Ornithine-delta-Transaminase Heterogeneity and Regulation. Sequential Expression of the "Liver" and "Kidney" Enzyme Forms during the HeLa Cell Cycle

Abstract

In previous work it has been shown that end‐product regulation of ornithine‐δ‐transaminase in liver and kidney is mediated by different amino acids. It is now described that the enzyme purified from liver has different properties from that obtained from kidney with regards to temperature optimum, rate of heat inactivation and Kmvalues. In HeLa cells grown in suspension and synchronized with thymidine, the “liver” form of ornithine‐δ‐transaminase appears in the S phase, while the “kidney” form of ornithine‐δ‐transaminase appears in the G1 phase. In the G2 phase there seems to be some mixing of the two enzyme forms. These data and reciprocal oscillation of proline content per cell and ornithine‐δ‐transaminase activity in the M and G1 phases suggest that only in these stages of the cell cycle the enzyme is subjected to the same type of regulation as in kidney.

Participation of ornithine aminotransferase in the synthesis and catabolism of ornithine in mice. Studies using gabaculine and arginine deprivation

“…than the rat, whereas renal or hepatic contents are similar or lower respectively [37]. Nutritional and hormonal factors affect this activity in the intestine and in other organs differently ( [42]; E. Alonso & V. Rubio, results not shown), and even distinct tissue-specific isoenzymic forms of OAT have been postulated [43]. All this supports the specialization of OAT in the intestine for ornithine synthesis, and in other organs for ornithine catabolism.…”

“…In many respects this cycle resembles that proposed by Haussinger et al [44] for hydrolysis and synthesis of glutamine by periportal and perivenous hepatocytes respectively. The cycle for ornithine is peculiar, however, in that the same enzyme (although perhaps in different isoenzymic forms [43]), OAT, is responsible for both the synthesis and the degradation of ornithine. That the synthesis de novo of ornithine is important, even with a normal dietary supply of arginine, is supported by the demonstration that Vol.…”

Ornithine Aminotransferase, an Important Glutamate-Metabolizing Enzyme at the Crossroads of Multiple Metabolic Pathways

“…A second isomorph is reported in the database (Uniprot P04181-2) with the first 138 residues missing. There has been a long controversy about differences between liver and kidney OAT, some studies suggesting the existence of different isozymes [45,46] and distinct physicochemical properties [41]. However, other researchers have found no evidence for any difference between the liver, kidney and small intestine forms of rat OAT [18,47].…”

Role of Thyroxine in the Postnatal Development of Rat Hepatic Tryptophan Oxygenase and Ornithine Aminotransferase

“…The induction of ornithine aminotransferase by triiodothyronine in the adult kidney is due to increased ornithine aminotransferase mRNA levels (25). This may not be the mechanism of action in the developing liver because liver and kidney ornithine aminotransferase enzymes are nonidentical (26,27) and are induced by different stimuli (28). Moreover, the ornithine aminotransferase activity of infant and adult livers responds differently to glucocorticoids, the former being reliably increased (8,13) and the latter being either unaffected (8,13,28) or reduced (29).…”