The Valine Catabolic Pathway in Human Liver: Effect of Cirrhosis on Enzyme Activities

Taniguchi, Kenji; Nonami, Toshiaki; Nakao, Akimasa; Harada, Akio; Kurokawa, Tsuyoshi; Sugiyama, Satoru; Fujitsuka, Noriaki; Shimomura, Yoshiharu; Hutson, Susan M.; Harris, Robert A.; Takagi, Hiroshi

doi:10.1002/hep.510240614

Cited by 42 publications

(23 citation statements)

References 29 publications

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“…their intermediate products such as acetyl coenzyme A, α-ketoglutaric acid and fumaric acid participate in the tCA cycle. As reported, branched chain amino acids have been found to be increased in hepatocellular carcinoma due to increased glycolysis (48,49). The present findings may indicate the involvement of glycolysis, and we believe that GC cells selectively utilize amino acids in pathophysiologic metabolism.…”

Section: Discussionsupporting

confidence: 79%

Tissue metabolomic fingerprinting reveals metabolic disorders associated with human gastric cancer morbidity

Wang²,

Liu³

et al. 2011

Oncol Rep

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Abstract. the principal way to improve the outcome of gastric cancer (GC) is to predict carcinogenesis and metastasis at an early stage. the aims of the present study were to test the hypothesis that distinct metabolic profiles are reflected in GC tissues and to further explore potential biomarkers for GC diagnosis. Gas chromatography/mass spectrometry (GC/Ms) was utilized to analyze tissue metabolites from 30 GC patients. A diagnostic model for GC was constructed using orthogonal partial least squares discriminant analysis (OpLs-DA), and the metabolomic data were analyzed using the non-parametric Wilcoxon rank sum test to identify the metabolic tissue biomarkers for GC. Over 100 signals were routinely detected in one single total ion current (tIC) chromatogram, and the OPLS-DA model generated from the metabolic profile of the tissues adequately discriminated the GC tissues from the normal mucosae. Among the low-molecular-weight endogenous metabolites, a total of 41 compounds, such as amino acids, organic acids, carbohydrates, fatty acids and steroids, were detected, and 15 differential metabolites were identified with significant difference (p<0.05). A total of 20 variables were noted which contributed to a great extent in the discriminating OpLs-DA model (VIp value >1.0), among which 12 metabolites were identified using both VIP values (VIP >1) and the Wilcoxon test (p<0.05). In conclusion, the identification of the metabolites associated with GC morbidity potentially revealed perturbations of glycolysis, fatty acid β-oxidation, cholesterol and amino acid metabolism. these results suggest that tissue metabolic profiles have great potential in detecting GC and may aid in understanding its underlying mechanisms.

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Section: Discussionsupporting

confidence: 79%

Tissue metabolomic fingerprinting reveals metabolic disorders associated with human gastric cancer morbidity

Wang²,

Liu³

et al. 2011

Oncol Rep

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“…Notwithstanding the fact that the activity level of hepatic BCKDC is markedly lower in humans than in rats (16,17), BCAA intake-induced upregulation in the liver BCKDC may be involved in the mechanism responsible for the decrease in plasma methionine concentration.…”

Section: Resultsmentioning

confidence: 97%

Effects of Squat Exercise and Branched-Chain Amino Acid Supplementation on Plasma Free Amino Acid Concentrations in Young Women

