Reduced citrulline availability by OTC deficiency in mice is related to reduced nitric oxide production

The amino acid arginine is the sole precursor for nitric oxide (NO) synthesis. We recently demonstrated that an acute reduction of circulating arginine does not compromise basal or LPS-inducible NO production in mice. In the present study, we investigated the importance of citrulline availability in ornithine transcarbamoylase-deficient spf(ash) (OTCD) mice on NO production, using stable isotope techniques and C57BL6/J (wild-type) mice controls. Plasma amino acids and tracer-to-tracee ratios were measured by LC-MS. NO production was measured as the in vivo conversion of l-[guanidino-(15)N(2)]arginine to l-[guanidine-(15)N]citrulline; de novo arginine production was measured as conversion of l-[ureido-(13)C-5,5-(2)H(2)]citrulline to l-[guanidino-(13)C-5,5-(2)H(2)]arginine. Protein metabolism was measured using l-[ring-(2)H(5)]phenylalanine and l-[ring-(2)H(2)]tyrosine. OTC deficiency caused a reduction of systemic citrulline concentration and production to 30-50% (P < 0.001), reduced de novo arginine production (P < 0.05), reduced whole-body NO production to 50% (P < 0.005), and increased net protein breakdown by a factor of 2-4 (P < 0.001). NO production was twofold higher in female than in male OTCD mice in agreement with the X-linked location of the OTC gene. In response to LPS treatment (10 mg/kg ip), circulating arginine increased in all groups (P < 0.001), and NO production was no longer affected by the OTC deficiency due to increased net protein breakdown as a source for arginine. Our study shows that reduced citrulline availability is related to reduced basal NO production via reduced de novo arginine production. Under basal conditions this is probably cNOS-mediated NO production. When sufficient arginine is available after LPS stimulated net protein breakdown, NO production is unaffected by OTC deficiency.     

Arginine,ornithine, and proline interconversion is dependent on small intestinal metabolism in neonatal pigs

We have previously shown that arginine deficiency is exacerbated by the removal of dietary proline in orally, but not parenterally, fed piglets. Therefore, we hypothesized that the net interconversions of proline, ornithine, and arginine primarily occur in the small intestine of neonatal piglets. Ten intragastrically fed piglets received either intraportal (IP) or intragastric (IG) primed, constant infusions of [guanido-(14)C]arginine and [U-(14)C]ornithine + [2,3-(3)H]proline. By infusing amino acid isotopes via the stomach compared with the portal vein, we isolated small intestinal first-pass metabolism in vivo. During IP infusion, fractional net conversions (%) from proline to ornithine (0), ornithine to arginine (11 +/- 6), and ornithine to proline (5 +/- 1) were lower (P < 0.05) than during IG infusion (39 +/- 8, 18 +/- 6, and 42 +/- 12, respectively); we speculate that these data are due to the localization of ornithine aminotransferase to the gut. The balance of these conversions indicated a large synthesis of arginine (70.0 micromol. kg(-1). h(-1)) by the gut, with a corresponding degradation of ornithine (70.8 micromol. kg(-1). h(-1)) and no change in proline balance. Gut synthesis of arginine from proline (48.1 micromol. kg(-1). h(-1)) was 50% of its requirement, whereas proline synthesis from arginine (33.0 micromol. kg(-1). h(-1)) amounted to 10% of its requirement. Overall, arginine synthesis is more dependent on the gut than proline synthesis. In situations in which gut metabolism is compromised, such as during parenteral nutrition or gastrointestinal disease, arginine and proline are individually indispensable because their biosyntheses are negligible.     

Incorporation of dl-[2-14C]ornithine and dl-[5-14C]arginine in milk constituents by the isolated lactating sheep udder

1. Lactating mammary glands of sheep were perfused for several hours in the presence of dl-[2-(14)C]ornithine or dl-[5-(14)C]arginine and received adequate quantities of acetate, glucose and amino acids. 2. In the [(14)C]ornithine experiment 1.4% of the casein and 1% of the expired carbon dioxide came from added ornithine; 96% of the total radioactivity in casein was recovered in proline; 13% of the proline of casein originated from plasma ornithine. 3. In this experiment the results of chemical degradation of proline of casein as well as relative specific activities in the isolated products are consistent with the view that ornithine is metabolized, by way of glutamic gamma-semialdehyde, to proline or glutamic acid. 4. In the [(14)C]arginine experiments 3% of the casein and 1% of the expired carbon dioxide came from arginine; 84% of the arginine and 9% of the proline of casein originated from plasma arginine. 5. In these experiments the relative specific activities of arginine, ornithine and proline in plasma are in agreement with the view that arginine is metabolized by way of ornithine to proline. The conversion of arginine into ornithine is probably catalysed by arginase, so that arginase in mammary tissue may be involved in the process of milk synthesis.     

