ライフサイエンスコーパス: BCAA

1 BCAA homeostasis is controlled by the mitochondrial bran

2 BCAA levels in brain were diminished in both Bdk(-/-) an

3 BCAA supplementation did not alter the respective baseli

4 BCAAs (i.e., isoleucine, leucine, and valine) and their

5 BCAAs increased the affinity of CodY for the ilvB promot

6 We previously identified BrnQ1 as a BCAA transporter, yet a brnQ1 mutant remained capable of

7 ds (AAs), in particular, branched chain AAs (BCAAs), are often found increased in nonalcoholic fatty

8 CodY is a branched-chain amino acid (BCAA) and GTP sensor and a global regulator of transcrip

9 the first step of branched-chain amino acid (BCAA) biosynthesis, a pathway essential to the lifecycle

10 HAS) required for branched-chain amino acid (BCAA) biosynthesis.

11 erons involved in branched-chain amino acid (BCAA) biosynthesis.

12 tical step in the branched-chain amino acid (BCAA) catabolic pathway and has been the focus of extens

13 ormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD.

14 Branched-chain amino acid (BCAA) catabolism is regulated by branched-chain alpha-ke

15 n shown to reduce branched-chain amino acid (BCAA) concentrations in vivo.

16 decreases plasma branched-chain amino acid (BCAA) concentrations, and previous research suggests tha

17 ohydrate (CHO) or branched-chain amino acid (BCAA) feedings may attenuate increases in 5-HT and impro

18 s with either the branched-chain amino acid (BCAA) isoleucine or the BCAA metabolite, propionate, ind

19 nd TFs within the branched chain amino acid (BCAA) metabolic pathway, possibly providing an explanati

20 Branched-chain amino acid (BCAA) metabolism plays a central role in the pathophysio

21 ar model of human branched-chain amino acid (BCAA) metabolism, the distribution, activity, and expres

22 ay for monitoring branched chain amino acid (BCAA) uptake/release dynamics in 3T3-L1 cells.

23 emented with the branched-chain amino acids (BCAA) anaerobically or returned to aerobic growth condit

24 the oxidation of branched-chain amino acids (BCAA) and fatty acids (e.g., carnitine palmitoyltransfer

25 The branched-chain amino acids (BCAA) are essential amino acids required for protein hom

26 acids (BCKA) and branched-chain amino acids (BCAA) in body fluids (e.g. keto-isocaproic acid from the

27 ive reduction in branched-chain amino acids (BCAA) in spite of adequate dietary protein intake.

28 dium lacking the branched-chain amino acids (BCAA) leucine or valine but grows well if isoleucine is

29 enes involved in branched-chain amino acids (BCAA) metabolism.

30 lize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid an

31 , degradation of branched chain amino acids (BCAA), and regulation of peroxisome proliferator activat

32 he catabolism of branched-chain amino acids (BCAA), such as leucine, thereby providing macromolecule

33 of ketogenic and branched-chain amino acids (BCAA).

34 hat branched-chain and aromatic amino acids (BCAAs and AAAs) are closely associated with the risk of

35 of branched-chain and aromatic amino acids (BCAAs and ARO AAs, respectively) and induced expression

36 Branched-chained amino acids (BCAAs) (Leu, Ile, and Val) and their catabolites, propio

37 e in circulating branched-chain amino acids (BCAAs) after weight loss induced by Roux-en-Y gastric by

38 Circulating branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) have been shown t

39 o acids, such as branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), have been associ

40 plasma levels of branched-chain amino acids (BCAAs) are associated with a greater than twofold increa

41 Branched-chain amino acids (BCAAs) are synthesized in plants from branched-chain ket

42 Branched-chain amino acids (BCAAs) are three of the nine essential amino acids in hu

43 The branched-chain amino acids (BCAAs) are vital to both growth and virulence of the hum

44 these tumors use branched-chain amino acids (BCAAs) differently.

