Disorders of glutamate metabolism.
The significant role the amino acid glutamate assumes in a number of fundamental metabolic pathways is becoming better understood. As a central junction for interchange of amino nitrogen, glutamate facilitates both amino acid synthesis and degradation. In the liver, glutamate is the terminus for release of ammonia from amino acids, and the intrahepatic concentration of glutamate modulates the rate of ammonia detoxification into urea. In pancreatic beta-cells, oxidation of glutamate mediates amino acid-stimulated insulin secretion. In the central nervous system, glutamate serves as an excitatory neurotransmittor. Glutamate is also the precursor of the inhibitory neurotransmittor GABA, as well as glutamine, a potential mediator of hyperammonemic neurotoxicity. The recent identification of a novel form of congenital hyperinsulinism associated with asymptomatic hyperammonemia assigns glutamate oxidation by glutamate dehydrogenase a more important role than previously recognized in beta-cell insulin secretion and hepatic and CNS ammonia detoxification. Disruptions of glutamate metabolism have been implicated in other clinical disorders, such as pyridoxine-dependent seizures, confirming the importance of intact glutamate metabolism. This article will review glutamate metabolism and clinical disorders associated with disrupted glutamate metabolism.
Kelly
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Division of Endocrinology, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania Medical School, 19104, USA.
Stanley
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CA
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000123:Acetyltransferases / Q000378:metabolism; D051046:Amino-Acid N-Acetyltransferase; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001928:Brain Diseases, Metabolic / Q000150:complications / Q000201:enzymology / Q000378:metabolism*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005969:Glutamate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D022124:Hyperammonemia / Q000378:metabolism; D007003:Hypoglycemia / Q000378:metabolism; D007223:Infant; D008099:Liver / Q000378:metabolism; D008297:Male; D009584:Nitrogen / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics; D011736:Pyridoxine / Q000378:metabolism; D012640:Seizures / Q000209:etiology; D014508:Urea / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics
D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; C421009:GluD protein, Corynebacterium glutamicum; D018698:Glutamic Acid; D014508:Urea; D005969:Glutamate Dehydrogenase; D000123:Acetyltransferases; D051046:Amino-Acid N-Acetyltransferase; C494874:NAGS protein, human; D011736:Pyridoxine; D009584:Nitrogen