A multitracer stable isotope quantification of the effects of arginine intake on whole body arginine metabolism in neonatal piglets

We have previously shown that deficient arginine intake increased the rate of endogenous arginine synthesis from proline. In this paper, we report in vivo quantification of the effects of arginine intake on total endogenous arginine synthesis, on the rates of conversion between arginine, citrulline, ornithine, and proline, and on nitric oxide synthesis. Male piglets, with gastric catheters for diet and isotope infusion and femoral vein catheters for blood sampling, received a complete diet for 2 days and then either a generous (+Arg; 1.80 g x kg(-1) x day(-1); n = 5) or deficient (-Arg; 0.20 g.kg(-1).day(-1); n = 5) arginine diet for 5 days. On day 7, piglets received a primed, constant infusion of [guanido-(15)N(2)]arginine, [ureido-(13)C;5,5-(2)H(2)]citrulline, [U-(13)C(5)]ornithine, and [(15)N;U-(13)C(5)]proline in an integrated study of the metabolism of arginine and its precursors. Arginine synthesis (micromol x kg(-1) x h(-1)) from both proline (+Arg: 42, -Arg: 74, pooled SE: 5) and citrulline (+Arg: 67, -Arg: 120; pooled SE: 15) were higher in piglets receiving the -Arg diet (P < 0.05); and for both diets proline accounted for approximately 60% of total endogenous arginine synthesis. The conversion of proline to citrulline (+Arg: 39, -Arg: 67, pooled SE: 6) was similar to the proline-to-arginine conversion, confirming that citrulline formation limits arginine synthesis from proline in piglets. Nitric oxide synthesis (micromol x kg(-1) x h(-1)), measured by the rate conversion of [guanido-(15)N(2)]arginine to [ureido-(15)N]citrulline, was greater in piglets receiving the +Arg diet (105) than in those receiving the -Arg diet (46, pooled SE: 10; P < 0.05). This multi-isotope method successfully allowed many aspects of arginine metabolism to be quantified simultaneously in vivo.     

Arginine synthesis is regulated by dietary arginine intake in the enterally fed neonatal piglet

Arginine is conditionally indispensable in the neonate, and its synthesis in the intestine is not sufficient to meet requirements. It is not known how neonatal endogenous arginine synthesis is regulated and the degree to which proline and glutamate are used as precursors. Primed, constant intraportal and intragastric infusions of L-[U-14C]proline and L-[3,4-3H]glutamate, and intragastric L-[guanido-14C]arginine were used to measure whole body and first-pass intestinal arginine synthesis in 10 neonatal piglets fed generous (1.80 g.kg(-1).day(-1)) or deficient (0.20 g.kg(-1).day(-1)) quantities of arginine for 5 days. Glutamate tracer was not detected in arginine, indicating a biologically insignificant conversion of <1% of arginine flux. Endogenous arginine synthesis from proline had obligatory (0.36 g.kg(-1).day(-1)) and maximal (0.68 g.kg(-1).day(-1)) levels (P < 0.05, pooled SE 0.05). Although first-pass gut metabolism is responsible for 42-63% of whole body arginine synthesis, the gut is incapable of upregulating proline to arginine conversion during arginine deficiency, compared with a more than threefold increase without first-pass gut metabolism. These data suggest that upregulation of proline-to-arginine conversion occurs via increased arterial extraction of proline by the gut or in nonintestinal tissues. This study demonstrates that dietary arginine is an important regulator of endogenous arginine synthesis in the neonatal piglet and that proline, but not glutamate, is an important precursor for arginine synthesis in the neonate.     

烧伤狗浆血游离氨基酸的动态变化

烧伤狗浆血游离氨基酸的动态变化黎君友,周幼勤,赖业馥,赵有,伊少杰ＳｅｑｕｅｎｔｉａｌＣｈａｎｇｅｓｉｎＰｌａｓｍａＦｒｅｅＡｍｉｎｏＡｃｉｄＣｏｎｃｅｎｔｒａｔｉｏｎｉｎＢｕｒｎｅｄＤｏｇｓ￥Ｌｉｊｕｎｙｏｎ;Ｚｈｏｕｙｏｕｑｉｎ;Ｌａｉｙｅｆｕ;...     

