BCAA Metabolism and NH3 Homeostasis

Conway, Myra E.; Hutson, Susan M.

doi:10.1007/978-3-319-45096-4_5

Cited by 43 publications

(41 citation statements)

References 125 publications

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“…Regulation of brain Glu is thought to be primarily governed through the Glu/glutamine cycle, where excess Glu remaining after excitation is taken up by astrocytes ( Fig. 2) (reviewed in Conway and Hutson 2016;Yudkoff 2017). At rest, the concentration of Glu in the synaptic cleft is around 0.6 lM (Bouvier et al 1992) but debate exists as to the actual concentration (reviewed in Fetherstone and Shippy 2008).…”

Section: Glutamate/glutamine Cyclementioning

confidence: 99%

Alzheimer’s disease: targeting the glutamatergic system

Conway

2020

Biogerontology

117

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BCATc Cytosolic BCAT BCATm Mitochondrial BCAT BCKA Branched chain a-keto acids BCKD Branched chain a-keto acid dehydrogenase Cho Choline Cr Creatinine Glu Glutamate Glx Glu?glutamine GDH Glutamate dehydrogenase MSUD Maple syrup urine disease NAA N-acetyl aspartate NMDAR N-methyl-D-aspartate receptor NFTs Neurofibrillary tangles PLP Pyridoxal phosphate PSEN1 Presenilin 1 1 H MRS Proton magnetic resonance spectroscopy mI Myoinositol TBI Traumatic brain injury

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Section: Glutamate/glutamine Cyclementioning

confidence: 99%

Alzheimer’s disease: targeting the glutamatergic system

Conway

2020

Biogerontology

117

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“…It is thought that α-KG (potentially through propylhydrylase) activates RagB, driving mTORC1 (Durán et al, 2012). What is interesting is that the human branched chain aminotransferase (hBCAT) protein (hBCAT), which catalyzes the transamination of the branched-chain amino acids (BCAAs) and α-KG to glutamate and their respective α-keto acids (Conway and Hutson, 2016), have not been considered in these proposals. The hBCAT proteins are redox sensitive proteins (Conway et al, 2002, 2004, 2008), which form a metabolon with GDH in their reduced form, but when oxidized catalysis is reversibly inactivated (Islam et al, 2007).…”

Section: Leucine a Dual Role In Mtorc1 And Autophagymentioning

confidence: 99%

Divergent Metabolic Regulation of Autophagy and mTORC1—Early Events in Alzheimer’s Disease?

Shafei

Harris

Conway

2017

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is a progressive disease associated with the production and deposition of amyloid β-peptide (Aβ) aggregates and neurofibrillary tangles, which lead to synaptic and neuronal damage. Reduced autophagic flux has been widely associated with the accumulation of autophagic vacuoles (AV), which has been proposed to contribute to aggregate build-up observed in AD. As such, targeting autophagy regulation has received wide review, where an understanding as to how this mechanism can be controlled will be important to neuronal health. The mammalian target of rapamycin complex 1 (mTORC1), which was found to be hyperactive in AD brain, regulates autophagy and is considered to be mechanistically important to aberrant autophagy in AD. Hormones and nutrients such as insulin and leucine, respectively, positively regulate mTORC1 activation and are largely considered to inhibit autophagy. However, in AD brain there is a dysregulation of nutrient metabolism, linked to insulin resistance, where a role for insulin treatment to improve cognition has been proposed. Recent studies have highlighted that mitochondrial proteins such as glutamate dehydrogenase and the human branched chain aminotransferase protein, through metabolism of leucine and glutamate, differentially regulate mTORC1 and autophagy. As the levels of the hBCAT proteins are significantly increased in AD brain relative to aged-matched controls, we discuss how these metabolic pathways offer new potential therapeutic targets. In this review article, we highlight the core regulation of autophagy through mTORC1, focusing on how insulin and leucine will be important to consider in particular with respect to our understanding of nutrient load and AD pathogenesis.

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“…These amino acids play an important role in the human body for protein synthesis, production of energy and synthesis of many neurotransmitters [1,2]. Moreover, the BCAA contribute to dietary protein intake [3], with animal protein being the main source…”

Section: Introductionmentioning

confidence: 99%

Dietary BCAA Intake Is Associated with Demographic, Socioeconomic and Lifestyle Factors in Residents of São Paulo, Brazil

et al. 2017

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Background: Identifying which risk groups have a higher intake of branched chain amino acids (BCAA) is important for the planning of public policies. This study was undertaken to investigate BCAA consumption, the foods contributing to that consumption and their association with demographic, socioeconomic and lifestyle factors. Methods: Data from the Health Survey of São Paulo, a cross-sectional population-based survey (n = 1662; age range 12–97 years), were used. Dietary intake was measured using 24-h dietary recalls. Baseline characteristics were collected. Associations between BCAA intake and demographic, socioeconomic and lifestyle factors were determined using linear regression. Results: Total BCAA intake was 217.14 mg/kg·day (Leu: 97.16 mg/kg·day; Ile: 56.44 mg/kg·day; Val: 63.54 mg/kg·day). BCAA intake was negatively associated with female sex in adolescents and adult groups, with no white race in adolescents, and with former smoker status in adults. Conversely, BCAA was positively associated with household per capita income in adolescents and adults. No associations were observed in the older adults group. Main food contributors to BCAA were unprocessed red meat, unprocessed poultry, bread and toast, beans and rice. Conclusions: Adolescents and adults were the most vulnerable to having their BCCA intake influenced by demographic, socioeconomic and lifestyle factors.

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BCAA Metabolism and NH3 Homeostasis

Cited by 43 publications

References 125 publications

Alzheimer’s disease: targeting the glutamatergic system

Alzheimer’s disease: targeting the glutamatergic system

Divergent Metabolic Regulation of Autophagy and mTORC1—Early Events in Alzheimer’s Disease?

Dietary BCAA Intake Is Associated with Demographic, Socioeconomic and Lifestyle Factors in Residents of São Paulo, Brazil

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