45 The branched-chain amino acids (BCAAs) Ile, Val, and Leu are essential nutrients that hu

46 l data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the

47 he limitation of branched-chain amino acids (BCAAs) is a cue that induces the expression of a subset

48 lites, i.e., the branched-chain amino acids (BCAAs) isoleucine, leucine, and valine (ILV) and the nuc

49 The branched-chain amino acids (BCAAs) Leu, Ile, and Val are among nine essential amino

50 oxidation of the branched-chain amino acids (BCAAs) leucine, isoleucine (Ile), and valine (Val) in th

51 The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are elevated in m

52 or a mixture of branched chain amino acids (BCAAs) on myofibrillar protein synthesis (MPS) at rest a

53 Branched chain amino acids (BCAAs) play critical roles in cell and tissue functions

54 atabolism of the branched-chain amino acids (BCAAs) provides nitrogen for the synthesis of glutamate

55 That is, branched-chain amino acids (BCAAs) served as more potent co-activators of CodY-depen

56 The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amin

57 n methionine and branched chain amino acids (BCAAs), apparently reduce liver fat, but can induce insu

58 Therefore, the branched-chain amino acids (BCAAs), especially leucine, are popular as dietary suppl

59 lementation with branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, has s

60 otransferase for branched-chain amino acids (BCAAs), is aberrantly activated and functionally require

61 Branched-chain amino acids (BCAAs), particularly leucine, act as nutrient signals re

62 acids (FAs) and branched-chain amino acids (BCAAs), senses nutrients and promotes mTOR activation an

63 educed levels of branched-chain amino acids (BCAAs), which are associated with insulin resistance in

64 concentration of branched chain amino acids (BCAAs), which are key precursors to de novo glutamate sy

65 he catabolism of branched-chain amino acids (BCAAs).

66 ntial amounts of branched chain amino acids (BCAAs).

67 ors, GTP and the branched-chain amino acids (BCAAs).

68 ng levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strong

69 Branched-chain amino acids (BCAAs; leucine, isoleucine and valine) are elevated in t

70 Here, we describe BcaP as an additional BCAA transporter, and determine that it plays a secondar

71 chanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes.

72 ken together, this work reveals that altered BCAA metabolism activated through the MSI2-BCAT1 axis dr

73 nalyses revealed positive correlations among BCAA catabolism genes in stress, development, diurnal/ci

74 AT1 in glioma pathogenesis, making BCAT1 and BCAA metabolism attractive targets for the development o

75 els of branched-chain keto acids (BCKA), and BCAA in plasma of T2D patients, which may result from th

76 xist to support a beneficial role of CHO and BCAA on brain 5-HT and central fatigue, but the strength

77 differences in proteins involved in fat and BCAA oxidation that might contribute to the accumulation

78 contribute to the accumulation of lipid and BCAA frequently associated with the pathogenesis of insu

79 ate regulation of the ilvB operon by GTP and BCAAs and to bind to the ilvB promoter region.

80 was stronger in the presence of both GTP and BCAAs than of BCAAs alone.

81 P), which differ in levels of methionine and BCAAs, in patients with type 2 diabetes and NAFLD.

82 ng concentrations of the diabetes-associated BCAA valine at 6 mo independent of the weight change.

83 We examined the association between BCAA intake and risk of diabetes in a population-based c

84 rvational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analy

85 adenylate cyclases, FhlA) domain that binds BCAAs and a winged helix-turn-helix (wHTH) domain that b

86 lts demonstrate the consequences of blocking BCAA catabolism during both normal growth conditions and

87 However, higher blood BCAA levels have been associated with insulin resistance

88 ) may contribute significantly to whole-body BCAA metabolism.

89 l role in maintaining normal levels of brain BCAAs.

90 h alcoholic cirrhosis is acutely reversed by BCAA/LEU.

91 ss of BDK function in mice and humans causes BCAA deficiency and epilepsy with autistic features.

92 Wild-type A. pleuropneumoniae grew in CDM+BCAA but not in CDM-BCAA in the presence of sulfonylurea

93 ropneumoniae grew in CDM+BCAA but not in CDM-BCAA in the presence of sulfonylurea AHAS inhibitors.

94 unctions to protect the brain during chronic BCAA deficiency.

95 e, in association with increased circulating BCAA levels.

96 ty of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation

97 tissue BCAA enzymes may modulate circulating BCAA levels.

98 ripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state).

99 of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-

100 RYGB causes the same decline in circulating BCAAs and their C3 and C5 acylcarnitine metabolites.

101 e able to restore growth of Escherichia coli BCAA auxotrophic cells, but SlBCAT1 and -2 were less eff

102 All brain-injured mice that consumed BCAAs demonstrated cognitive improvement with a simultan

103 ly, external supply of dipeptides containing BCAAs and ARO AAs rescues cell proliferation and compens

104 mentation suppressed both without correcting BCAA levels.

105 n source, whereas PDAC tumors have decreased BCAA uptake.

