Pathways anaplerotic

Pyruvate carboxylation in astrocytes is the major anaplerotic pathway in brain 544... 

Glutamate Glucose Investigation of the roles of anaplerotic pathways in glutamate overproduction [119]... 

The metabolic flux distributions around the intermediate pyruvate for different strains and environmental conditions are summarised in Fig. 12. This part of the metabolism has been shown to be an important node for the interconversion between glycolytic C3 metabolites and C4 metabolites of the tricarboxylic acid (TCA) cycle. The different anaplerotic reactions are of special importance for the production of recombinant proteins as they provide precursors, such as oxaloace-tate, for amino acid biosynthesis. Due to that, the flux distribution is noticeably affected by both the cultivation conditions and the carbon source used which indicates flexible adaptation to the environmental situation. The flux from pyruvate to oxaloacetate through the reaction catalysed by pyruvate carboxylase was found to be the main anaplerotic pathway in B. megaterium. 

Intermediates in the citric acid cycle are involved in many other metabolic pathways of the cell, including amino acid metabolism (see below), gluconeogenesis, and fatty acid metabolism (see here and here). Thus, the amounts of citric acid cycle intermediates will vary according to the metabolic needs of the cell. Replacement of citric acid cycle intermediates occurs via anaplerotic pathways. These pathways function in most cells to keep intramitochondrial concentration of citric acid cycle intermediates fairly constant with time. Figure 14.18 depicts several anaplerotic pathways and these are summarized below ... 

F. 20.19. Major anaplerotic pathways of the TCA cycle. 1 and 3 (blue arrows) are the two major anabohc pathways. (1) Pyruvate carboxylase (2) Glutamate is reversibly converted to a-ketoglutarate by transaminases (TA) and glutamate dehydrogenase (GDH) in many tissues. (3) The carbon skeletons of valine and isoleucine, a 3-carbon unit from odd chain fatty acid oxidation, and a number of other comprounds enter the TCA cycle at the level of succinyl CoA. Other amino acids are also degraded to fumarate (4) and oxaloacetate (5), principally in the liver. 

H. (2007) Study on roles of anaplerotic pathways in glutamate overproduction of Corynehacterium glutamicum by metabolic flux analysis. Microb. Cell Fact, 6 (1), 19. 

Sato, H., Orishimo, K., Shirai, T., Hirasawa, T., Nagahisa, K., Shimizu, H., and Wachi, M. (2008) Distinct roles of two anaplerotic pathways in glutamate production induced by biotin limitation in Corynebacterium glutamicum. 

Glycorata pathway an anaplerotic pathway which enables the utilization of glyoxylate in plants and microorganisms TWo molecules of glyoxylate are converted to tartronate semialdehyde by tartronate... 

Engineering Anaplerotic Pathways or Precursor Supply Chain... 

Metabolic flux through the anaplerotic pathways (the intermediate pathways) will be limiting for amino acid production. Overexpression or deletion of the anaplerotic enzymes may help direct the flux toward increased precursor supply for better or overproduction of the amino acid. In branching amino acid biosynthetic pathways, weakening the competing branches to direct the available precursors and net carbon flux toward the overproduction of amino acids. The pyruvate node of the TCA cycle has been engineered for increased precursor supply for lysine, glutamate. 

Keywords Anaplerotic pathways Corynebacterium glutamicum Glutamate Metabolic engineering NCgll221 OdhI 2-Oxoglutarate dehydrogenase complex... 

Fig. 14.1 The biosynthesis pathway of L-threonine. The pathway consists of centeral metabolic pathways and the threonine terminal pathways. The centeral metabolic pathways involve glycolysis, phosphate pentose pathway, TCA cycle and anaplerotic pathways. The threonine terminal pathway consists of five enzymetic steps. The first, third, and fourth reactions are catalyzed by the three key enzymes aspartate kinase, homoserine dehydrogenase, tmd homoserine kinase, respectively. There are four competing pathways that affect the biosynthesis of L-threonine, leading to formation of L-lysine, L-metMonine, L-isoleucdne, and glycine...

L-threonine biosynthesis involves centeral metabolism including glycolysis, pentose phosphate pathway, TCA cycle and anaplerotic pathways between glycolysis and TCA cycle, prior to its terminal pathway (Fig. 14.1). 

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