• Asian-Australasian Journal of Animal Sciences
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• v.28 no.12
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• pp.1742-1750
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• 2015

As a novel approach for disease control and prevention, nutritional modulation of the intestinal health has been proved. However, It is still unknown whether branched-chain amino acid (BCAA) is needed to maintain intestinal immune-related function. The objective of this study was to determine whether BCAA supplementation in protein restricted diet affects growth performance, intestinal barrier function and modulates post-weaning gut disorders. One hundred and eight weaned piglets ($7.96{\pm}0.26kg$) were randomly fed one of the three diets including a control diet (21% crude protein [CP], CON), a protein restricted diet (17% CP, PR) and a BCAA diet (BCAA supplementation in the PR diet) for 14 d. The growth performance, plasma amino acid concentrations, small intestinal morphology and intestinal immunoglobulins were tested. First, average daily gain (ADG) (p<0.05) and average daily feed intake (ADFI) (p<0.05) of weaned pigs in PR group were lower, while gain:feed ratio was lower than the CON group (p<0.05). Compared with PR group, BCAA group improved ADG (p<0.05), ADFI (p<0.05) and feed:gain ratio (p<0.05) of piglets. The growth performance data between CON and BCAA groups was not different (p>0.05). The PR and BCAA treatments had a higher (p<0.05) plasma concentration of methionine and threonine than the CON treatment. The level of some essential and functional amino acids (such as arginine, phenylalanine, histidine, glutamine etc.) in plasma of the PR group was lower (p<0.05) than that of the CON group. Compared with CON group, BCAA supplementation significantly increased BCAA concentrations (p<0.01) and decreased urea concentration (p<0.01) in pig plasma indicating that the efficiency of dietary nitrogen utilization was increased. Compared with CON group, the small intestine of piglets fed PR diet showed villous atrophy, increasing of intra-epithelial lymphocytes (IELs) number (p<0.05) and declining of the immunoglobulin concentration, including jejunal immunoglobulin A (IgA) (p = 0.04), secreted IgA (sIgA) (p = 0.03) and immunoglobulin M (p = 0.08), and ileal IgA (p = 0.01) and immunoglobulin G (p = 0.08). The BCAA supplementation increased villous height in the duodenum (p<0.01), reversed the trend of an increasing IELs number. Notably, BCAA supplementation increased levels of jejunal and ileal immunoglobulin mentioned above. In conclusion, BCAA supplementation to protein restricted diet improved intestinal immune defense function by protecting villous morphology and by increasing levels of intestinal immunoglobulins in weaned piglets. Our finding has the important implication that BCAA may be used to reduce the negative effects of a protein restricted diet on growth performance and intestinal immunity in weaned piglets.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.2 no.1
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• pp.85-88
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• 2002

Methylmalonic acidemia is an inborn error of branched chain amino acid metabolism, clinically characterized by lethargy, vomiting, and hypertonia with abnormal movements, and biochemically characterized by ketoacidosis, hyperammonemia, and sometimes hyperglycinemia. Conventional treatment of methylmalonic acidemia incluides dietary protein restriction, bicarbonate, carnitine, and metronidazole. However, most patient have recurrent episodes of acidosis, and a significant number have neurologic deficits and renal impairment. We report the successful treatment of a patient with methylmalonic acidemia by liver transplantation.

• Bulletin of the Korean Chemical Society
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• v.28 no.6
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• pp.947-952
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• 2007

