The aliphatic polyamines, putrescine, spermidine, and spermine, appear to play an important role in many forms of rapid growth including embryonic, regenerative, hormone-induced, and neoplastic. While the exact biochemical function of polyamines is unclear, current evidence suggests they are probably involved in the biosynthesis and accumulation of nucleic acids and proteins. Increased levels of polyamines and their biosynthetic enzymes are associated with augmented kidney growth stimulated by renal mass extirpation, as well as by various hormones, toxins, and carcinogens. These observations are reviewed and additional data is provided pertaining to alterations in polyamine metabolism during compensatory renal growth following unilateral nephrectomy (uni). To further explore the effect of growth stimuli on renal polyamine synthesis, an in vitro system was employed which previously provided evidence for a circulating renal growth factor after unilateral nephrectomy. These in vitro observations underscore the rapid inducibility of ornithine decarboxylase, the rate limiting enzyme for polyamine biosynthesis; illustrate the association of polyamine and nucleic acid synthesis during enhanced kidney growth; and support the existence of a circulating renal growth regulator which apparently contributes to compensatory responses following loss of functional renal parenchyma.

Intramitochondrial glutamate removal through deamination may regulate renal ammoniagenesis from glutamine. However, little information is available to determine if there is a strong association between glutamine deamidation and the removal within mitochondria of the glutamate subsequently formed after deamidation. Using rat renal mitochondria, we found that ammonia production, glutamate appearance, and amide nitrogen disappearance were near equal aerobically and anaerobically, when no ADP-generating system was present. Whan an ADP-generating system was added (ATP alone, ATP + malonate, or ATP+ 2,4 DNP), more ammonia was formed aerobically from glutamine. Additionally, less glutamate appeared even though more amide nitrogen disappeared. Intramitochondrial concentrations of glutamate decreased. When pyruvate and α-ketoglutarate were added to the system, ammoniagenesis, deamidation, and deamination decreased; while glutamate built up in both the medium and mitochondria. In our mitochondrial system, we found a significantly positive correlation between glutamate deamination and glutamine deamidation, between glutamate accumulation and intramitochondrial glutamate concentrations; and a significantly negative correlation between glutamate deamination and glutamate accumulation, between glutamine deamidation and intramitochondrial glutamate concentrations, and between glutamate deamination and glutamate accumulation. We conclude that there is a biochemical relationship between glutamine deamidation and deamination of the glutamate subsequently formed. We propose that increased deamination lowers mitochondrial concentrations of glutamate and increases deamidation. In contrast, slowing deamination increases mitochondrial concentrations of glutamate and decreases deamidation.

Renal slices from 191 rats in various states of acid-base balance were investigated for their ability to produce ammonia from both glutamine and glutamate. Under a variety of conditions, in three different type studies, a significantly similar correlation existed between ammonia adaptation from glutamine and glutamate. This relationship was maintained during acute and chronic acidosis and during alkalotic inhibition of renal ammoniagenesis. We conclude from our findings that ammonia adaptation in rats secondary to acute and chronic acidosis is similar, although incomplete during acute acidosis. Our results further support the hypothesis that the rate of glutamate deamination is a major mechanism for overall renal ammonia adaptation in rats during acid-base changes.

The concentration of renal 2-oxoglutarate has been proposed as an important regulator of ammoniagenesis in dog kidneys. In the present study, canine kidney slices produced less ammonia from glutamine and glutamate when 2-oxoglutarate was present in the incubation medium. However, the addition of arsenite, a metabolic blocker known to block 2-oxoglutarate metabolism and lead to its accumulation, overcame 2-oxoglutarate inhibition of ammoniagenesis when glutamine and glutamate were the ammonia precursors. Therefore, metabolism of 2-oxoglutarate, rather than its concentration, governed ammonia production from glutamine and glutamate in incubating dog renal tissue. In contrast to the results with 2-oxoglutarate, inhibition of glutamine ammoniagenesis by glutamate was not overcome by arsenite. The results suggest that renal ammonia adaptation in acidotic dogs cannot be ascribed to a theory based upon 2-oxoglutarate concentrations controlling the direction of the glutamate dehydrogenase pathway (GDH), decreasing glutamine transport, or directly inhibiting GDH enzyme activity.