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 affect the circulating conc

4 BCAA supplementation tended to decrease the plasma gluco

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

6 BCAAs were quantified via NMR spectroscopy, log-transfor

7 .01) and monocyte chemoattractant protein-1 (BCAA: -0.4% +/- 9%; low-BCAA: 29.0% +/- 18%; P = 0.02) w

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

9 e/proline metabolism, and branched-chain AA (BCAA) metabolism at baseline.

10 plementing VLP diets with branched-chain AA (BCAA) would reverse the negative effects of these diets

11 metabotypes identified a dysregulation in AA/BCAA metabolism that is present in 16.7% of the CAMP sub

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

13 n of an Arabidopsis mutant over-accumulating BCAAs.

14 on the effects of branched-chain amino acid (BCAA) and branched-chain ketoacid (BCKA) ingestion on po

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

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

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

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

19 on, fibrosis, and branched-chain amino acid (BCAA) catabolism; systemic markers of inflammation; and

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

21 borderline plasma branched-chain amino acid (BCAA) concentrations.

22 lites involved in branched-chain amino acid (BCAA) degradation, trimethylamine-N-oxide production, an

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

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

25 core component of branched-chain amino acid (BCAA) metabolism.

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

27 not contribute to branched-chain amino acid (BCAA)-derived aldehyde biosynthesis in melon fruit.

28 ty acid (FFA) and branched-chain amino acid (BCAA).

29 Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is

30 role for impaired branched-chain amino acid (BCAAs; isoleucine, leucine, valine) metabolism in obesit

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

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

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

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

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

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

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

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

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

40 ta2p = 0.31] and branched-chain amino acids (BCAAs) [between-group difference (95% CI): 266 (77, 455)

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

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

43 such as decreased branch chain amino acids (BCAAs) and increased catabolism of tryptophan to the act

44 unclear whether branched-chain amino acids (BCAAs) are a primary input of TOR signaling as they are

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

46 ased circulating branched-chain amino acids (BCAAs) are associated with insulin resistance and type 2

47 Branched chain amino acids (BCAAs) are building blocks for all life-forms.

48 that circulating branched-chain amino acids (BCAAs) are elevated in obese, insulin-resistant individu

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

50 Circulating branched-chain amino acids (BCAAs) associate with insulin resistance and type 2 diab

51 mented with 1.5X branched chain amino acids (BCAAs) by replacing carbohydrate calories (ketogenic).

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

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

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

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

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

57 dysregulation of branched-chain amino acids (BCAAs) may contribute to the behavioral characteristics

58 Altered branched-chain amino acids (BCAAs) metabolism is a distinctive feature of various ca

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

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

61 upplemented with branched-chain amino acids (BCAAs), carbohydrate (maltodextrin), or water for two we

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

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

64 acid proline and branched-chain amino acids (BCAAs), respectively.

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

66 lating levels of branched-chain amino acids (BCAAs), whereas both parameters were normalized by chron

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

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

69 e catabolites of branched-chain amino acids (BCAAs).

70 Branched-chain amino acids (BCAAs, i.e., valine, leucine, and isoleucine) function a

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

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

73 Mechanistically, active BCAA catabolism in BAT is mediated by SLC25A44, which tr

74 In addition, BCAAs and various catabolic products act as signaling mo

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

76 s not known if supplementation of additional BCAAs will further impair glucose metabolism.

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

78 tonomous and non-autonomous roles of altered BCAA metabolism have been implicated in cancer progressi

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

80 erstanding the mechanisms underlying altered BCAA metabolism and how they contribute to disease patho

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

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

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

84 Our study implicates the BCKDH complex and BCAA metabolism in arsenic responses, demonstrating the

85 switched toward utilization of KB, FFA, and BCAA (increased myocardial uptake of these 3 metabolites

86 zation away from glucose toward KB, FFA, and BCAA, thereby improving myocardial energetics, enhancing

87 ty and increases skeletal muscle glucose and BCAA uptake.

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

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

90 lasma PAI-1 concentrations and decreasing AT BCAA catabolism and thereby increasing plasma BCAA conce

91 entage change from supplementation baseline, BCAA: -3.3% +/- 3%; low-BCAA: 10.0% +/- 6%; P = 0.08).

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

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

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

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

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

97 id corresponding to leucine, can assess both BCAA aminotransferase (BCAT) and branched-chain alpha-ke

98 l role in maintaining normal levels of brain BCAAs.

99 erleukin 1beta was significantly elevated by BCAA supplementation (BCAA: 231.4% +/- 187%; low-BCAA: 2

100 18%; P = 0.02) were significantly lowered by BCAA supplementation compared to low-BCAA control.

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

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

103 affect plasma insulin during OGTT challenge (BCAA: -3.9% +/- 8%; low-BCAA: 14.8% +/- 10%; P = 0.28).

104 t that Met may act by decreasing circulating BCAAs levels to favor serotonergic neurotransmission in

105 immunity; thus, we hypothesized circulating BCAAs may be associated with incident obesity-related ca

106 Total circulating BCAAs were unrelated to obesity-related cancer incidence

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

108 rves as a key metabolic filter that controls BCAA clearance via SLC25A44, thereby contributing to the

109 mentation suppressed both without correcting BCAA levels.

