Aspartate metabolism, regulation

Fig. 2 Metabolic pathways in C. glutamicum for biosynthesis of the aromatic amino acids tryptophan, tyrosine, and phenylalanine (a) and amino acids belonging to the aspartate family including lysine, methionine, threonine, and isoleucine (b). Metabolic regulation by feedback inhibition is indicated by dotted lines...

ATCase and many (but not all) enzymes subject to metabolic regulation have a second interesting property their reaction velocity is not a hyperbolic function of substrate (aspartate) concentration, as... 

PEPCs from enterobacteria such as Salmonella typhimurium and Escherichia coli are activated by acetyl CoA and inhibited by aspartate. Some properties of the enzyme from Rhodopseudomonas sp. No.7 were similar to those of the enterobacteria. However, the strain No.7 enzyme was different from enzymes of the enterobacteria in important points of metabolic regulation. It have been reported that the enzyme activities of the enterobacteria were increased by FBP and GTP. In contrast with this, the activity of the No.7 enzyme was not affected by FBP and reversibly inhibited by GTP and ATP (ADP). This differences may signify roles of the enzyme of strain No.7 related to the ethanol-assimilation and the enzymes of the enterobacteria to the glucose-assimilation in their own way. 

Methionine biosynthesis is controlled by the metabolic regulation of enzymes in the pathway. Species of Corynebacterium and Brevibacterium have much simpler regulatory mechanisms than E. coli for methionine biosynthesis and are the preferred microbes for overproduction. Aspartokinase is a major enzyme that catalyzes the phosphorylation of aspartic acid and redirects the flux to aspartate family of amino acids. 

This list is not intended to be comprehensive but to indicate the wide array of neuronal proteins regulated by phosphorylation. Some of the proteins are specific to neurons but most are present in many cell types in addition to neurons and are included because their multiple functions in the nervous system include the regulation of neuron-specific phenomena. Not included are the many phosphoproteins present in diverse tissues, including brain, that play a role in generalized cellular processes, such as intermediary metabolism, and that do not appear to play a role in neuron-specific phenomena. NMDA, N-methyl-D-aspartate CREB, cAMP response element-binding proteins STAT, signal-transducing activators of transcription ... 

Proteins are often organized into large complexes, sometimes for the purpose of regulating metabolism. An example is aspartate carbamoyltransferase... 

Enzymes that are susceptible to direct regulation occupy key positions in metabolic pathways. In a multistep pathway the first enzyme in the pathway is usually regulated, and the others are not (fig. 11,8a). In the case of CTP synthesis (see chapter 9), we saw that the enzyme aspartate car-... 

Rakhmanova, T.I., Popova, T.N. (2006). Regulation of 2-oxoglutarate metabolism in rat liver by NADP-isocitrate dehydrogenase and aspartate aminotransferase. Biochemistry (Mosc.) 71(2) 211-17. 

Several aaRS-like proteins are involved in metabobc pathways (1). For example, E. coli asparagine synthase, an aspartyl-tRNA synthetase (AspRS)-like enzyme, catalyzes the synthesis of asparagine from aspartate and ATP. A paralog of LysRS-II, called PoxA/GenX, is important for pyruvate oxidase activity in E. coli and Salmonella typhimurium and for virulence in S. typhimurium. The E. coli biotin synthetase/repressor protein (BirA), which has a domain that resembles structurally the seryl-tRNA synthetase (SerRS) catalytic domain, activates biotin to modify posttranslationaUy various metabolic proteins involved in carboxylation and decarboxylation. BirA can also bind DNA and regulate its own transcription using biotin as a corepressor. A histidyl-tRNA synthetase (HisRS)-hke protein from Lactococcus lactis, HisZ is involved in the allosteric activation of the phosphoribosyl-transferase reaction. 

Like motor traffic, metabolic pathways flow more efficiently when regulated by signals. CTP, the final product of a multistep pathway, controls flux through the pathway by inhibiting the committed step catalyzed by aspartate transcarbamoylase (ATCase).[(Left) Richard Berenholtz/The Stock Market.]... 

Brain extracellular concentrations of amino acids and divalent metals (e.g., manganese) are primarily regulated by astrocytes. Adequate glutamate homeostasis is essential for the normal functioning of the central nervous system (CNS), for example, glutamate is important for nitrogen metabolism and, along with aspartate, is the primary mediator of the excitatory... 

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