Mycobacterium tuberculosis is a pathogen responsible for 2-3 million deaths every year worldwide. The emergence of drug-resistant and multidrug-resistant tuberculosis has increased the need to identify new antituberculosis targets. Acetohydroxy acid synthase, (AHAS, EC 2.2.1.6), an enzyme involved in branched-chain amino acid synthesis, has recently been identified as a potential anti-tuberculosis target. To assist in the search for new inhibitors and “receptor-based” design of effective inhibitors of tubercular AHAS (TbAHAS), we constructed four different structural models of TbAHAS and used one of the models as a target for virtual screening of potential inhibitors. The quality of each model was assessed stereochemically by PROCHECK and found to be reliable. Up to 89% of the amino acid residues in the structural models were located in the most favored regions of the Ramachandran plot, which indicates that the conformation of each residue in the models is good. In the models, residues at the herbicide-binding site were highly conserved across 39 AHAS sequences. The binding mode of TbAHAS with a sulfonylurea herbicide was characterized by 32 hydrophobic interactions, the majority of which were contributed by residue Trp516. The model based on the highest resolution X-ray structure of yeast AHAS was used as the target for virtual screening of a chemical database containing 8300 molecules with a heterocyclic ring. We developed a short list of molecules that were predicted to bind with high scores to TbAHAS in a conformation similar to that of sulfonylurea derivatives. Five sulfonylurea herbicides that were calculated to efficiently bind TbAHAS were experimentally verified and found to inhibit enzyme activity at micromolar concentrations. The data suggest that this time-saving and costeffective computational approach can be used to discover new TbAHAS inhibitors. The list of chemicals studied in this work is supplied to facilitate independent experimental verification of the computational approach.

• Bulletin of the Korean Chemical Society
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• v.26 no.6
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• pp.916-920
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• 2005

Acetohydroxy acid synthase catalyzes the first common step in the biosynthesis of branched chain amino acids. AHAS plays two distinct metabolic roles, and is designated as anabolic AHAS and catabolic AHAS, depending on its function. Anabolic AHAS is FAD-dependent, while its catabolic counterpart is not. In this work, a conserved motif was identified in the $\beta$-domain of anabolic AHASs, but not in catabolic AHAS ($_{372}RFDDR_{376}$). In order to determine the functions of this motif, we replaced the motif with the corresponding sequence in FAD-independent AHAS, SPVEY. None of these three mutants (SPV, SPVE, and SPVEY) was detected with bound FAD. However, two of these mutants (SPVE and SPVEY) were active at a low level of specific activity. Although they exhibited pyruvate- and ThDP- dependent characteristics, the activity of the two active mutants appears to be FAD-independent. The SPVEY mutant was completely insensitive to the three tested herbicides, even at extremely high concentrations and is also somewhat more thermolabile than the wild type enzyme. The data provided in this work suggest that the RFDDR motif is a possible determinant of the FAD-dependent and herbicide-resistant properties of tobacco AHAS. The SPVEY mutant appears to exhibit catabolic AHAS-like activity.

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.4
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• pp.479-484
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• 2001

The effect of dietary supplementation of sodium salt of isobutyric acid in low protein (10% CP) wheat straw based diet on nutrient utilization and rumen fermentation was studied in ruminally fistulated male crossbred cattle. The study included a 7 day metabolism and a 3 day rumen fermentation trials. The cattle were distributed into two equal groups of 4 each. The animals of control group were fed a basal diet consisting of wheat straw, concentrate mixture and green maize fodder in 40:40:20 proportion whereas branched chain volatile fatty acid (BCFA) supplemented group received a basal diet + isobutyric acid at 0.75 percent of basal diet. The duration of study was 36 days. The feed intake between experimental groups did not differ significantly and the average total DMI (% BW) was 2.01 and $2.28kg\;day^{-1}$ in control and BCFA supplemented diets. The dietary supplementation of BCFA improved (p<0.05) the DM, OM, NDF and cellulose digestibility by 4.46, 6.63, 10.57 and 11.31 per cent over those fed control diet. The total N retention on BCFA supplementation was improved (p<0.01) due to decreased (p<0.05) urinary N excretion. The concentrations of ruminal total N was 37.07 and $34.77mg\;100ml^{-1}$ in control and BCFA fed groups, respectively. Dietary supplementation BCFA significantly (p<0.01) reduced the ruminal ammonia N concentration as compared to control and the mean values ($mg\;100ml^{-1}$) were 13.18 and 9.42 in control and BCFA fed groups. The total VFA concentration was higher (p<0.01) in BCFA supplemented group (101.14 mM) than the control (93.05 mM). Among the VFAs, the molar proportion of acetate was higher (p<0.01) in BCFA supplemented group (71.07 mM) as compared to control (64.98 mM). However, the concentration of propionate and butyrate remained unchanged. Amino acids composition of bacterial hydrolysates was similar in both the groups. Ruminal outflow rate of liquid digesta was higher (p<0.01) in BCFA fed group ($67.56l\;day^{-1}$) than control ($52.73l\;day^{-1}$). It is concluded that the dietary supplementation of Na-salt of isobutyric acid in low protein diet improved the nutrient utilization and ruminal fermentation characteristics.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.2
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• pp.31-38
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• 2023