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

111 hearts of fasted mice, we observed decreased BCAA-catabolizing enzyme expression and increased circul

112 lation of BCKAs is an indicator of defective BCAA catabolism and has been correlated with glucose int

113 After the BCAA- diet, BCAAs were reduced by 17% during fasting (P < 0.001), by

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

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

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

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

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

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

120 ment of metabolic disease caused by elevated BCAA concentrations.

121 1K (PPM1K) gene has been related to elevated BCAA concentrations and risk of type 2 diabetes.In the p

122 lasma concentrations of nerve growth factor (BCAA: 4.0 +/- 1 pg/mL; low-BCAA: 5.7 +/- 1 pg/mL; P = 0.

123 zymes implicated in the metabolism of KB/FFA/BCAA).

124 ), but returned to baseline values following BCAA and BCKA ingestion (0.024 +/- 0.005%/h and 0.024 +/

125 r understanding of the mechanistic basis for BCAA homeostasis.

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

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

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

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

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

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

132 ve a daily supplement containing either 20 g BCAA or protein low in BCAAs for 4 wk with a 2-wk washou

133 dial increase following the ingestion of 6 g BCAA and BCKA is short-lived, with higher myofibrillar p

134 Ingestion of 6 g BCAA, 6 g BCKA, and 30 g MILK increases myofibrillar pro

135 y was to compare the impact of ingesting 6 g BCAA, 6 g BCKA, and 30 g milk protein (MILK) on the post

136 ly assigned to ingest a drink containing 6 g BCAA, 6 g BCKA, or 30 g MILK.

137 Higher BCAAs and trimethylamine were positively associated with

138 Here we summarize how BCAA metabolic reprogramming is regulated in cancer cell

139 However, BCAA supplementation did not affect plasma insulin durin

140 However, BCAAs were not associated with obesity-related cancers (

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

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

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

144 irculating BCKAs with concomitant changes in BCAA-catabolizing enzyme expression only in the skeletal

145 In turn, a BAT-specific defect in BCAA catabolism attenuates systemic BCAA clearance, BAT

146 iding genetic evidence for their function in BCAA catabolism.

147 a limited proportion of the heritability in BCAA levels.

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

149 ted with the expression of genes involved in BCAA catabolism, in conjunction with an inverse relation

150 ng showed enrichment in proteins involved in BCAA catabolism, ROS metabolism, vesicle trafficking, an

151 tanding of biochemical reactions involved in BCAA catabolism.

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

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

154 standing hypothesis that PDC is involved in BCAA-derived aldehyde formation in fruit.

155 ethionine and alanine, compounds produced in BCAA metabolism and fatty acids, also preceded IA at dif

156 Due to its pivotal role in BCAA metabolism and rapid cellular transport, hyperpolar

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

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

159 Deficiency in BCAAs failed to reverse HFD-induced metabolic impairment

160 ontaining either 20 g BCAA or protein low in BCAAs for 4 wk with a 2-wk washout in between.

161 also lead us to envision that a diet poor in BCAAs, provided either alone or as add-on therapy to con

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

163 olic fingerprints identified by NMR included BCAAs, trimethylamine N-oxide, beta-hydroxybutyrate, tri

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

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

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

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

168 Results for individual BCAA metabolites suggested a modest association for leuc

169 Here, we investigated BCAA metabolism of F98 rat glioma model in vivo using hy

170 1%; low-BCAA: 12.0% +/- 13%), or isoleucine (BCAA: 2.5% +/- 11%; low-BCAA: 7.3% +/- 11%).

171 mixture either containing all AAs or lacking BCAAs.

172 rgo senescence early and overaccumulate leaf BCAAs.

173 ulating concentrations of the BCAAs leucine (BCAA: 9.0% +/- 12%; low-BCAA: 9.2% +/- 11%), valine (BCA

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

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

176 2% +/- 11%), valine (BCAA: 9.1% +/- 11%; low-BCAA: 12.0% +/- 13%), or isoleucine (BCAA: 2.5% +/- 11%;

177 13%), or isoleucine (BCAA: 2.5% +/- 11%; low-BCAA: 7.3% +/- 11%).

178 f the BCAAs leucine (BCAA: 9.0% +/- 12%; low-BCAA: 9.2% +/- 11%), valine (BCAA: 9.1% +/- 11%; low-BCA

179 supplementation (BCAA: 231.4% +/- 187%; low-BCAA: 20.6% +/- 33%; P = 0.05).

180 ementation baseline, BCAA: -3.3% +/- 3%; low-BCAA: 10.0% +/- 6%; P = 0.08).

181 ring OGTT challenge (BCAA: -3.9% +/- 8%; low-BCAA: 14.8% +/- 10%; P = 0.28).

182 ttractant protein-1 (BCAA: -0.4% +/- 9%; low-BCAA: 29.0% +/- 18%; P = 0.02) were significantly lowere

183 ve growth factor (BCAA: 4.0 +/- 1 pg/mL; low-BCAA: 5.7 +/- 1 pg/mL; P = 0.01) and monocyte chemoattra

184 ered by BCAA supplementation compared to low-BCAA control.