Metabolism of [14C]citrulline in the perfused sheep and goat udder

1. A lactating-sheep mammary gland was perfused for 12h in the presence of l-[2-(14)C]-citrulline and received adequate quantities of glucose, acetate and amino acids. Two lactating-goat udders were similarly perfused in the presence of either l-[carbamoyl-(14)C,-2-(14)C]citrulline or l-[carbamoyl-(14)C,1-(14)C]citrulline and l-[4-(3)H]arginine. 2. In these experiments, [(14)C]citrulline was substantially oxidized to CO(2) and converted into arginine and proline of casein. 3. The specific radioactivities of arginine, ornithine and proline of the plasma increased after passage through the udders, demonstrating that [(14)C]citrulline is metabolized by the mammary gland. 4. The presence of two unknown radioactive metabolites of [(14)C]citrulline was detected in the perfusate. These substances were not found after incubation in vitro of oxygenated blood in the presence of the radioactive precursor. 5. From these experiments, it is concluded that citrulline is metabolized in mammary tissue by way of arginine to urea, ornithine and proline.     

Comparison of the inhibitory effects of diverse amino acids and amino acid analogs on 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity in isolated epidermal cells

At a concentration of 1.25 mM, 14 amino acids were capable of inhibiting the induction of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in isolated epidermal cells. The greatest percentages of inhibition of TPA-induced epidermal ornithine decarboxylase activity were as follows: cysteine, 98%; tryptophan, 74%; methionine, 64%; phenylalanine, 51%; glycine, 44%; asparagine, 43%; glutamic acid, 42%; leucine, 40%; and arginine, 39%. These amino acid treatments did not alter the time- and concentration-response curves for induction of ornithine decarboxylase activity by TPA. Moreover, there was no difference between the rates at which [3H]arginine, [3H]leucine, [3H]phenylalanine, [3H]methionine, [3H]tryptophan and [14C]cysteine were taken up by freshly isolated epidermal cells or incorporated into epidermal proteins. Arginine, phenylalanine and methionine inhibited the induction of ornithine decarboxylase activity by the tumor promoter to degrees comparable to those elicited by their analogs canavanine and homoarginine, beta-2-thienyl-DL-alanine, and ethionine, respectively. These amino acids and amino acid analogs did not alter the overall rate of protein synthesis. In contrast, both the amino acids and their analogs increased the rates of proteolysis in isolated epidermal cells, an effect which correlated well with the abilities of these different compounds to inhibit TPA-induced ornithine decarboxylase activity. Moreover, both methionine and phenylalanine decreased the half-life and increased the rate of heat denaturation of the TPA-induced enzyme, a result identical to that obtained after treatment with the analogs ethionine and beta-2-thienyl-DL-alanine, respectively. Taken together, these results suggest that millimolar concentrations of exogenous amino acids might induce the synthesis of abnormal proteins and nonfunctional enzymes. Therefore, it is speculated that the uptake of unbalanced amounts of amino acids into the epidermal target cells might alter the stability and the ultrastructure of the TPA-stimulated enzyme just as the amino acid analogs do.     

Metabolism of Proline, Glutamate, and Ornithine in Proline Mutant Root Tips of Zea mays (L.)

In excised pro_1-1 mutant and corresponding normal type roots of Zea mays L. the uptake and interconversion of [¹⁴C]proline, [¹⁴C]glutamic acid, [¹⁴C]glutamine, and [¹⁴C]ornithine and their utilization for protein synthesis was measured with the intention of finding an explanation for the proline requirement of the mutant. Uptake of these four amino acids, with the exception of proline, was the same in mutant and normal roots, but utilization differed. Higher than normal utilization rates for proline and glutamic acid were noted in mutant roots leading to increased CO₂ production, free amino acid interconversion, and protein synthesis. Proline was synthesized from either glutamic acid (or glutamine) or ornithine in both mutant and normal roots; it did not accumulate but rather was used for protein synthesis. Ornithine was not a good precursor for proline in either system, but was preferentially converted to arginine and glutamine, particularly in mutant roots. The pro_1-1 mutant was thus not deficient in its ability to make proline. Based on these findings, and on the fact that ornithine, arginine, glutamic acid and aspartic acid are elevated as free amino acids in mutant roots, it is suggested that in the pro_1-1 mutant proline catabolism prevails over proline synthesis.     