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder caused by a deficiency in branched chain α-keto acid dehydrogenase (BCKAD). Between 1997, when Korea's MSUD case was first reported, and 2023, 14 cases were reported in the literature. 29% of the cases experienced developmental delay, and 29% expired. The prevalence of MSUD in Korea was estimated to be 1 in 230,000. Of 21 MSUD patients currently being treated at the Korea Genetics Research Center, 19 were detected through newborn screening program, and 2 were diagnosed by the symptoms. 14 MSUD patients had confirmed genetic mutations; 6 (43%) were BCKDHA and 8 (57%) were BCKDHB. In one case, a large deletion was observed. 4 patients had leucine levels above 2,000 (umo/L), and post-dialysis diet therapy was initiated in the newborn period. No patient required further dialysis as diet therapy and regular monitoring proved highly effective. Most MSUD patients were growing normally; weight and height growth were above the 50th percentile in 76% of the cases while BMI values were higher than normal in 71% of cases. Developmental delays were observed only in 2 cases (10%) and anticonvulsant use in 3 cases (14%). With newborn screening available to all Korean infants, early diagnosis and intervention should allow most patients to remain asymptomatic. However, ongoing surveillance, dietary management and continued patient compliance as well as rapid correction of acute metabolic decompensations remain critical to a favorable long-term prognosis.

• The Korean Journal of Food And Nutrition
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• v.22 no.3
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• pp.416-420
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• 2009

A formula diet based on pork meat oligopeptides(pork meat protein hydrolysates) was designed for experimental hepatitic rats. The rats were given D-galactosamine for 6 days. During this period, the rats were provided with a 12% casein diet or the formula diet which was low in aromatic amino acids and rich in branched chain amino acids. The formula diet was prepared using pork meat oligopeptides as the principal nitrogen source. The hepatitic rats given the formula diet had lower plasma GOT and GPT concentrations. Additionally, the fischer ratio of the plasma was significantly lower in those rats. However, there was no significant difference in the plasma insulin-like growth factor-I concentration before and after acid-ethanol extraction among groups. These results suggest that the formula diet was better for the animals than the casein diet. Furthermore, these findings suggest that pork meat oligopeptides are an excellent material for preparation of formula diets for patients suffering from hepatitis.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.7
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• pp.1022-1028
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• 2016

Milk composition is an imperative aspect which influences the quality of dairy products. The objective of study was to compare the chemical composition, nitrogen fractions and amino acids profile of milk from buffalo, cow, sheep, goat, and camel. Sheep milk was found to be highest in fat ($6.82%{\pm}0.04%$), solid-not-fat ($11.24%{\pm}0.02%$), total solids ($18.05%{\pm}0.05%$), protein ($5.15%{\pm}0.06%$) and casein ($3.87%{\pm}0.04%$) contents followed by buffalo milk. Maximum whey proteins were observed in camel milk ($0.80%{\pm}0.03%$), buffalo ($0.68%{\pm}0.02%$) and sheep ($0.66%{\pm}0.02%$) milk. The non-protein-nitrogen contents varied from 0.33% to 0.62% among different milk species. The highest r-values were recorded for correlations between crude protein and casein in buffalo (r = 0.82), cow (r = 0.88), sheep (r = 0.86) and goat milk (r = 0.98). The caseins and whey proteins were also positively correlated with true proteins in all milk species. A favorable balance of branched-chain amino acids; leucine, isoleucine, and valine were found both in casein and whey proteins. Leucine content was highest in cow ($108{\pm}2.3mg/g$), camel ($96{\pm}2.2mg/g$) and buffalo ($90{\pm}2.4mg/g$) milk caseins. Maximum concentrations of isoleucine, phenylalanine, and histidine were noticed in goat milk caseins. Glutamic acid and proline were dominant among non-essential amino acids. Conclusively, current exploration is important for milk processors to design nutritious and consistent quality end products.

