PMC:6194691 / 125133-127168 JSONTXT

{"project":"MyTest","denotations":[{"id":"30340614-9681479-30706385","span":{"begin":234,"end":237},"obj":"9681479"},{"id":"30340614-11238772-30706386","span":{"begin":239,"end":242},"obj":"11238772"},{"id":"30340614-23104556-30706387","span":{"begin":258,"end":261},"obj":"23104556"},{"id":"30340614-11238772-30706388","span":{"begin":701,"end":704},"obj":"11238772"},{"id":"30340614-28417264-30706389","span":{"begin":706,"end":709},"obj":"28417264"},{"id":"30340614-11238772-30706390","span":{"begin":2030,"end":2033},"obj":"11238772"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"One detailed suggestion (see Fig. 18) is that loss of the branched chain α-ketoacids (BCKA), e.g. α-ketoisocaproate, generated in the transamination in the astrocytes is prevented by using a branched chain amino acid (BCAA) shuttle ([382, 384], reviewed in [385]). In this scheme instead of being further metabolized within the astrocytes as shown in Fig. 17, the BCKA are transferred to neurons where the branched chain amino acids (BCAA), e.g. leucine, can be regenerated by transamination from glutamate producing α-ketoglutarate. The leucine is then exported back to the astrocytes while the glutamate within the neuron is regenerated by glutamate dehydrogenase from NH4+ and the α-ketoglutarate [384, 386]. In this scheme NH4+ is taken from the neuron where it is released from glutamine and will be at relatively high concentration. This is shifted to the astrocyte by the BCAA shuttle where it can be combined with new α-ketoglutarate to complete the de novo synthesis of glutamate. This scheme greatly reduces the need for net flux of BCAA across the blood–brain barrier.\nFig. 18 The branched chain amino acid shuttle for provision of branched chain amino acids (BCAA) in the astrocytes to allow de novo synthesis of glutamate. Leucine (Leu) is used as example of a BCAA. α-KG α-ketoglutarate, α-KIC α-ketoisocaproic acid, Gln glutamine, Glu glutamate, g.a glutaminase, g.d glutamate dehydrogenase, g.s glutamine synthetase, t.a transaminase. Losses of Gln, primarily by efflux, and of Glc, primarily by catabolism are replaced by de novo synthesis of α-KG in astrocytes and transamination using Leu producing α-KIC. Leu is regenerated from α-KIC in the neuron by transamination from Glu producing α-KG. The Glu is in turn regenerated from the α-KG and NH4+ by gdh. Loss of N via efflux of Gln, Glu, and Leu is made good by net inward flux of Leu and NH4+. The BCAA shuttle greatly reduces the need for net inward flux of Leu as this is only required to make good the metabolic loss of α-KIC\n(Based on Figure 1 in Hutson [384])"}

{"project":"2_test","denotations":[{"id":"30340614-9681479-30706385","span":{"begin":234,"end":237},"obj":"9681479"},{"id":"30340614-11238772-30706386","span":{"begin":239,"end":242},"obj":"11238772"},{"id":"30340614-23104556-30706387","span":{"begin":258,"end":261},"obj":"23104556"},{"id":"30340614-11238772-30706388","span":{"begin":701,"end":704},"obj":"11238772"},{"id":"30340614-28417264-30706389","span":{"begin":706,"end":709},"obj":"28417264"},{"id":"30340614-11238772-30706390","span":{"begin":2030,"end":2033},"obj":"11238772"}],"text":"One detailed suggestion (see Fig. 18) is that loss of the branched chain α-ketoacids (BCKA), e.g. α-ketoisocaproate, generated in the transamination in the astrocytes is prevented by using a branched chain amino acid (BCAA) shuttle ([382, 384], reviewed in [385]). In this scheme instead of being further metabolized within the astrocytes as shown in Fig. 17, the BCKA are transferred to neurons where the branched chain amino acids (BCAA), e.g. leucine, can be regenerated by transamination from glutamate producing α-ketoglutarate. The leucine is then exported back to the astrocytes while the glutamate within the neuron is regenerated by glutamate dehydrogenase from NH4+ and the α-ketoglutarate [384, 386]. In this scheme NH4+ is taken from the neuron where it is released from glutamine and will be at relatively high concentration. This is shifted to the astrocyte by the BCAA shuttle where it can be combined with new α-ketoglutarate to complete the de novo synthesis of glutamate. This scheme greatly reduces the need for net flux of BCAA across the blood–brain barrier.\nFig. 18 The branched chain amino acid shuttle for provision of branched chain amino acids (BCAA) in the astrocytes to allow de novo synthesis of glutamate. Leucine (Leu) is used as example of a BCAA. α-KG α-ketoglutarate, α-KIC α-ketoisocaproic acid, Gln glutamine, Glu glutamate, g.a glutaminase, g.d glutamate dehydrogenase, g.s glutamine synthetase, t.a transaminase. Losses of Gln, primarily by efflux, and of Glc, primarily by catabolism are replaced by de novo synthesis of α-KG in astrocytes and transamination using Leu producing α-KIC. Leu is regenerated from α-KIC in the neuron by transamination from Glu producing α-KG. The Glu is in turn regenerated from the α-KG and NH4+ by gdh. Loss of N via efflux of Gln, Glu, and Leu is made good by net inward flux of Leu and NH4+. The BCAA shuttle greatly reduces the need for net inward flux of Leu as this is only required to make good the metabolic loss of α-KIC\n(Based on Figure 1 in Hutson [384])"}