Ornithine Carbamyl Transferase Research Articles

Zinc Imidazole Framework‐8 Nanoparticles Disperse MRSA Biofilm by Inhibiting Arginine Biosynthesis and Down‐Regulating Adhesion‐Related Proteins

AbstractNanomaterials, including ZIF‐8 nanoparticles (NPs), are shown to be effective antimicrobial agents against Methicillin‐resistant Staphylococcus aureus(MRSA). However, the antibiofilm properties and mechanisms of ZIF‐8 NPs remain uncertain. In this study, ZIF‐8 NPs are prepared using the room temperature solution reaction method and characterized. Biofilm formation inhibition test and biofilm eradication test are performed and the results show that ZIF‐8 NPs can inhibit the formation of MRSA biofilm as well as disperse established MRSA biofilm. Proteomics and real‐time fluorescence quantitative polymerase chain reaction (PCR) are conducted to prove that ZIF‐8 NPs reduce the expression of adhesion‐related proteins, namely the fibronectin‐binding proteins A and B (fnbA/fnbB), fibrinogen binding protein caking factors A and B (clfA/clfB), elastin binding protein (ebps), and fibrin binding protein (eno). ZIF‐8 NPs also inhibit the arginine biosynthesis pathway by affecting the activities of argininosuccinate lyase, ornithine carbamyl transferase, Glutamate dehydrogenase, carbamate kinase, and arginine deiminase. A conclusion can be drawn from the above results that ZIF‐8 NPs can inhibit bacterial adhesion and kill bacteria directly, ultimately destroying MRSA biofilm. This study provides a molecular basis for the treatment of MRSA biofilm with ZIF‐8 NPs.

Hepatocellular neoplasms arising in genetic metabolic disorders: steatosis is common in both the tumor and background liver

Hepatocellular neoplasms can develop in multiple genetic metabolic disorders. While there have been rare case reports, clinical and pathological characterizations have not been systematically performed. We conducted a retrospective study in 9 patients with these rare genetic metabolic disorders, including glycogen storage disease type 1, ornithine carbamyl transferase deficiency, hereditary tyrosinemia type 1, and Navajo neurohepatopathy, who developed hepatocellular neoplasms. Our results show that steatosis is a common finding in both tumor (6/9 cases, 67%) and background liver parenchyma (8/9 cases, 89%), underlying a possible role for steatosis in tumorigenesis in these genetic metabolic disorders. Our findings also raise a consideration of underlying genetic metabolic disorder when young patients with hepatocellular neoplasm show steatosis in both the tumor and background liver.

Ammonia and coma \u2013 a case report of late onset hemizygous ornithine carbamyltransferase deficiency in 68-year-old female

BackgroundAcute hyperammonemia without signs of common causes in the elderly might be challenging to identify. We report the oldest case known to date of a female patient with late onset ornithine carbamyltransferase deficiency (OTC), which was unmasked after a protein overload due to nutritional supplements. Our case illustrates how environmental factors (protein overload) in previously unknown OTC in the elderly leads to hyperammonemic encephalopathy and highlights that early treatment prevents persisting neurological deficits and should be considered in absence of common causes of hyperammonemic encephalopathy.Case presentationA 68-year-old woman presented with acute confusion, which progressed into a deep coma (Glasgow-Coma-Scale score 3) within a few hours.The only remarkable finding was a plasma ammonia (NH3) concentration of 697 μmmol/l (range 12–47 μmmol/). Third party history revealed that the patient disliked meat for most of her life (meat = protein, which needs to be metabolized) and had taken nutritional supplements (since supplements often have a high protein-ratio) 2 days before the symptoms started. Protein catabolism results in NH3, which is metabolized via the urea cycle. Consequently, the acute hyperammonemia in our patient was thought to be related to an inherited metabolic disorder, which only unmasked itself as a result of an overload of the corresponding metabolite (in this case protein). Since ornithine carbamyltransferase deficiency (OTC) is the most common inherited urea cycle disorder, this diagnosis became likely and was confirmed later via genetic and metabolic testing (amino acids, orotic acid, etc.). After 2 weeks of treatment (dialysis, low-protein-diet, nitrogen-lowering medication) the patient was discharged in a healthy condition without any neurological deficits.ConclusionOTC is a x-chromosomal linked disorder, that usually manifests in newborn infants and children, but also rarely in adults and even rarer in the elderly (50- till 60-years-old), where it is probably underdiagnosed. In case of hyperammonemic encephalopathy – regardless of the underlying cause -, treatment should be started early to prevent persisting neurological deficits. OTC should be considered in absence of common causes of hyperammonemic encephalopathy.

