The uptake of ornithine and lysine by isolated hepatocytes and fibroblasts

Metoki, K.; Hommes, F. A.

doi:10.1016/0020-711x(84)90197-6

Cited by 12 publications

(4 citation statements)

References 14 publications

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“…However, as demonstrated by White & Christensen (1982), system y+ contributes little to the flux of cationic amino acids in the hepatocytes and a nonsaturable transport component exists whose contribution seems important relative to the system y+. This diffusional component of Om transport has been demonstrated in Ehrlichcell plasma-membrane vesicles (Medina et al 1991) as well as in hepatocytes (Metoki & Hommes, 1984), and its importance increases with increasing Orn concentrations (Metoki & Hommes, 1984). Since our experiments were performed at high Om and Arg concentrations (4 mM), the uptake of these two compounds could tentatively be attributed to this non-saturable transport.…”

Section: Discussionsupporting

confidence: 59%

Metabolism of ornithine, α-ketoglutarate and arginine in isolated perfused rat liver

et al. 1995

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Omithine (Om; a-ketoglutarate (aKG) salt) and arginine (Arg) supplementation of enteral diets has been advocated in the treatment of hypercatabolism of trauma patients, but both compounds are subject to extensive hepatic metabolism. To compare the metabolism of these two compounds and to evaluate the possible influence of the aKG moiety, livers were perfused with aKG, Om, ornithine a-ketoglutarate (OKG) or Arg (n 6 in each group) for 1 h. Arg uptake was nearly fourfold higher than Om uptake (690 (SD 162) v. 178 (SD 30) nmol/min per g liver), and Om uptake was not modified by aKG. Om was totally metabolized by the liver, whereas Arg led to Om release (408 (SD 159) nmol/min per g liver) and a threefold stimulation of urea production (Arg 1-44 (SD 0%) Y. Om 0.45 (SD 0.09) pmol/min per g liver). aKC alone only increased hepatic aspartate uptake but, when essociated with Om as OKG, it led to an increase in glutamate release and in proline content in the liver and to a decrease in proline uptake. From these findings we conclude that (1) Arg load is extensively metabolized by the liver, inducing urea production, (2) in enteral use, Om supplementation appears preferable to Arg as it is less ureogenic (as also recently demonstrated in viva in stressed rats receiving isomolar amounts of Arg and Om), (3) the liver participates in the OrwlKG metabolic interaction, mostly in proline metabolism, which occurs in the splanchnic area.Arginine: a-Ketoglutarate: Liver: Ornithine Nutritional support has emerged as an important component of the treatment of severely ill patients, but there is a need for qualitative improvements through the use of compounds which can modulate protein turnover. In this respect, ornithine (Om), as its a-ketoglutarate (aKG) salt, and arginine (Arg) are promising candidates and several studies have provided firm evidence that supplementation of enteral or parenteral nutrition with ornithine

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Section: Discussionsupporting

confidence: 59%

Metabolism of ornithine, α-ketoglutarate and arginine in isolated perfused rat liver

et al. 1995

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“…Therefore, neither diffusional uptake of arginine nor, alternatively, uptake with a KM greater than 2 mM appear to be of physiological significance. A similar non-saturable component was found for uptake of lysine and other amino acids in astrocytes in suspension (Hannuniemi and Oja, 1981), but also for cationic amino acids in fibroblasts, hepatocytes, and two renal epithelial cell lines (Metoki and Hommes, 1984;Sepulveda and Pearson, 1985;White et al, 1982).…”

Section: Discussionmentioning

confidence: 64%

“…In accordance with this, arginine transport in the cultured glial cells was not dependent on the concentration of extracellular Na+ and uptake of arginine was strongly inhibited by an excess of lysine or ornithine. Similar inhibition was found, e.g., in hepatocytes and fibroblasts (Metoki and Hommes, 1984), but also in brain slices (Sayegh and Lajtha, 1991;Sershen and Lajtha, 1979). Some lack of specificity of system "y+" in the glial cells can be inferred from the fact that other amino acids with nitrogen in the side chain (histidine, asparagine, and glutamine) inhibited arginine transport to a considerable extent.…”

