Glutamic anaplerotic reactions

Pyruvate, from glycolysis of glucose, is carboxylated to oxaloacetate or oxidized to acetyl-CoA. These metabolites enter the Krebs cycle, are metabolized to a-ketoglutarate and oxaloacetate, then transaminated to aspartate or glutamate. Asn, Gin, and Pro are synthesized from Asp or Glu. The cycle replenishes intermediates via the anaplerotic reactions (e.g., car-boxylation of pyruvate to form oxaloacetate). 

Ornithine is required to maintain the urea cycle. Conversion of glutamate to ornithine via glutamate semialdehyde is therefore an anaplerotic reaction. Melatonin is a compound synthesized from serotonin. It has a function in the circadian rhythm activity and has nothing to do with intracellular protein degradation. 

Glutamate dehydrogenase catalyzes the anaplerotic reaction below (see here also) ... 

Aspartate, like glutamate, is an excitatory neurotransmitter, but it functions in far fewer pathways. It is synthesized from the TCA cycle intermediate oxaloacetate via transamination reactions. Like glutamate synthesis, aspartate synthesis uses oxaloacetate that must be replaced through anaplerotic reactions. Aspartate cannot pass through the blood-brain barrier. 

In addition to the carboxylation of pyruvate, there are other anaplerotic reactions that help to maintain appropriate levels of oxaloacetate. For example, the respective amino groups of glutamate and aspartate can be removed to yield the corresponding a-keto acids. How can these a-keto acids be used to replenish oxaloacetate levels ... 

The Importance of Anaplerotic Reactions in Glutamic Acid Production by Corynebacterium Glutamicum... 

Analyses of Importance of Anaplerotic Reactions During Glutamate Overproduction Based on "C Metabolic Flux Analysis... 

For glutamate production, a balanced supply of acetyl-CoA and oxaloacetate is important to proceed TCA cycle reactions toward 2-oxoglutarate, because it is a substrate for glutamate biosynthesis catalyzed by GDH. In particular, anaplerotic reactions, which supply oxaloacetate from the glycolytic intermediates, are caudal. C. glutamicum possesses two enzymes for anaplerotic reactions phosphoenolpyru-vate carboxylase (PEPC) encoded by ppc and pyruvate carboxylase (PC) encoded by pyc (Bormann et al. 1992 Eikmanns et al. 1995 O Regan et al. 1989 Peters-Wendisch et al. 1998). PC requires biotin as a cofactor for its activity. MFA was conducted to understand the role of these anaplerotic reactions in glutamate production. 

For the production of glutamic acid, anaplerotic reactions are important to supply oxaloacetate to the TC A cycle for the latter to proceed. C. glutamicum possesses the following two anaplerotic reactions, catalyzed by phosphoenolpyruvate carboxylase (PPC) and pyruvate carboxylase (PC) [63,64] ... 

PC requires biotin for its activity as a coenzyme. In the presence of biotin, disruption of ppc, which encodes PPC, abolished glutamic acid production, but disruption of pyc, which encodes PC, did not affect glutamic acid production [65]. Moreover, under Tween 40 addition conditions, genetic and metabolic analyses indicted that the reaction catalyzed by PC was important for glutamic acid overproduction [12,66]. Metabolic analysis to investigate the roles of anaplerotic reactions in glutamic acid production is described in Section 11.4.2. 

Use of C-MFA to Investigate the Importance of Anaplerotic Reactions to Glutamic Acid Production... 

The anaplerotic reactions provide another target for metabohc engineering to improve glutamic acid production by C. utamicum. Peters-Wendisch et al. 

Figure 4-12. Anaplerotic and biosynthetic reactions involving TCA cycle intermediates. Synthetic reactions that form fatty acids and glucose are indicated by broken lines. PC = pyruvate carboxylase GDH= glutamate dehydrogenase.

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