Early events in the initiation of ammonia formation in kidney.
Experiments were designed to examine the early events in the initiation of glutamate deamination in kidney. Perfused kidneys from methionine sulfoximine-treated rats formed ammonia from [15N]glutamate via the purine nucleotide cycle. The turnover of the 6-amino group of adenine nucleotides to yield ammonia occurred at the rate of 0.30 mumol/g of kidney/min. This rate is 3-4 times larger than in liver and is in agreement with published rates of the purine nucleotide cycle in kidney. The addition of 0.1 mM fluorocitrate to glutamate perfusions stimulated ammonia formation 3 1/2-fold. The turnover of the 6-amino group of adenine nucleotides increased during the first 5 min after adding fluorocitrate to form ammonia predominately from tissue glutamate and aspartate. This turnover correlates with a 3 1/2-fold increase in kidney tissue IMP levels. As the ATP/ADP ratio fell the purine nucleotide cycle was inhibited and glutamate dehydrogenase was stimulated to form ammonia stoichiometric with glutamate taken up from the perfusate. Ammonia formation via glutamate dehydrogenase occurred at a rate of 1.0 mumol/g of kidney/min. Fluorocitrate completely blocked ammonia formation from aspartate in perfusions. The perfused kidney formed ammonia from aspartate via the purine nucleotide cycle at a rate of 1.0 mumol/g of kidney/min. The results indicate a discrete role for aspartate in renal metabolism. Ammonia formation via the purine nucleotide cycle can occur at significant rates and equal to the rate of ammonia formation from glutamate via glutamate dehydrogenase.
D000596:Amino Acids / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D002951:Citrates / Q000378:metabolism / Q000494:pharmacology; D019343:Citric Acid; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D002951:Citrates; D005971:Glutamates; D007773:Lactates; D019343:Citric Acid; D019344:Lactic Acid; C007744:fluorocitrate; D018698:Glutamic Acid; D000641:Ammonia