A healthy neonate born at the third pregnancy of a woman with ornithine carbamoyltransferase deficiency under multidisciplinary management

We reported a women with ornithine carbamoyltransferase deficiency who delivered a healthy boy after two pregnancies with adverse outcome with the help of a multidiscipline team. The woman was admitted to Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine with an acute prenatal hyperammonemic episode at 28 gestational weeks of her first pregnancy in 2013 and was diagnosed with ornithine transcarbamylase deficiency. Her hyperammonemic complications were controlled under a well-planned multidisciplinary management including a low-protein diet and appropriate medications assisting nitrogen removal. A boy was delivered by cesarean section at 32 weeks of gestation but died three days later. Mutation analysis revealed a hemizygous c.583G>A (G195R) mutation in the neonatal ornithine carbamyltransferase gene and his mother was a heterozygous carrier with the same mutation. Two years later in 2015, the patient was pregnant spontaneously. However, she received an induced abortion at 21 weeks of gestation because amniocentesis and DNA analysis showed that the male fetus had the same ornithine transcarbamylase gene mutation. The index pregnancy was assisted by in vitro fertilization-embryo transfer and preimplantation genetic diagnosis in 2017 and the woman delivered a healthy boy with the management of a multidisciplinary team. Key words: Ornithine carbamoyltransferase deficiency disease; Gravidity; Peripartum period; Patient care management

METABOLIC DISEASE : DEFICIT IN ORNITHINE CARBAMYL TRANSFERASE ABOUT AN OBSERVATIONAL CASE

Introduction The deficiency in ornithine carbamyl transferase (OCT) is an enzyme deficiency transmitted in the recessive or dominant mode associated with X. Complete deficit is still expressed in hemizygous boys in a very severe and often fatal neonatal hyperammonic coma. We report a clinical case of a revelation of an OCT enzyme deficiency in a newborn. Observation This is a female newborn, a premature mother and a scheduled caesarean delivery. At J7 of life, neonatal hypotonia appeared, stable on the liver and respiratory level. The anterior fontanelle is normotendue, with a malformative balance without peculiarities. The lumbar puncture performed is normal. The biochemical assessment carried out showed low uremia, hypocalcemia and very high hyperammoniemia. Viral and bacterial serologies were negative. The hemogram performed was normal, the hemostasis balance showed a low TP with an elongated TCA and decreased fibrinogen. Factor V was collapsed with a value of 21%. The patient was hospitalized in neonatal resuscitation. The chromatography of the amino acids was able to confirm a metabolic disease whose diagnosis is an OCT deficiency. Conclusion The expression of hereditary metabolic diseases in the neonatal period is not very specific. Metabolic exploration should be systematically in the face of any situation of neonatal distress.

What is the role of intestinal citrulline production in protein homeostasis?

Rationale: Plasma citrulline (Cit) is mainly determined by the balance between its production by the gut and its renal conversion to arginine (Arg). Enterocytes, like hepatocytes, express ornithine carbamyl transferase (OCT), that converts ornithine (Orn) to Cit. As our studies demonstrate that pharmacological doses of Cit activate muscle protein synthesis, we questioned whether intestinal OCT may be a major effector of muscle homeostasis. Since neonatal OCT deficiency is associated with early lethality, this was addressed in a model of conditional intestinal OCT invalidation enabling to specifically suppress OCT intestinal expression in adult mice.

Dietary arginine supplementation does not improve nutrient utilisation in gilthead seabream

The aim of this study was to evaluate the beneficial effects of dietary arginine supplementation on growth performance, urea biosynthesis, and N excretion of juvenile gilthead sea bream (Sparus aurata) fed fish meal and plant-feedstuffs based diets. For that purpose, five isonitrogenous (45% crude protein) diets were formulated as follows: two diets were fish meal-based and contained 3.0 and 4.0% arginine; three diets were plant feedstuff-based and contained 1.6, 3.0, and 4.0% arginine. Triplicate groups of gilthead seabream juveniles (24g) were fed each diet for 10weeks. At the end of the trial, growth performance of fish fed the fish meal-based diets was higher than that of the other groups. Dietary arginine content did not affect growth performance.Ammonia excretion was not affected by diet composition, while urea excretion was directly related with arginine intake. Carbamyl phosphate synthase activity was not detected in the liver, while arginase activity increased and ornithine carbamyl-transferase decreased with dietary arginine content.Overall, an excess of dietary arginine had no beneficial effects on growth performance and feed utilisation of gilthead seabream juveniles fed plant feedstuffs-based diets. A functional urea cycle was not detected in the liver of gilthead sea bream juveniles.