Arginine catabolism in the cyanobacterium Synechocystis sp. Strain PCC 6803 involves the urea cycle and arginase pathway

Cells of the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 supplemented with micromolar concentrations of L-[(14)C]arginine took up, concentrated, and catabolized this amino acid. Metabolism of L-[(14)C]arginine generated a set of labeled amino acids that included argininosuccinate, citrulline, glutamate, glutamine, ornithine, and proline. Production of [(14)C]ornithine preceded that of [(14)C]citrulline, and the patterns of labeled amino acids were similar in cells incubated with L-[(14)C]ornithine, suggesting that the reaction of arginase, rendering ornithine and urea, is the main initial step in arginine catabolism. Ornithine followed two metabolic pathways: (i) conversion into citrulline, catalyzed by ornithine carbamoyltransferase, and then, with incorporation of aspartate, conversion into argininosuccinate, in a sort of urea cycle, and (ii) a sort of arginase pathway rendering glutamate (and glutamine) via Delta(1)pyrroline-5-carboxylate and proline. Consistently with the proposed metabolic scheme (i) an argF (ornithine carbamoyltransferase) insertional mutant was impaired in the production of [(14)C]citrulline from [(14)C]arginine; (ii) a proC (Delta(1)pyrroline-5-carboxylate reductase) insertional mutant was impaired in the production of [(14)C]proline, [(14)C]glutamate, and [(14)C]glutamine from [(14)C]arginine or [(14)C]ornithine; and (iii) a putA (proline oxidase) insertional mutant did not produce [(14)C]glutamate from L-[(14)C]arginine, L-[(14)C]ornithine, or L-[(14)C]proline. Mutation of two open reading frames (sll0228 and sll1077) putatively encoding proteins homologous to arginase indicated, however, that none of these proteins was responsible for the arginase activity detected in this cyanobacterium, and mutation of argD (N-acetylornithine aminotransferase) suggested that this transaminase is not important in the production of Delta(1)pyrroline-5-carboxylate from ornithine. The metabolic pathways proposed to explain [(14)C]arginine catabolism also provide a rationale for understanding how nitrogen is made available to the cell after mobilization of cyanophycin [multi-L-arginyl-poly(L-aspartic acid)], a reserve material unique to cyanobacteria.     

Nutrient uptake by Candida albicans: the influence of cell surface mannoproteins.

Numerous ultrastructural and biochemical analyses have been performed to characterize the cell wall composition and structure of Candida albicans. However, little investigation has focused on how subtle differences in cell wall structure influence the intracellular transport of amino acids and monosaccharides. In this study C. albicans 4918 and ATCC 10231 were grown in culture conditions capable of modifying surface mannoproteins and induced surface hydrophobic or hydrophilic yeast cell wall states. Subcultures of these hydrophobic and hydrophilic yeasts were subsequently incubated with one of seven L-[3H] amino acids: glycine, leucine, proline, serine, aspartic acid, lysine, or arginine. The transport of [3H] mannose and [3H] N-acetyl-D-glucosamine were also investigated. This study revealed significant strain differences (P < or = 0.05) between hydrophilic and hydrophobic yeast transport of these nutrients throughout a 2 h incubation. Hydrophilic cultures of 4918 and ATCC 10231 transported nearly two times more (pmol mg-1 dry weight) proline, mannose, and N-acetyl-D-glucosamine than hydrophobic yeast. Hydrophobic cultures preferentially incorporated serine and aspartic acid in both these strains. Strain variation was indicated with the transport of leucine, lysine, and arginine, as follows: experiments showed that hydrophilic 4918 cultures selectively transported leucine, lysine, and arginine, whereas, the hydrophobic ATCC 10231 cultures incorporated these amino acids.     

Nutritional and metabolic interrelationships of arginine, glutamic acid and proline in the chicken.

