Metabolites glutamine

The metabolites glutamine and glucose are the main substrates of mammalian cell culture. Nevertheless, even if they are not limited in oxygen, proliferating mammalian cells do not completely oxidize their main substrates to CO2 but produce the fermentative product lactate. This observation, termed Warburg effect, is hypothesized to be a result of the needs of proliferating cells for precursor metabolites instead of maximum ATP formation via complete... 

Another toxic metabolite is ammonia. It is released by spontaneous decomposition of glutamine and to a far greater extend produced as a metabolite in... 

Berl, S., Nicklas, W. J. and Clarke, D. D. Compartmentation of citric acid cycle metabolism in brain labelling of glutamate, glutamine, aspartate and gaba by several radioactive tracer metabolites. J. Neurochem. 17 1009-1015, 1970. 

The subtitle of this book, "The Basis for the Genetotrophic Concept," reflects Williams s major interest in disorders that involve interactions between heredity (geneto) and nutrition (trophic). A genetotrophic disease is one caused by a genetic need for unusual amounts of one or more nutrients that are not found in diets which are adequate for most individuals. This broad concept includes genetic needs for an exogenous supply of a metabolite normally produced internally in adequate amounts, such as carnitine or glutamine. 

CSF amino acids do not show an important age dependence (Table 2.1.7). Levels of most amino acids in the CSF are much lower than in the plasma, the exception being glutamine. The low CSF values bear a certain analytical risk a traumatic lumbar puncture will result in the presence of small amounts of blood in the CSF. This readily influences the CSF amino acid levels and should be interpreted with care. In contrast with some of the neurotransmitter metabolites, no ventral/dorsal gradient for the amino acid is observed. 

All amino acids are derived from intermediates in glycolysis, the citric acid cycle, or the pentose phosphate pathway (Fig. 22-9). Nitrogen enters these pathways by way of glutamate and glutamine. Some pathways are simple, others are not. Ten of the amino acids are just one or several steps removed from the common metabolite from which they are derived. The biosynthetic pathways for others, such as the aromatic amino acids, are more complex. 

Molecules with structures as diverse as carbamoyl-phosphate, tryptophan, and cytidine triphosphate are feedback inhibitors of the E. coli glutamine synthase. The feedback inhibition is cumulative, with each metabolite exerting a partial inhibition on the enzyme. Why would complete inhibition of the glutamine synthase by a single metabolite be metaboli-cally unsound ... 

When injected, azathioprine (Imuran) is rapidly converted to 6-mercaptopurine. The half-life of azathioprine after intravenous injection is 10 to 20 min, and that of 6-mercaptopurine is somewhat longer. The cytotoxic activity of these thiopurines is due to the conversion of mercaptopurine to 6-thiouric acid, a noncarcinostatic metabolite. This action is thought to block the excess synthesis of inosinic acid from its precursors, glutamine and phosphoribosylpyrophosphate. In addition, unlike cyclophosphamide, azathioprine is a potent anti-inflammatory substance that can cause a reduction in the number of monocytes and neutrophils at inflammatory sites. Antibody responses are also inhibited by azathioprine. Studies in humans have shown that azathioprine decreases the y-globulin and antibody levels, thus influencing IgG rather than IgM production. This makes azathioprine an effective immunosuppressant in the early phases of immune responses. It is less effective or completely ineffective in altering either the effector phase or already established reactivities. 

Jl. Jepson, J. B., Indolylacetyl-glutamine and other indole metabolites in Hartnup disease. Biochem. ]. 64, 14P (1956). 

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