Survival of Primary Human Hepatocytes and Death of Induced Pluripotent Stem Cells in Media Lacking Glucose and Arginine

BackgroundTumorigenicity is an associated risk for transplantation of hepatocytes differentiated from human induced pluripotent stem (hiPS) cells. Hepatocytes express the enzymes galactokinase and ornithine transcarbamylase (OTC) to aid in their own survival. However, hiPS cells do not express these enzymes, and therefore, are not be expected to survive in a medium containing galactose and ornithine and lacking glucose and arginine.Materials and MethodsReal-time quantitative polymerase chain reaction (PCR) was performed to analyze the expression of galactokinase 1 (GALK1)1 and GALK2, ornithine carbamyltransferase, and phenylalanine hydroxylase (PAH). The hiPS cell line 201B7 was cultured in hepatocyte selection medium (HSM), which lacks glucose and arginine but contains galactose and ornithine. Furthermore, microscopic analysis of the cultured cells was performed after hematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). The hiPS cells were immunostained to assess their pluripotency in HSM. In addition, the primary human hepatocytes were cultured with or without hiPS cells in HSM.ResultsThe expression levels of GALK1, GALK2, OTC, and PAH in 201B7 were 22.2±5.0 (average ± standard deviation), 14.2% ±1.1%, 1.2% ±0.2%, and 8.4% ±0.7% respectively, compared with those in the adult liver. The hiPS cell population diminished when cultured in HSM and completely disappeared after 3 days. The cultured cells showed condensation or fragmentation of their nuclei, thereby suggesting apoptosis. TUNEL staining confirmed that the cells had undergone apoptosis. The 201B7 cells were positive for Nanog, SSEA-4, and TRA-1-60. The primary human hepatocytes survived when cultured alone in HSM and when co-cultured with hiPS cells.ConclusionTherefore, HSM is and ideal medium for eliminating hiPS cells and purifying hepatocytes without inducing any damage.

Hydrogenosome-localization of arginine deiminase in Trichomonas vaginalis

The arginine dihydrolase (ADH) pathway has an analogous function to the urea cycle in mitochondria-containing cells, by removing nitrogen from amino acids and generating ATP. Subcellular localization of the ADH pathway enzymes in Trichomonas vaginalis revealed that arginine deiminase (ADI) localizes to the hydrogenosome, a mitochondrion-like organelle of anaerobic protists. However the other enzymes of the ADH pathway, ornithine carbamyltransferase and carbamate kinase localize to the cytosol. Three gene sequences of T. vaginalis ADI (ADI 1–3) were identified in the T. vaginalis genome, all having putative mitochondrial targeting sequences. The ADI sequences were cloned and used to probe T. vaginalis using a carboxyterminal di-hemogglutinin epitope tag which demonstrated co-localization with malic enzyme confirming the hydrogenosome localization of this enzyme.

Serum ornithine carbamyltransferase reflects hepatic damage in diabetic obese mice

As ornithine carbamyltransferase (OCT) has proved to be a sensitive serum marker in the detection of hepatotoxicity in several models, it is important to confirm its application to the diagnosis of non-alcoholic fatty liver disease. C57BL/6, KK-Ta and KK-Ay mice were fed a high-fat diet for 8 weeks and serum enzyme markers were examined. Serum OCT and alanine aminotransferase (ALT) were also measured in diabetic obese ob/ob and db/db mice fed a normal diet. Liver damage in these mice was evaluated by the hepatic content of tumor necrosis factor-alpha. Serum levels of OCT increased in KK-Ay fed a high-fat diet compared with the normal diet-fed group, whereas C57BL/6 and KK-Ta mice were not affected. In ob/ob mice, the relative increase was always greater in OCT than in ALT. In contrast, in db/db mice, the relative increase was always greater in ALT. Hepatic tumor necrosis factor-alpha was significantly elevated in ob/ob mice, but not in db/db mice. Serum OCT seemed to reflect tumor necrosis factor-alpha-mediated hepatic damage when compared with ALT in diabetic obese mice and could be useful in the application for non-alcoholic fatty liver disease with features of metabolic syndrome, such as obesity and diabetes.