Proline satisfies by a narrow margin the criterion for dietary essentially for the chick. It is estimated that the chick may synthesize 80-90% of the total proline needed for growth. Although the metabolism of arginine, ornithine and glutamic acid is expected to give rise to proline, dietary supplements to these amino acids are relatively ineffective in reducing the proline requirement of chicks. Studies of the efficacy of dietary ornithine for growth, and tracer studies using L-(5-3H)arginine indicate that the conversion of ornithine to proline in vivo is limited, and the amount of proline synthesized from arginine is but a small fraction of that needed for growth. The limiting processes in proline synthesis from glutamic acid and ornithine are not known. In Escherichia coli, where the biosynthetic pathway from glutamate to proline has been elucidated, a glutamate kinase, NADP-dependent delta1-pyrroline-5-carboxylic acid (P5C) dehydrogenase and P5C reductase catalyze proline synthesis. P5C reductase is present in the soluble fraction of chicken liver and kidney. An NADP-dependent P5C dehydrogenase activity has also been observed in this fraction of liver. Further studies are required to assess the importance of these enzymes in proline biosynthesis and to determine the limiting process in proline formation in the chicken.     

Changes in free and bound amino acids in experimental silicosis.

The amino acid composition of lung, serum and liver in silicotic rats was studied in order to assess the availability of precursors in lung for fibrogenesis. It was observed that the pool of ornithine, arginine, alanine, leucine, valine, glutamic acid, lysine, proline and glycine underwent marked alterations. Free arginine, proline and leucine were only detectable in silicotic lung, while free glycine, glutamic acid and glutamine pools decreased significantly in liver. Changes in amino acid metabolism as a result of silicosis are discussed.     

Arginine synthesis does not occur during first-pass hepatic metabolism in the neonatal piglet

We have shown that first-pass intestinal metabolism is necessary for approximately 50% of whole body arginine synthesis from its major precursor proline in neonatal piglets. Furthermore, the intestine is not the site of increased arginine synthesis observed during dietary arginine deficiency. Primed constant intravenous (iv) and intraportal (ip) infusions of L-[U-14C]proline, and iv infusion of either L-[guanido-14C]arginine or L-[4,5-3H]arginine were used to measure first-pass hepatic arginine synthesis in piglets enterally fed either deficient (0.20 g.kg(-1).day(-1)) or generous (1.80 g.kg(-1).day(-1)) quantities of arginine for 5 days. Conversion of arginine to other urea cycle intermediates and arginine recycling were also calculated for both dietary treatments. Arginine synthesis (g.kg(-1).day(-1)) from proline was greater in piglets (P < 0.05) fed the deficient arginine diet in both the presence (generous: 0.07; deficient: 0.17; pooled SE = 0.01) and absence (generous: 0.06; deficient: 0.20; pooled SE = 0.01) of first-pass hepatic metabolism. There was no net arginine synthesis from proline during first-pass hepatic metabolism regardless of arginine intake. Arginine conversion to urea, citrulline, and ornithine was significantly greater (P < 0.05) in piglets fed the generous arginine diet. Calculated arginine fluxes were significantly lower (P = 0.01) for [4,5-3H]arginine than for [guanido-14C]arginine, and the discrepancy between the values was greater in piglets fed the deficient arginine diet (35% vs. 20%). Collectively, these findings show that first-pass hepatic metabolism is not a site of net arginine synthesis and that piglets conserve dietary arginine in times of deficiency by decreasing hydrolysis and increasing recycling.     

Arginine catabolism by Treponema denticola.

Treponema denticola, an anaerobe commonly present in the human mouth, ferments various amino acids and glucose. Amino acid analyses indicated that substrate amounts of arginine were utilized by T. denticola growing in a complex, serum-containing medium. Cell suspensions metabolized L-arginine to citrulline, NH3, CO2, proline, and small amounts of ornithine. CO2, NH3, ornithine, and proline were produced from L-citrulline by cell suspensions. Determinations of radioactivity in products formed from L-[U-14C]ornithine indicated that cell suspensions converted this amino acid to proline. Furthermore, proline was excreted by cells growing in a complex, arginine-containing medium. Arginine iminohydrolase (deiminase) and ornithine carbamoyltransferase activities were detected in T. denticola cell extracts. Carbamoylphosphate dissimilation by extracts yielded adenosine triphosphate. The data indicate that T. denticola derives energy by dissimilating L-argine via the arginine iminohydrolase pathway. However, unlike some of the other bacteria that utilize this pathway, T. denticola converts to proline much of the ornithine derived from L-arginine.     

