Regulation of mammalian aspartate-4-decarboxylase: its possible role in oxaloacetate and energy metabolism

A newly discovered enzyme in mammalian tissues, aspartate-4-decarboxylase (EC 4.1.1.12), catalyzes the exothermic conversion of aspartate to alanine and CO2. The occurrence of this enzyme poses at least two important questions. First, what is the purpose of such an enzyme in cell physiology? There are alternate ways to convert aspartate to alanine which are rapid and which conserve energy. Second, since the synthesis of aspartate is an energy-requiring process, how can the cell limit undue energy drain by this, seemingly pointless, beta-decarboxylation of aspartate? It is demonstrated that rat liver aspartate-4-decarboxylase is inhibited by acetyl-coenzyme A and stimulated by glutamate. These regulatory properties were predicted a priori. It was suggested that, in coordination with pyruvate carboxylase, aspartate-4-decarboxylase is important in regulating the metabolic fate of oxaloacetate and thus plays a role in determining the efficiency of carbohydrate metabolism. Furthermore, reciprocal regulation of rat liver pyruvate carboxylase and aspartate-4-decarboxylase would assure a limit on the extent of futile cycling that may occur between these enzymes.     

Evidence for Compromised Insulin Signaling and Neuronal Vulnerability in Experimental Model of Sporadic Alzheimer’s Disease

Evidence from animal studies categorizes sporadic Alzheimer’s disease (sAD) as a metabolic syndrome with accompanying cognitive deficits. Given that glial cells act as “silent partners” to neurons by providing trophic support and defense, the present study investigated the role of glia in sAD pathology. A streptozotocin (STZ)-induced glial-neuronal co-culture model of sAD was used to study the metabolic status of the two cell types. Real time RT-PCR and Western blotting results indicated that amyloid precursor protein (APP) and β-secretase (BACE1) were highly expressed in co-cultured neurons than in monocultures. Increased amyloidogenesis was accompanied by decreased expression of mediators in insulin signaling pathway that included insulin receptor (IR), insulin receptor substrate 2 (IRS2), insulin-like growth factor 2 (IGF2), insulin-like growth factor 1 receptor (IGF1R), total-glycogen synthase kinase 3β (t-GSK3β), and phosphorylated-GSK3β^ser9 (p-GSK3β^ser9), suggesting that neuronal cells are more prone to metabolic variability when cultured in the presence of glial cells. Findings from the sAD model induced by intracerebroventricular (ICV) injection of STZ revealed that increased amyloid beta (Aβ) load in the hippocampus was potentially responsible for the hyperphosphorylation of tau at ser³⁹⁶. Furthermore, impaired cognitive functions and decreased dendritic spine density and axonal thinning in CA1 region of hippocampus were associated with decreased IR and p-GSK3β^ser9/t-GSK3β expression. Taken together, the present study provides evidence that glia mediated response and insulin signaling defects drive pathological changes in sAD and represent potential targets for delaying sAD progression.     

Synthesis,Molecular Docking,and In Vitro Antibacterial Activities of Some Novel Aminobenzylnaphthol Derivatives via One-Pot Three-Component Reaction

Russian Journal of Bioorganic Chemistry - This work provides the first example of incorporating the thiazole moiety into the aminobenzylnaphthol i.e. Betti base. A series of novel synthesized Betti...     

Genetic relationships among five nemipterid fish species from the Indian coast using allozyme analysis

Based on Nei's genetic distance Nemipterus peronii and Nemipterus japonicus showed a greater affinity to Parascolopsis aspinosa than to the other Nemipterus species studied. Significant differences between the Indian west and east coast samples of N. japonicus were detected. Polymorphic (P<0.95) and diagnostic loci suitable for stock delineation and species identification were observed.