Marked elevation of serum mitochondrion‐derived markers in mild models of non‐alcoholic steatohepatitis in rats

In order to find sensitive serum markers in non-alcoholic steatohepatitis, liver-specific injury markers were thoroughly examined in mild models of NASH in rats. Wistar and Sprague-Dawley rats were fed a choline-deficient diet for 4 weeks, and serum activities of liver-specific enzyme markers were examined. In the drug-induced steatohepatitis model, tetracycline (0.4 mmol/kg) was given i.p. to rats and the course of hepatotoxicity was evaluated with serum markers, together with the accumulation of total lipid and thiobarbituric acid-reactive substances in the liver. In Wistar rats, serum activities of most enzymes tested were significantly increased. In Sprague-Dawley rats, in contrast, the serum level of ornithine carbamyltransferase and glutamate dehydrogenase were markedly elevated in the choline-deficient diet group compared with the control diet groups, whereas other markers were not significantly increased. In the tetracycline-induced steatohepatitis model, the extent of the increase was much higher in mitochondrial markers and the peak of the increase in these markers corresponded with the increase of hepatic total lipid and thiobarbituric acid-reactive substance. These observations show that serum mitochondrial enzyme markers are potent markers for non-alcoholic steatohepatitis in rats and are possibly applicable to humans.

Ornithine carbamyltransferase is a sensitive marker for alcohol-induced liver injury

Background Although mitochondrion-derived markers such as ornithine carbamyltransferase (OCT) and glutamate dehydrogenase (GLDH) have been reported to be good markers for alcohol-induced hepatic injury, their use has been limited due to the notion that mitochondrial markers are less sensitive than cytosol-derived markers. We determined the clinical importance of mitochondrion-derived markers in the evaluation of alcohol-induced hepatotoxicity. Methods Rats were administered alcohol chronically (5–30% ethanol in drinking water with or without high fat diet feeding for 15 weeks) and hepatic damages were evaluated by serum OCT and GLDH, together with other liver enzymes such as alanine aminotransferase and aspartate aminotransferase. Hepatic content of the enzymes was also evaluated in the chronic ethanol feeding model to confirm whether induction of the enzyme in the liver reflects the serum activity. Results The serum activities of OCT and GLDH increased significantly by chronic ethanol feeding while other markers did not. Although the hepatic content of OCT and GLDH also increased, the serum activities did not correlate with the hepatic activities and the extent of increase in the liver was much less than in serum. Conclusions Mitochondrion-derived markers, especially OCT, appeared superior to cytosol-derived markers in the detection of alcohol-induced liver injury.

Superiority of serum type-I arginase and ornithine carbamyltransferase in the detection of toxicant-induced acute hepatic injury in rats

BackgroundDespite the restricted distribution to mitochondria of hepatocytes in the periportal region, ornithine carbamyltransferase (OCT) have been suggested to be a sensitive marker in addition to type-I arginase (ARG), even in centrilobular damage of the liver. We attempted to confirm the universal advantages of ARG and OCT in the evaluation of hepatotoxicity induced by toxicants, and to clarify whether the character of a marker is a more important factor than its localization in its clinical superiority. MethodsRats were administered carbon tetrachloride, allyl alcohol, d-galactosamine, lipopolysaccharide, and concanavalin A and the course of damage was monitored by serum ARG and OCT, together with alanine aminotransferase (ALT) and aspartate aminotransferase (AST). ResultsThe significant increase in the serum levels of the markers was faster in ARG and OCT than AST and ALT. Further, the extent of the increase at the peak was always higher in ARG and OCT than in AST and ALT. ConclusionThe superiority of ARG and OCT over AST and ALT in the detection of hepatotoxicity seems universal, at least in toxicant-induced acute liver injuries. The apparent faster appearance of mitochondria-derived enzyme, OCT, in serum than cytosol-derived enzyme, ALT, shows that leakage into the circulation is dependent on the marker rather than its localization.