Catabolism of arginine and ornithine in the perfused rat liver: effect of dietary protein and of glucagon

The rates of oxidation of arginine and ornithine that occurred through a reaction pathway involving the enzyme ornithine aminotransferase (EC 2.6.1.13) were determined using (14)C-labeled amino acids in the isolated nonrecirculating perfused rat liver. At physiological concentrations of these amino acids, their catabolism is subject to chronic regulation by the level of protein consumed in the diet. (14)CO(2) production from [U-(14)C]ornithine (0.1 mM) and from [U-(14)C]arginine (0.2 mM) was increased about fourfold in livers from rats fed 60% casein diets for 3-4 days. The catabolism of arginine in the perfused rat liver, but not that of ornithine, is subject to acute regulation by glucagon (10(-7) M), which stimulated arginine catabolism by approximately 40%. Dibutyryl cAMP (0.1 mM) activated arginine catabolism to a similar extent. In retrograde perfusions, glucagon caused a twofold increase in the rate of arginine catabolism, suggesting an effect of glucagon on arginase in the perivenous cells.     

Amino-acid synthesis in adult Dacus oleae (Gmelin) (Diptera Tephritidae) determined with [U-14C] glucose

The ability of adult Dacus oleae for amino-acid synthesis from [U-14C] glucose was investigated. The relatively high specific activity radiometric measurements indicated that both sexes were able to synthesize the amino acids: alanine, aspartic acid, cystine, glutamic acid, glycine, hydroxyproline, proline and tyrosine; therefore, these amino acids are considered as nutritionally dispensable for D. oleae. On the other hand, the amino acids: arginine, histidine, leucine, isoleucine, lysine, methionine, phenylalanine, serine, threonine, and valine, showed a very low specific activity and therefore are considered as nutritionally indispensable. It was not possible to conclude about tryptophane, since the acid hydrolysis destroyed this amino acid.     

Arginine metabolism in insects. Role of arginase in proline formation during silkmoth development

1. Ornithine delta-transaminase (l-ornithine-2-oxo acid aminotransferase, EC 2.6.1.13) and Delta(1)-pyrroline-5-carboxylate reductase [l-proline-NAD(P) 5-oxidoreductase, EC 1.5.1.2] were demonstrated in fat-body and flight-muscle tissues of the silkmoth Hyalophora gloveri. Arginase (l-arginine ureohydrolase, EC 3.5.3.1) is also present in these tissues. 2. Arginase, ornithine transaminase and pyrroline-carboxylate reductase are generally considered to make up the catabolic pathway for the conversion of arginine into proline. The conversion of l-[U-(14)C]arginine into [(14)C]proline by intact fat-body tissue was used to show that the enzymes in insect fat body also function in this capacity. 3. Of the three enzymes of the catabolic pathway, only arginase increased during adult development and the increase coincided with the emergence of the winged adult moth. Since proline appears to be a major substrate utilized in insect flight metabolism, the increase in arginase activity at this stage suggests a major role for arginase in proline formation.     

Utilization of ornithine and arginine as specific precursors of clavulanic acid.

Ornithine and arginine (5 to 20 mM), but not glutamic acid or proline, exerted a concentration-dependent stimulatory effect on the biosynthesis of clavulanic acid in both resting-cell cultures and long-term fermentations of Streptomyces clavuligerus. Ornithine strongly inhibited cephamycin biosynthesis in the same strain. [1-14C]-, [5-14C]-, or [U-14 C] ornithine was efficiently incorporated into clavulanic acid, whereas the incorporation of uniformly labeled glutamic acid was very poor. [U-14C] citrulline were not incorporated at all. Mutant nca-1, a strain that is blocked in clavulanic acid biosynthesis, did not incorporate arginine into clavulanic acid. S. clavuligerus showed arginase activity, converting arginine into ornithine, but not amidinotransferase activity. Both arginase activity and clavulanic acid formation were enhanced simultaneously by supplementing the production medium with 10 mM arginine.     

氯喹对伯氏疟原虫摄取次黄嘌呤、甲硫氨酸、精氨酸及其氨基酸组成的影响

伯氏疟原虫氯喹敏感株和抗氯喹株感染的RBC,与0.4mmol/L氯喹一起培养2小时后,敏感和抗氯喹株感染的RBC,对[~3H]次黄嘌呤、[~(14)C]精氨酸和[~3H]甲硫氨酸的摄入量分别被抑制67.3％、41.8％和35.7％以及65.4％、45.6和46.9％。 感染疟原虫的小鼠,经氯喹10mg/kg肌注20小时后,各氨基酸组成,在敏感株疟原虫中普遍的较不服药的对照组上升,而在抗氯喹疟原虫中,升高的氨基酸主要是与多胺、谷胱甘肽有关,如精氨酸、鸟氨酸、甲硫氨酸、脯鼠酸、甘氨酸和半胱氨酸。