Shimomura

Kobayashi

Mawatari

et al. 2009

J Nutr Sci Vitaminol

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SummaryThe present study was conducted to examine alterations in plasma free amino acid concentrations induced by squat exercise and branched-chain amino acid (BCAA) supplementation in young, untrained female subjects. In the morning on the exercise session day, participants ingested drinks containing either BCAA (isoleucine : leucine : valine ϭ 1 : 2.3 : 1.2) or dextrin (placebo) at 0.1 g/kg body weight 15 min before a squat exercise session, which consisted of 7 sets of 20 squats, with 3 min intervals between sets. In the placebo trial, plasma BCAA concentrations were decreased subsequent to exercise, whereas they were significantly increased in the BCAA trial until 2 h after exercise. Marked changes in other free amino acids in response to squat exercise and BCAA supplementation were observed. In particular, plasma concentrations of methionine and aromatic amino acids were temporarily decreased in the BCAA trial, being significantly lower than those in the placebo trial. These results suggest that BCAA intake before exercise affects methionine and aromatic amino acid metabolism. Key Words squat exercise, branched-chain amino acids, plasma free amino acids, untrained young women It is well known that amino acid metabolism is affected by exercise ( 1 ). In particular, exercise has been shown to promote branched-chain amino acid (BCAA) catabolism in rats and humans ( 2 , 3 ). Therefore, the popularity of BCAAs as a supplement for people who practice sports is growing. However, despite the common use of BCAAs, little information is available with regard to the effects of BCAA intake on the concentrations of plasma components including free amino acids other than the BCAAs. In a recent study, we have found that BCAA supplementation before squat exercise noticeably suppressed the muscle pain that occurred on the next day after exercise and lasted for a few days (delayed-onset muscle soreness (DOMS)) in young, untrained women ( 4 ). In the present study, we examined alterations in the plasma concentrations of free amino acids induced by squat exercise and BCAA supplementation. Materials and MethodsExperiments were conducted essentially as described previously ( 4 ), except for the following points: (i) 12 young, healthy female volunteers who did not exercise in a regular basis participated in this study, (ii) the subjects ingested the test drink containing BCAA mixture or dextrin at 0.1 g/kg body weight, and (iii) blood samples were collected for preparations of plasma and serum before exercise and at several time points after exercise (see below). The compositions of the test drinks were as follows: a BCAA drink (200 mL) containing 5.5 g of a BCAA mixture (isoleucine, leucine, and valine at a ratio of 1 : 2.3 : 1.2 ( 5 )), 1 g instant green tea powder (Ajinomoto General Foods, Tokyo) and 1.2 g nonnutritive sweetener (Pal Sweet, Ajinomoto, Tokyo), and a placebo drink containing the same ingredients as the BCAA drink except for 5.5 g dextrin instead of the BCAAs ( 4 ). The age of the participants was 22.2 Ϯ 0.5 (mean...

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“…Branched-chain amino acids such as valine, isoleucine, and leucine are mainly catabolized in muscle cells in humans (16,17). Thus, the urinary excretion amounts of branched-chain 2-oxo acids such as 2-oxo-3-methylbutanoic acid, 2-oxo-3-methylpentanoic acid, and 2-oxo-4-methylpentanoic acid reflect the catabolic activity of branched-chain amino acids in muscle cells.…”

Section: Discussionmentioning

confidence: 99%

Urinary Branched-Chain 2-Oxo Acids as a Biomarker for Function of B-Group Vitamins in Humans

Shibata

Sakamoto

2016

J Nutr Sci Vitaminol

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SummaryTo find a functional biomarker of B-group vitamins, we collected 24-h urine samples from young Japanese women who lived in the community (n529) to measure branched-chain 2-oxo acids such as 2-oxo-3-methylbutanoic acid, 2-oxo-3-methylpentanoic acid, and 2-oxo-4-methylpentanoic acid because B-group vitamins are involved in the catabolism of branched-chain amino acids. The relationships between each pair of the three urinary 2-oxo acids were very high (2-oxo-3-methylbutanoic acid and 2-oxo-3-methylpentanoic acid, p,0.001; 2-oxo-3-methylbutanoic acid and 2-oxo-4-methylpentanoic acid, p,0.001; 2-oxo-3-methylpentanoic acid and 2-oxo-4-methylpentanoic acid, p,0.001). The participants were divided into three groups using the upper (n510), middle (n59), and lower tertiles (n510) based on the urinary excretion amounts of the sum of the three branchedchain 2-oxo acids. The administration of capsules containing the daily necessary amounts of B-group vitamins led to a decrease in the urinary excretion of the sum of the three types of branched-chain 2-oxo acids in participants belonging to the upper tertile. A similar phenomenon was observed in the middle tertile, but not in the lower tertile. Intakes of B-group vitamins and the urinary excretion amounts of B-group vitamins were not observed to be significantly different among the upper, middle, and lower tertiles. These results indicate that some young Japanese women need much higher levels of B-group vitamins than the Dietary Reference Intakes for Japanese. Thus, urinary branched-chain 2-oxo acids are useful functional biomarkers for B-group vitamins in humans.

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The Valine Catabolic Pathway in Human Liver: Effect of Cirrhosis on Enzyme Activities

Cited by 42 publications

References 29 publications

Tissue metabolomic fingerprinting reveals metabolic disorders associated with human gastric cancer morbidity

Tissue metabolomic fingerprinting reveals metabolic disorders associated with human gastric cancer morbidity

Effects of Squat Exercise and Branched-Chain Amino Acid Supplementation on Plasma Free Amino Acid Concentrations in Young Women

Urinary Branched-Chain 2-Oxo Acids as a Biomarker for Function of B-Group Vitamins in Humans

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