• Microbiology and Biotechnology Letters
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• v.26 no.1
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• pp.45-49
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• 1998

Two kinds of Mutants of Corynebacterium glutamicum, which were resistant to branched chain amino acid analogues, were obtained for L-leucine production; C. glutamicum LT26 resistant to 4-azaleucine and $\alpha$-amino-$eta$-hydroxyvaleric acid, and from which C. glutamicum LT3811-70 resistant to DL-4-thiaisoleucine were derived. Accumulation of L-leucine in the culture broths of these mutant strains, C. glutamicum LT26 and LT3811-70, were much higher than those of their parent strains even though they were non-auxotrophic mutants. Enzymatic analyses were performed to measure the activities of $\alpha$-acetohydroxy acid synthase (AHAS) and $\alpha$-isopropylmalate synthase (IPMS), which were the key enzymes for the L-isoleucine, L-valine and L-leucine biosynthetic pathways branching from a common precursor. In C. glutamicum LT26 and LT3811-70, AHAS and IPMS were found to be derepressed and desensitized to L-leucine. In addition, in C. glutamicum LT3811-70, IPMS was further more derepressed by L-leucine and AHAS was more desensitized by L-isoleucine and L-valine compared to its parent strain, C. gIEitamicum LT26.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.8
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• pp.1172-1185
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• 2019

Objective: Meat quality attributes in postmortem muscle tissues depend on skeletal muscle metabolites. The objective of this study was to determine the key metabolic compounds and pathways that are associated with postmortem aging and beef quality in Japanese Black cattle (JB; a Japanese Wagyu breed with highly marbled beef). Methods: Lean portions of Longissimus thoracis (LT: loin) muscle in 3 JB steers were collected at 0, 1, and 14 days after slaughter. The metabolomic profiles of the samples were analyzed by capillary electrophoresis time-of-flight mass spectrometry, followed by statistical and multivariate analyses with bioinformatics resources. Results: Among the total 171 annotated compounds, the contents of gluconic acid, gluconolactone, spermidine, and the nutritionally vital substances (choline, thiamine, and nicotinamide) were elevated through the course of postmortem aging. The contents of glycolytic compounds increased along with the generation of lactic acid as the beef aging progressed. Moreover, the contents of several dipeptides and 16 amino acids, including glutamate and aromatic and branched-chain amino acids, were elevated over time, suggesting postmortem protein degradation in the muscle. Adenosine triphosphate degradation also progressed, resulting in the generation of inosine, xanthine, and hypoxanthine via the temporal increase in inosine 5'-monophosphate. Cysteine-glutathione disulfide, thiamine, and choline increased over time during the postmortem muscle aging. In the Kyoto encyclopedia of genes and genomes database, a bioinformatics resource, the postmortem metabolomic changes in LT muscle were characterized as pathways mainly related to protein digestion, glycolysis, citric acid cycle, pyruvate metabolism, pentose phosphate metabolism, nicotinamide metabolism, glycerophospholipid metabolism, purine metabolism, and glutathione metabolism. Conclusion: The compounds accumulating in aged beef were shown to be nutritionally vital substances and flavor components, as well as potential useful biomarkers of aging. The present metabolomic data during postmortem aging contribute to further understanding of the beef quality of JB and other breeds.