Mitofusin 2 Protects Cerebellar Granule Neurons against Injury-induced Cell Death

Of the GTPases involved in the regulation of the fusion machinery, mitofusin 2 (Mfn2) plays an important role in the nervous system as point mutations of this isoform are associated with Charcot Marie Tooth neuropathy. Here, we investigate whether Mfn2 plays a role in the regulation of neuronal injury. We first examine mitochondrial dynamics following different modes of injury in cerebellar granule neurons. We demonstrate that neurons exposed to DNA damage or oxidative stress exhibit extensive mitochondrial fission, an early event preceding neuronal loss. The extent of mitochondrial fragmentation and remodeling is variable and depends on the mode and the severity of the death stimuli. Interestingly, whereas mitofusin 2 loss of function significantly induces cell death in the absence of any cell death stimuli, expression of mitofusin 2 prevents cell death following DNA damage, oxidative stress, and K+ deprivation induced apoptosis. More importantly, whereas wild-type Mfn2 and the hydrolysis-deficient mutant of Mfn2 (Mfn2(RasG12V)) function equally to promote fusion and lengthening of mitochondria, the activated Mfn2(RasG12V) mutant shows a significant increase in the protection of neurons against cell death and release of proapoptotic factor cytochrome c. These findings highlight a signaling role for Mfn2 in the regulation of apoptosis that extends beyond its role in mitochondrial fusion.

Carbamyl Phosphate Biosynthesis: the Work of Mary Ellen Jones

Carbamyl Phosphate Biosynthesis: the Work of Mary Ellen Jones

Control of nitrogen homeostasis: intestinal arginine metabolism regulation according to protein supply.

Portal arginine (Arg) flow plays a key role in liver ureagenesis. In the intestine, Arg can be converted into citrulline (Cit) via arginase and ornithine carbamyl-transferase (OCT). Cit can also be synthesized from glutamine via glutaminase and ornithine aminotransferase (OAT). The aim of this work was to study the regulation of these enzymes in the intestine in relation to time and level of protein supply. 48 rats were divided in 6 groups to receive a 10% (10P), 17% (17P) or 25% protein (25P) diet for either 16 hours short-term (ST) or 15 days long-term (LT). LT group urines were collected to determine N balance. At sacrifice, blood was collected for plasma amino acid measurement, and the intestinal mucosa was removed for enzyme expression and activity analysis (results are given as means ± SEM, ANOVA + Newman-Keuls test [∗ vs. 17P: p < 0.05]). N balance remained similar in all groups. Cit plasma levels at LT varied with diet (10P: 87 ± 2 ∗; 17P: 69 ± 4; 25P: 88 ± 5 ∗ in mM). There was an increase in ileum at ST in arginase activity under 25P and 10P diets (respectively 46 ± 2 and 46 ± 2 vs. 36 ± 3 (17P) in μmol/g/min) and at LT, in OAT expression in the 10P group (+ 277 %∗). With an hypoproteic diet, Cit synthesis appears to be ensured by either OAT activation at LT or arginase at ST. Surprisingly, both low and high protein diets increased Cit production. Research is needed to gain further insight into the regulation of this complex metabolic network.

Characterization of the arginine deiminase ofStreptococcus equisubsp.zooepidemicus

Streptococcus equi subsp. zooepidemicus is an important cause of infectious diseases in horses and rarely humans. Little is known about the virulence factors or protective antigens of S. equi subsp. zooepidemicus. In the present study, I designed original primers based on an alignment of the gene sagp(arcA) from Streptococcus pyogenes encoding streptococcal acid glycoprotein-arginine deiminase (SAGP/AD) to amplify the S. equi subsp. zooepidemicus counterpart sequence by polymerase chain reaction, and I analyzed the sagp(arcA) gene of the organism. Using chromosomal walking steps, I identified a contiguous eight-gene locus involved in SAGP/AD production. Their open reading frames were found to share significant homologies and to correspond closely in molecular mass to previously sequenced arc genes of S. pyogenes, thus they were designated ahrC.2 (arginine repressor), arcR (CRP/FNR transcription regulator), sagp(arcA) (streptococcal acid glycoprotein-arginine deiminase), putative acetyltransferase gene, arcB (ornithine carbamyl transferase), arcD (arginine-ornithine antiporter), arcT (Xaa-His peptidase), and arcC (carbamate kinase). The SAGP homologue of S. equi subsp. zooepidemicus (SzSAGP), encoded by arcA gene of the bacteria (arcA(SZ)), was successfully expressed in Escherichia coli and purified to homogeneity. When in vitro growth inhibitory activity of the recombinant SzSAGP was tested against MOLT-3 cells, it inhibited the growth of the cells during the 3 days of culture in a dose-dependent manner, accompanied by the induction of apoptotic cell death. The recombinant protein also possessed AD activity. By immunoblot analysis using both anti-SzSAGP-SfbI(H8) and anti-SfbI(H8) sera, I was able to demonstrate that the SzSAGP protein is expressed on the streptococcal surface.

