Glutamine metabolism in bone.
Evidence is provided for the utilization of glutamine by calvaria and compact bone of rat. Glutamine was actively transported into calvaria, principally by sodium-dependent mechanisms; its uptake was significantly inhibited by neutral amino acids (alanine, proline, serine, asparagine) and glutamine analogs (L-glutamate-gamma-hydroxamate, albizziin). Glutamine was degraded to ammonia and glutamate by phosphate-dependent glutaminase, a mitochondrial enzyme present in both calvaria and compact bone. The enzyme exhibited an apparent Kmgln of 2.35 mM, a KactPO4 of 25 mM, and a broad pH optimum (7.5-9.5). It was inactivated by incubation of intact calvaria or bone homogenates with the glutamine analogs 6-diazo-5-oxo-L-norleucine (DON) and a 2-amino-4-oxo-5-chloropentanoic acid (chloroketone). Such treatment also severely inhibited (greater than 95%) both ammonia and 14CO2 formation from [U-14C]glutamine. Glutamate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities were measured in bone. Amino-oxyacetate, an aminotransferase inhibitor, inhibited 14CO2 formation from [U-14C]glutamine. The data indicate that glutamine can serve as a precursor of ammonia, glutamate, other amino acids (alanine, aspartate, ornithine, proline) and carbon dioxide in bone and that phosphate-dependent glutaminase, transaminases, and citric acid cycle activity contribute to the observed metabolism.
D000596:Amino Acids / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005972:Glutaminase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D010710:Phosphates / Q000494:pharmacology; D051381:Rats; D012886:Skull; D012964:Sodium / Q000494:pharmacology; D000637:Transaminases / Q000378:metabolism
D000596:Amino Acids; D005971:Glutamates; D010710:Phosphates; D005973:Glutamine; D002245:Carbon Dioxide; D018698:Glutamic Acid; D000641:Ammonia; D012964:Sodium; D000637:Transaminases; D005972:Glutaminase