185 ein (LP) and LP supplemented with BCAA (LP + BCAA) for 4 weeks.

186 Compared to CON, the LP + BCAA group had higher abundance of Paludibacteraceae and

187 Feeding pigs with LP + BCAA impacted the phenylalanine and protein metabolism a

188 hroughout the study, but those fed with LP + BCAA improved overall FI computed for 4 weeks, tended to

189 Ingestion of MILK, BCAA, and BCKA significantly increased early myofibrilla

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

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

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

193 ion and increased circulating BCKAs, but not BCAAs.

194 More recently, subtle alterations of BCAA metabolism have been suggested to contribute to num

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

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

197 Negative effects of BCAA or methionine were not detectable.

198 pilot study was to determine the effects of BCAA supplementation on glucose metabolism in obese, pre

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

200 We review here the fundamentals of BCAA metabolism in mammalian physiology.

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

202 re; however, increased circulating levels of BCAA are linked to obesity and diabetes.

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

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

205 ns targeting TOR and by examining mutants of BCAA biosynthesis and TOR signaling, we found that BCAA

206 t the importance of organismal regulation of BCAA physiology.

207 vides evidence for FA-mediated regulation of BCAA-catabolizing enzymes and BCKA content and highlight

208 eutic and diagnostic potentials, the role of BCAA metabolism in cancer and the activities of associat

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

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

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

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

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

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

215 Exploratory analyses of BCAAs with individual sites included positive associatio

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

217 We hypothesized that a lower intake of BCAAs improves tissue-specific insulin sensitivity.

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

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

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

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

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

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

224 demonstrate the intracellular production of BCAAs by BCAT1.

225 Short-term dietary reduction of BCAAs decreases postprandial insulin secretion and impro

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

227 Given the role of BCAAs in the regulation of tryptophan influx into the br

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

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

230 le of excess fatty acids (FAs) in perturbing BCAA catabolism and BCKA availability merits investigati

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

232 Plasma BCAA concentration is negatively associated with skeleta

233 Plasma BCAA concentrations increased following test drink inges

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

235 rment depends on disease severity and plasma BCAA concentrations, but cannot be predicted by the amou

236 systemic markers of inflammation; and plasma BCAA concentrations, in 3 groups of participants that we

237 verse relationship between AT pO2 and plasma BCAA concentrations.

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

239 CAA catabolism and thereby increasing plasma BCAA concentrations.TRIAL REGISTRATIONClinicalTrials.gov

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

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

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

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

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

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

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

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

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

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

250 The dietary intervention ensured sufficient BCAA supply above the recommended minimum daily intake.

251 nificantly elevated by BCAA supplementation (BCAA: 231.4% +/- 187%; low-BCAA: 20.6% +/- 33%; P = 0.05

252 efect in BCAA catabolism attenuates systemic BCAA clearance, BAT fuel oxidation and thermogenesis, le

253 dria for thermogenesis and promotes systemic BCAA clearance in mice and humans.

254 Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates

255 iosynthesis and TOR signaling, we found that BCAA over-accumulation leads to up-regulation of TOR act

256 Our data suggest that BCAA supplementation did not impair glucose metabolism i

257 These results demonstrate that BCAAs contribute to plant TOR activation and reveal prev

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

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

260 After the BCAA- diet, BCAAs were reduced by 17% during fasting (P

261 After the BCAA- diet, however, the oral glucose sensitivity index

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

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

264 in all groups, with greater increases in the BCAA and MILK groups compared with the BCKA group (P < 0

265 ncer progression and the key proteins in the BCAA metabolic pathway serve as possible prognostic and

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

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

268 e (3-HIB) is a catabolic intermediate of the BCAA valine.

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

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

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

272 ncreases in the BCKA group compared with the BCAA and MILK groups (P < 0.05).

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

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

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

276 affect the circulating concentrations of the BCAAs leucine (BCAA: 9.0% +/- 12%; low-BCAA: 9.2% +/- 11

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

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

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

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

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

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

283 pathway and mitochondrial enzymes related to BCAA metabolism.

284 AT is mediated by SLC25A44, which transports BCAAs into mitochondria.

285 , both white and brown adipocytes upregulate BCAA utilization and release increasing amounts of 3-HIB

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

287 brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes

288 0% +/- 12%; low-BCAA: 9.2% +/- 11%), valine (BCAA: 9.1% +/- 11%; low-BCAA: 12.0% +/- 13%), or isoleuc

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

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

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

292 se data, we designed a modified HFD in which BCAA dietary supply was reduced by half.

293 shared metabolic phenotypes associated with BCAA dysregulation.

294 were, as a group, negatively correlated with BCAA levels in ASD.

295 Thus, supplementing VLP diets with BCAA temporarily annuls the adverse effects of these die

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

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

298 ), low protein (LP) and LP supplemented with BCAA (LP + BCAA) for 4 weeks.

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

300 ary to evaluate whether supplementation with BCAAs might improve growth in UCDs.