106 This decreases BCAA oxidation rates in adipose tissue, but not in muscl

107 These results suggest that dietary BCAA intervention could promote cognitive improvement by

108 Our results link dietary BCAAs with the regulation of metabolic health and energy

109 Selective reduction of dietary BCAAs also restores glucose tolerance and insulin sensit

110 nowledge, there has been no study on dietary BCAAs and the risk of diabetes.

111 d suggest that specifically reducing dietary BCAAs may represent a highly translatable option for the

112 We find that specifically reducing dietary BCAAs rapidly reverses diet-induced obesity and improves

113 examine the hypothesis that reducing dietary BCAAs will promote weight loss, reduce adiposity, and im

114 During BCAA excess, phosphorylated Ser293 (pSer293) becomes dep

115 stent with the idea that loss of GCN2 during BCAA deficiency compromises glial cell defenses to oxida

116 ment of metabolic disease caused by elevated BCAA concentrations.

117 1K (PPM1K) gene has been related to elevated BCAA concentrations and risk of type 2 diabetes.In the p

118 HAS, but also identified a method to enhance BCAA accumulation in crop plants that will significantly

119 al tract serves to prevent loss of essential BCAA carbon and raises the possibility that the gastroin

120 PP2Cm-deficient mice exhibited BCAA catabolic defects and a metabolic phenotype similar

121 ts of ilvI and lrp were both auxotrophic for BCAA in CDM and attenuated compared to wild-type A. pleu

122 r understanding of the mechanistic basis for BCAA homeostasis.

123 However, the metabolic pathways for BCAA breakdown are largely unknown so far in plants.

124 Bcat1 and Bcat2, the enzymes responsible for BCAA use, impairs NSCLC tumor formation, but these enzym

125 All enzymes were active in the forward (BCAA synthesis) and reverse (branched-chain keto acid sy

126 k resistance mutations caused increased free BCAA levels in both seedlings and seeds.

127 NSCLC tumors incorporate free BCAAs into tissue protein and use BCAAs as a nitrogen so

128 rmed through transfer of an amino group from BCAA to alpha-ketoglutarate in reaction catalyzed by bra

129 yl branched-chain fatty acids (mmBCFAs) from BCAAs.

130 regulating seed amino acid levels, the full BCAA catabolic network is not completely understood in p

131 ry consumption of BCAAs restored hippocampal BCAA concentrations to normal, reversed injury-induced s

132 h testosterone-treated rats showing impaired BCAA metabolism and dysfunctions in ELOVL2, SLC22A4 and

133 is a growing body of literature implicating BCAA metabolism in more common disorders such as the met

134 t with a unique, catabolic role for BCAT2 in BCAA metabolism in seeds.

135 In individuals with deficiencies in BCAA, these amino acids can be preserved through inhibit

136 the mitochondrial SlBCAT1 and -2 function in BCAA catabolism while the chloroplastic SlBCAT3 and -4 f

137 iding genetic evidence for their function in BCAA catabolism.

138 the chloroplastic SlBCAT3 and -4 function in BCAA synthesis.

139 a limited proportion of the heritability in BCAA levels.

140 r affect the expression of genes involved in BCAA biosynthesis, suggesting that S. mutans CodY is not

141 late many genes, including genes involved in BCAA biosynthesis.

142 ding proteins resembling enzymes involved in BCAA catabolism in animals, fungi, and bacteria as well

143 he view that inhibition of genes involved in BCAA handling in skeletal muscle takes place as part of

144 ions in skeletal muscle proteins involved in BCAA metabolism but not in obese mice.

145 We conclude that AtHDH1 has a dual role in BCAA metabolism in plants.

146 D) responsible for the rate-limiting step in BCAA catabolism.

147 h BCAT2 contributing to natural variation in BCAA levels, glutamate recycling, and free amino acid ho

148 Consumption of a Western diet reduced in BCAAs was also accompanied by a dramatic improvement in

149 of the amino acid concentrations, including BCAAs and AAAs, in both trials.

150 pennellii BCAT4, did significantly increase BCAA levels.

151 at only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in

152 a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes.

153 and obese children replicates the increased BCAA and acylcarnitine catabolism and changes in nucleot

154 scles themselves, and most studies involving BCAA show no performance benefits.

155 n in chemically defined medium (CDM) lacking BCAA.

156 rgo senescence early and overaccumulate leaf BCAAs.

157 in amino acid mixture enriched with leucine (BCAA/LEU).