Reverse effects of zoledronic acid on the malignant phenotype of Bel-7402 human hepatocancinoma cells

目的 探讨唑来膦酸诱导Bel-7402人肝癌细胞分化作用,为肝癌的分化治疗提供可借鉴的资料.方法选用反映肝细胞恶变的甲胎蛋白(AFP)的分泌量、γ-谷氨酰转肽酶(γ-GT)和醛缩酶(ALD),反映肝癌细胞分化的酶学指标酪氨酸-α-酮戊二酸转氨酶(TAT),鸟氨酸氨基甲酰转移酶(OCT)和碱性磷酸酶(ALP)作为观察肝癌细胞恶性表型逆转的指标.结果Bel-7402人肝癌细胞经0.05ug/ml唑来膦酸处理后,AFP分泌量明显低于对照组,γ-GT和ALD活力也明显低于对照组;相反,OCT、TAT和ALP的活力则明显高于对照组,差异均有显著意义(P＜0.05或P＜0.01).结论证明唑来膦酸是体外培养Bel-7402人肝癌细胞有效的分化诱导剂。

The effect of nucleic acids on growth, ureagenesis and nitrogen excretion of gilthead sea bream Sparus aurata juveniles

The aim of this trial was to evaluate the effect of dietary nucleic acids on ureagenesis and nitrogen balance in gilthead sea bream juveniles. For that purpose, 5 isonitrogenous (7.25% N) diets were formulated based on fish meal as protein source (FM-control diet) and to partially replace the fish meal nitrogen with two levels of nucleic acids (diets RNA1 and RNA2) or brewers yeast (diets BY1 and BY2). Each diet was fed for 10 weeks, to apparent visual satiety, to triplicate groups of 50 fish each with an average body weight of 12.7 g. Inclusion of nucleic acid N either as brewers yeast or RNA led to significant improvement of feed intake and growth, except for fish fed diet RNA2. There were no differences in final weight between groups fed the yeast- and the RNA-containing diets. Although there was an improvement of growth rate of fish fed the RNA or yeast containing diets, dietary nucleic acid supplementation did not have a clear N sparing effect. At the end of the trial there were no significant differences in whole body composition among groups, except for the lipid content which was significantly higher in fish fed the Y2 diet. Hepatic glutamate dehydrogenase activity levels did not differ among groups. Ornithine carbamyl transferase activities were very low in all groups, but appear to be induced by high levels of dietary RNA. Fish fed the yeast diets exhibited the highest arginase activity of all groups. No increase of uricase activities was observed in fish fed the RNA supplemented diets. Ammonia and urea excretion of fish fed the RNA-including diets was higher or significantly higher than in the other groups. Plasma urea levels were higher in fish fed the RNA diets than in the other groups confirming excretion data in that dietary nucleic acid influenced urea excretion through uricolysis. In conclusion, substitution of N supplied by fish meal by that supplied by brewers yeast had a positive effect on growth performance of sea bream, while dietary nucleic acid supplementation did not have a clear N sparing effect. At a dietary level of 11.5% of RNA extract, there was no improvement of fish performance compared to the control, possibly due to an insufficient capacity of fish to degrade high levels of nucleic acid. Data on excretion and plasma metabolites strongly suggest that purinolysis contributes also to ureogenesis in gilthead sea bream.

Beneficial effects of branched-chain amino acids on altered protein and amino acid metabolism in liver cirrhosis: evaluation in a model of liver cirrhosis induced in rats with carbon tetrachloride

The effect of branched-chain amino acids (BCAA) on the metabolism of protein, amino acids and ammonia was examined in rats with cirrhosis, with a special emphasis on the efficacy of early administration of BCAA. Liver cirrhosis was induced in rats by intraperitoneal injections of carbon tetrachloride (CCl 4). The rats were divided into three groups: early-, late- and untreated. The early- and late-treated groups were given BCAA rich food from the early and late stage of liver cirrhosis, while the untreated group was given standard food throughout. Concentrations of amino acids and ammonia in the plasma and the ornithine carbamyl transferase (OCT) activity in the liver were evaluated, and compared with control group after 15 weeks maintenance. Ammonia was significantly higher in the late- and untreated groups, but not in the early-treated group. BCAA, tyrosine, and methionine were significantly lower in the untreated and late-treated groups. Glutamine increased significantly in the un-, late- and early-treated groups. However, no significant differences were found among three groups. A significant difference was found in 3-methyl histidine (3-MH) between the early- and late-treated groups. This study suggests that the administration of BCAA from early stage of liver cirrhosis inhibits breakdown of protein and improves metabolism of protein, amino acids and ammonia.