Glutamate catabolism

This chapter focuses initially on the catabolism of the amino acids. Aminotransferases can be used to catalyse the first step in the breakdown of nearly all of the amino acids. Lysine catabolism, in contrast, does not begin with an aminotrans-feraseamino acids can be catabolized via more than one pathway. Glutamate catabolism, for example, can begin by reactions catalyzed by glutamate oxaloacetate aminotransferase or glutamate dehydrogenase. 

The nitrogen source in the medium is the amino add glutamate. There are several cations K Mn2, Cn2, Zn2, Mg2, Co2, Fe2, Ca2 Mo6. Phosphate (POi") is the major anionic component. Fumaric add is a TCA cycle intermediate and may improve metabolic balance through the catabolic pathways and oxidation through the TCA cyde. Peptone may improve growth through the provision of growth factors (amino acids, vitamins, nudeotides). 

Figure 28-8. Biosynthesis of proline from glutamate by reversal of reactions of proline catabolism.

There is no associated impairment of hydroxyprohne catabolism. The metabolic block in type II hyperpro-linemia is at glutamate-7-semiaIdeliyde dehydrogenase, which also functions in hydroxyprohne catabolism. Both proline and hydroxyprohne catabohsm thus are affected and A -pyrroline-3-hydroxy-5-carboxylate (see Figure 30-10) is excreted. 

Alanine. Transamination of alanine forms pyruvate. Perhaps for the reason advanced under glutamate and aspartate catabolism, there is no known metabolic defect of alanine catabolism. Cysteine. Cystine is first reduced to cysteine by cystine reductase (Figure 30-7). Two different pathways then convert cysteine to pyruvate (Figure 30-8). 

Figure 30-3. Top Catabolism of proline. Numerals indicate sites of the metabolic defects in type I and type II hyper-prolinemias. Bottom Catabolism of arginine. Glutamate-y-semialdehyde forms a-ketoglutarate as shown above. , site of the metabolic defect in hyperargininemia.

Figure 30-12. Intermediates in tyrosine catabolism. Carbons are numbered to emphasize their ultimate fate. (a-KG, a-ketoglutarate Glu, glutamate PLP, pyridoxal phosphate.) Circled numerals represent the probable sites of the metabolic defects in type II tyrosinemia neonatal tyrosinemia alkaptonuria and 0 type I tyrosinemia, or tyrosinosis.

The reaction shown in Figure 8.6 is also important in the liver where glutamate dehydrogenase is involved in the catabolism of amino acids and the entry of nitrogen into the urea cycle, as explained in Chapter 6. 

The mechanism of action of valproate is complex and still the subject of uncertainty. The drug appears to act by enhancing GABAergic function. Thus it increases GABA release, inhibits catabolism and increases the density of GABA-B receptors in the brain. There is also evidence that it increases the sensitivity of GABA receptors to the action of the inhibitory transmitter. Other actions that may contribute to its therapeutic effects include a decrease in dopamine turnover, a decrease in the activity of the NMDA-glutamate receptors and also a decrease in the concentration of... 

The reaction involves formation of an imine through reaction of ammonia with the ketone, followed by reduction of this imine (see Section 7.7.1). As we noted earlier (see Section 15.1.1), nicotinamide coenzymes may also participate in imine reductions as well as aldehyde/ketone reductions, further emphasizing the imine-carbonyl analogy (see Section 7.7.1). The reverse reaction, removal of ammonia from glutamate, is also of importance in amino acid catabolism. 

This pathway is the hub of intermediary metabolism. Four- and five-carbon end products of many catabolic processes feed into the cycle to serve as fuels. Oxaloac-etate and a-ketoglutarate, for example, are produced from aspartate and glutamate, respectively, when proteins are degraded. Under some metabolic circumstances, intermediates are drawn out of the cycle to be used as precursors in a variety of biosynthetic pathways. 

An early step in the catabolism of amino acids is the separation of the amino group from the carbon skeleton. In most cases, the amino group is transferred to a-ketoglutarate to form glutamate. This transamination reaction requires the coenzyme pyridoxal phosphate. 

FIGURE 18-26 Catabolic pathways for arginine, histidine, glutamate, glutamine, and proline. These amino acids are converted to a-ketoglutarate. The numbered steps in the histidine pathway are catalyzed by histidine ammonia lyase, urocanate hydratase, imida-zolonepropionase, and glutamate formimino transferase. 

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