158 A low BCAA diet transiently induces FGF21 (fibroblast growth f

159 tential of phenylbutyrate treatment to lower BCAA and their corresponding alpha-keto acids (BCKA) in

160 DK as a pharmacological approach to mitigate BCAA accumulation in metabolic diseases and heart failur

161 y of type 2 diabetes, and that mitochondrial BCAA management is impaired in skeletal muscle from T2D

162 ich may result from the disruption of muscle BCAA management.

163 for reducing the plasma levels of neurotoxic BCAA and their corresponding BCKA in a subset of MSUD pa

164 Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BC

165 (OTCD) subjects and the possible benefits of BCAA supplementation during phenylbutyrate therapy.

166 rter, yet a brnQ1 mutant remained capable of BCAA acquisition.

167 helial lining fluid showed concentrations of BCAA ranging from 8 to 30 micromol/liter, which is 10 to

168 egulated in CDM containing concentrations of BCAA similar to those found in pulmonary secretions.

169 Negative effects of BCAA or methionine were not detectable.

170 cuses on recent developments in the field of BCAA metabolism.

171 The interface of BCAA metabolism lies with branched-chain aminotransferas

172 aconate synthesis, suggesting involvement of BCAA catabolism through the IRG1/itaconate axis within t

173 rences are reflected in expression levels of BCAA catabolic enzymes in both mice and humans.

174 ther pulmonary pathogens, uses limitation of BCAA as a cue to regulate the expression of genes requir

175 We present an in vivo regulatory model of BCAA homeostasis derived from analysis of feedback-resis

176 acid decarboxylase support a perturbation of BCAA and neurotransmitter metabolism.

177 ue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue.

178 bservations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and in

179 Finally, the role of BCAA in body nitrogen metabolism is discussed.

180 ic study is consistent with a causal role of BCAA metabolism in the aetiology of type 2 diabetes.

181 Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic

182 A core subset of BCAA catabolism genes, including those encoding putative

183 f the enzymes responsible for utilization of BCAA nitrogen limits the growth of lung tumors, but not

184 have increased expression in the absence of BCAAs.

185 result, nutrients induce the accumulation of BCAAs and FAs that activate mTOR signaling and stimulate

186 Severely decreased ECHS1, accumulation of BCAAs and FAs, activation of mTOR and overexpression of

187 Ex vivo application of BCAAs to hippocampal slices from injured animals restore

188 Increased concentrations of BCAAs and odd-chain fatty acids, both of which are metab

189 ver, a reduction in plasma concentrations of BCAAs due to phenylbutyrate treatment was observed.

190 Dietary consumption of BCAAs restored hippocampal BCAA concentrations to normal

191 r findings verified the close correlation of BCAAs and AAAs with insulin resistance and future develo

192 This effect of BCAAs in vitro was additive with the effect of GTP on Co

193 A high intake of BCAAs in terms of percentage of total protein was signif

194 Data suggest that a high intake of BCAAs may be associated with a decrease in the risk of d

195 Postprandial levels of BCAAs and methionine were significantly higher in subjec

196 eering plants that accumulate high levels of BCAAs by simply over-expressing the respective biosynthe

197 that specifically reducing dietary levels of BCAAs has beneficial effects on the metabolic health of

198 n these subunits accumulate higher levels of BCAAs in mature seeds, providing genetic evidence for th

199 gh-sugar Western diet with reduced levels of BCAAs lost weight and fat mass rapidly until regaining a

200 tion of SlBCAT1 resulted in higher levels of BCAAs.

201 ne tolerance and accumulate higher levels of BCAAs.

202 drolysis and is augmented in the presence of BCAAs.

203 demonstrate the intracellular production of BCAAs by BCAT1.

204 study was to evaluate the potential role of BCAAs and AAAs in predicting the diabetes development in

205 n the presence of both GTP and BCAAs than of BCAAs alone.

206 t analysis showed effects of testosterone on BCAA degradation pathway and mitochondrial enzymes relat

207 PC6 (BCAAs and aromatic AAs) and PC10 (asparagine, glycine, a

208 ce that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (

209 However, total and relative amounts of plant BCAAs rarely match animal nutritional needs, and improve

210 Plasma BCAA concentration is negatively associated with skeleta

211 Following oral administration, plasma BCAA concentrations showed a similar increase in patient

212 kidneys, and liver with reduction in plasma BCAA concentrations.

213 f BCKDC with significant reduction in plasma BCAA concentrations.

214 d glucose Rd by ~55%, decreased total plasma BCAA and C3 and C5 acylcarnitine concentrations by 20-35

215 We evaluated plasma BCAAs and their C3 and C5 acylcarnitine metabolites, mus

216 protein accounts for the increase in plasma BCAAs that accompanies early-stage disease.

