascorbic acid, glycine, and L-tyrosine achieved an area under receiver-operating characteristic (ROC) curve of 0.8636, 0.8091, 0.7727, and 0.7636, respectively, indicating their diagnostic potential for SL patients. In addition, the combined model of L-alpha-aminobutyric acid and dehydroascorbic acid provided better diagnostic accuracy. Conclusion: The metabolomic features of SLE patients with skin lesion could be detected by GC/MS assay. Our study tried to provide new insights into the mechanism of SLE skin injury. Further validation of these findings through larger sample size studies may contribute to the use of metabolic profile analysis.