Section: Discussionmentioning

confidence: 65%

Transport of L‐arginine in cultured glial cells

Schmidlin

Wiesinger

1994

Glia

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Uptake of radiolabelled L-arginine was studied in four different kinds of glial cultures, in astroglia-rich primary cultures derived from neonatal rat and mouse brains, in pure murine astrocyte cultures, and in rat glioma cells C6-BU-1. A saturable component of uptake was found in all cases with KM values between 15 and 35 microM and Vmax values between 0.8 and 2.5 nmol.min-1.(mg protein)-1. In addition, in all cell types a non-saturable component dominated total uptake at high concentrations of extracellular arginine. Rates of uptake of arginine were not affected when Na+ or Cl- were absent from the incubation buffer. Carrier-mediated uptake of arginine was reduced by depolarizing concentrations of K+ and strongly inhibited by an excess of lysine or ornithine. Histidine, asparagine, glutamine, citrulline, creatine, NG-nitro-L-arginine, NG-monomethyl-L-arginine, or L-canavanine inhibited L-arginine transport to various degrees. Uptake of arginine was not reduced in the presence of serine or alanine cysteic acid, N-methyl-alpha-aminoisobutyric acid, or 2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid. Rates of uptake of arginine were increased when cells had been preloaded with lysine. Preincubation of primary cultures, but not glioma cells, with bacterial lipopolysaccharide stimulated transport of arginine by increasing the Vmax value of uptake. This stimulation was dependent on protein synthesis. The results suggest that, at physiological concentrations, arginine is taken up into the glial cells with the help of the transport system "y+" for basic amino acids. In glial primary cultures, uptake of arginine appears to be regulated by compounds which also exert influence on nitric oxide synthesis.

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“…Cultured cells or tissues have a n active amino acid uptake system which cotransports ornithine, arginine, and lysine (White and Christensen, 1982). In addition to this active, saturable amino acid uptake system, there is a non-saturable system for the uptake of ornithine which has been observed in fibroblasts (Metoki and Hommes, 1984). TPA might directly or indirectly have stimulated these uptake systems leading to increased intracellular ornithine levels.…”

Section: Discussionmentioning

confidence: 99%

The level of substrate ornithine can alter polyamine‐dependent DNA synthesis following phorbolester stimulation of cultured hepatoma cells

Byus

1991

Journal Cellular Physiology

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Although the precise intracellular function(s) of the polyamines remain incompletely defined, a myraid of evidence now shows that the polyamines must accumulate or be maintained at a specific intracellular concentration in order for all mammalian cells to grow or divide. The initial step in polyamine biosynthesis normally involves the decarboxylation of ornithine by the enzyme ornithine decarboxylase (ODCase E.C. 4.1.1.17) to yield putrescine. Increases in the steady-state level of intracellular ornithine have been reported to markedly alter the accumulation of the polyamines following stimulation of Reuber H35 Hepatoma cells with 12-O-tetradecanoylphorbol-beta-acetate (TPA) in the presence of serum (Wu and Byus: (Biochem. Biophys. Acta 804:89-99, 1984); Wu et al.: (Cancer Res. 41:3384-3391, 1981). We wished to determine whether or not incubation of H35 hepatoma cells with exogenous ornithine would result in a stimulation of DNA synthesis following treatment with the mitogens TPA and insulin. For these studies, H35 cells were maintained under serum-free conditions for 2-3 days in order to obtain synchronous cultures suitable for analysis of the level of DNA synthesis. Cultures treated in this manner were highly viable, maintained similar growth rates, and possessed the equivalent levels of intracellular ornithine and polyamines as the serum-containing cultures. Arginine levels, however, were approximately twofold higher following culture under serum-restricted conditions for 3 days. The addition of exogenous ornithine (0.5 mM) was accompanied by a 4-5-fold increase in intracellular steady-state ornithine levels and by a 6-8-fold increase in the presence of TPA and ornithine. In a manner identical to the serum-containing cultures (Wu and Byus (1984] the addition of TPA and exogenous ornithine to the serum-free cells caused a dose-dependent increase in intracellular putrescine (up to 5-fold) and a concomitant decrease in ODC activity in comparison to stimulation with TPA alone. The addition of TPA led to a 3-5-fold increase in the incorporation of tritiated thymidine into DNA. In the presence of exogenous ornithine, TPA-induced DNA synthesis was further stimulated more than twofold in a dose-dependent manner. Insulin (10(-10)-10(-8) M) proved to be more efficacious as a mitogen in the H35 cells and led to greater stimulation of DNA synthesis than TPA. Insulin alone also resulted in a higher steady-state level of ornithine and putrescine in comparison with TPA alone.(ABSTRACT TRUNCATED AT 250 WORDS)

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The uptake of ornithine and lysine by isolated hepatocytes and fibroblasts

Cited by 12 publications

References 14 publications

Metabolism of ornithine, α-ketoglutarate and arginine in isolated perfused rat liver

Metabolism of ornithine, α-ketoglutarate and arginine in isolated perfused rat liver

Transport of L‐arginine in cultured glial cells

The level of substrate ornithine can alter polyamine‐dependent DNA synthesis following phorbolester stimulation of cultured hepatoma cells

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