217 biopsy were associated with increased plasma BCAAs and aromatic AAs and were mildly associated with t

218 We show that plasma BCAAs are also elevated in mice with early-stage pancrea

219 glucose Rd correlated negatively with plasma BCAAs and with C3 and C5 acylcarnitine concentrations (r

220 eived phenylbutyrate and phenylbutyrate plus BCAA supplementation.

221 lated during progression of CML and promotes BCAA production in leukaemia cells by aminating the bran

222 In the present study, we show that a reduced BCAA diet promotes rapid fat mass loss without calorie r

223 er, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial.

224 with an existing metabolic index, Fischer's BCAA/AAA molar ratio, as well as indexes generated using

225 iation study and haplotype analysis for seed BCAA traits in Arabidopsis thaliana revealed a strong as

226 However, seed BCAA levels in major crops are insufficient to meet diet

227 nderstanding of the genetics underlying seed BCAA content and composition.

228 improvement for increased and balanced seed BCAAs an important nutritional target.

229 esponsible for the natural variation of seed BCAAs in this interval.

230 leuropneumoniae mutants unable to synthesize BCAA would be attenuated in a porcine infection model.

231 ese essential nutrients, and they synthesize BCAAs through a conserved pathway that is inhibited by i

232 These results clearly demonstrate that BCAA availability is limited in the lungs and support th

233 Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates

234 We found that BCAA and BCKA are both significantly reduced following p

235 on these observations, we hypothesized that BCAA would be found at limiting concentrations in pulmon

236 se results extend the previous evidence that BCAAs can be catabolized and serve as respiratory substr

237 The BCAA/LEU supplement did not alter myostatin expression,

238 As the BCAA cannot be made de novo in mammals, their cellular c

239 cid dehydrogenase (BCKD) complex commits the BCAA to degradation and thus is vital in controlling the

240 D), an iron-sulphur enzyme essential for the BCAA biosynthesis, is completely inactivated in cells by

241 ations and support an essential role for the BCAA in human brain function.

242 y fluids (e.g. keto-isocaproic acid from the BCAA leucine), leading to numerous clinical features inc

243 se (AHAS), the first committed enzyme in the BCAA biosynthesis pathway.

244 ins interact and the structural basis of the BCAA dependence of this interaction are unknown.

245 ate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endot

246 ed-chain amino acid (BCAA) isoleucine or the BCAA metabolite, propionate, induced MCM mRNA fourfold.

247 redox level of the environment regulates the BCAA biosynthesis pathway.

248 s Analysis provided support to idea that the BCAA genes are relevant in the pathophysiology of type 2

249 ing alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream

250 GTP and the BCAAs were shown to act additively to increase the affin

251 with the global regulatory protein CodY, the BCAAs are key co-regulators of virulence factors.

252 ase (BCKDC) and associated elevations in the BCAAs and their ketoacids have been recognized as the ca

253 ons were optimized for the resolution of the BCAAs isoleucine, leucine, and valine, as well as 13 oth

254 y related to the concurrent reduction of the BCAAs leucine and isoleucine, the AAAs tyrosine and phen

255 ddition to supporting protein synthesis, the BCAAs serve as precursors for branched-chain fatty acids

256 BCAT1 exerts its oncogenic function through BCAA production in blast crisis CML cells.

257 We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is high

258 is, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genet

259 that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

260 ans causes mmBCFA deficiency, in addition to BCAA accumulation.

261 , links the regulation of fatty acid flux to BCAA catabolism, providing a mechanistic explanation for

262 hology of MSUD has been attributed mainly to BCAA accumulation, but the role of mmBCFA has not been e

263 pathway and mitochondrial enzymes related to BCAA metabolism.

264 est in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observation

265 mutants that exhibit enhanced resistance to BCAAs.

266 ed for induction of expression of ilvI under BCAA limitation.

267 orate free BCAAs into tissue protein and use BCAAs as a nitrogen source, whereas PDAC tumors have dec

268 to our understanding of the basis of in vivo BCAA homeostasis and inform approaches to improve the am

269 differences in amino acid accumulation when BCAA catabolism is perturbed.

270 However, the mechanism by which BCAA binding regulates transcriptional changes is not cl

271 than controls (P < 0.05) but increased with BCAA/LEU only in controls (P < 0.001).

272 in patients with cirrhosis was reduced with BCAA/LEU (P = 0.01).

273 Direct supplementation with BCAAs ameliorates the defects caused by BCAT1 knockdown,