Alanine metabolism, transport, and cycling in the brain

Abstract

Brain glutamate/glutamine cycling is incomplete without return of ammonia to glial cells. Previous studies suggest that alanine is an important carrier for ammonia transfer. In this study, we investigated alanine transport and metabolism in Guinea pig brain cortical tissue slices and prisms, in primary cultures of neurons and astrocytes, and in synaptosomes. Alanine uptake into astrocytes was largely mediated by system L isoform LAT2, whereas alanine uptake into neurons was mediated by Na(+)-dependent transporters with properties similar to system B(0) isoform B(0)AT2. To investigate the role of alanine transport in metabolism, its uptake was inhibited in cortical tissue slices under depolarizing conditions using the system L transport inhibitors 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid and cycloleucine (1-aminocyclopentanecarboxylic acid; cLeu). The results indicated that alanine cycling occurs subsequent to glutamate/glutamine cycling and that a significant proportion of cycling occurs via amino acid transport system L. Our results show that system L isoform LAT2 is critical for alanine uptake into astrocytes. However, alanine does not provide any significant carbon for energy or neurotransmitter metabolism under the conditions studied.

Functional characterization of tyrosine transport in fibroblast cells from healthy controls

“…Combination of alanine and NEM, specific inhibitors for system-A, LAT2, LAT3 and LAT4 isoforms inhibited the tyrosine uptake by only 51% (Table 1), indicating that LAT1 isoform is also involved in transport of alanine in equivalent percentage in human fibroblasts. Recent studies conducted with animal brain-astrocytes have mentioned that, the LAT2 isoform as a candidate mediator of Na + -independent alanine uptake, and the role of LAT1 in alanine transport was not conclusively determined [7]. The results of this study indicate that the LAT1 isoform is also probably involved in transport of alanine, approximately 51% in human fibroblasts.…”

Functional characterization of tyrosine transport in fibroblast cells from healthy controls

“…Combination of alanine and NEM, specific inhibitors for system-A, LAT2, LAT3 and LAT4 isoforms inhibited the tyrosine uptake by only 51% (Table 1), indicating that LAT1 isoform is also involved in transport of alanine in equivalent percentage in human fibroblasts. Recent studies conducted with animal brain-astrocytes have mentioned that, the LAT2 isoform as a candidate mediator of Na + -independent alanine uptake, and the role of LAT1 in alanine transport was not conclusively determined [7]. The results of this study indicate that the LAT1 isoform is also probably involved in transport of alanine, approximately 51% in human fibroblasts.…”

Identification of hub genes and potential mechanisms that linked hyperbaric oxygen therapy to traumatic injury Using Bioinformatics Analysis

“…PECAM1 was mainly enriched in betaalanine metabolism. MMP9 was mainly involved in the biosynthesis of unsaturated fatty acids [39]. Herein, we revealed its association with hyperbaric oxygen therapy and TBI; therefore, our ndings provide new evidence for the functions of these three genes.…”

Impact of Inhibition of Glutamine and Alanine Transport on Cerebellar Glial and Neuronal Metabolism

“…We could also confirm an important role of alanine in the return of amino groups from neurons to glial cells [ 9 ]. Regarding the expression of general amino acid transporters, we found little difference between GABAergic and glutamatergic cells; glial cells however have a transporter signature distinct from neurons.…”

Functional characterization of tyrosine transport in fibroblast cells from healthy controls

“…Combination of alanine and NEM, specific inhibitors for system-A, LAT2, LAT3 and LAT4 isoforms inhibited the tyrosine uptake by only 51% (Table 1), indicating that LAT1 isoform is also involved in transport of alanine in equivalent percentage in human fibroblasts. Recent studies conducted with animal brain-astrocytes have mentioned that, the LAT2 isoform as a candidate mediator of Na + -independent alanine uptake, and the role of LAT1 in alanine transport was not conclusively determined [7]. The results of this study indicate that the LAT1 isoform is also probably involved in transport of alanine, approximately 51% in human fibroblasts.…”

Identification of hub genes and potential mechanisms that linked hyperbaric oxygen therapy to traumatic injury Using Bioinformatics Analysis

“…PECAM1 was mainly enriched in betaalanine metabolism. MMP9 was mainly involved in the biosynthesis of unsaturated fatty acids [39]. Herein, we revealed its association with hyperbaric oxygen therapy and TBI; therefore, our ndings provide new evidence for the functions of these three genes.…”

Impact of Inhibition of Glutamine and Alanine Transport on Cerebellar Glial and Neuronal Metabolism

“…We could also confirm an important role of alanine in the return of amino groups from neurons to glial cells [ 9 ]. Regarding the expression of general amino acid transporters, we found little difference between GABAergic and glutamatergic cells; glial cells however have a transporter signature distinct from neurons.…”

Functional characterization of tyrosine transport in fibroblast cells from healthy controls

“…Combination of alanine and NEM, specific inhibitors for system-A, LAT2, LAT3 and LAT4 isoforms inhibited the tyrosine uptake by only 51% (Table 1), indicating that LAT1 isoform is also involved in transport of alanine in equivalent percentage in human fibroblasts. Recent studies conducted with animal brain-astrocytes have mentioned that, the LAT2 isoform as a candidate mediator of Na + -independent alanine uptake, and the role of LAT1 in alanine transport was not conclusively determined [7]. The results of this study indicate that the LAT1 isoform is also probably involved in transport of alanine, approximately 51% in human fibroblasts.…”

Identification of hub genes and potential mechanisms that linked hyperbaric oxygen therapy to traumatic injury Using Bioinformatics Analysis

“…PECAM1 was mainly enriched in betaalanine metabolism. MMP9 was mainly involved in the biosynthesis of unsaturated fatty acids [39]. Herein, we revealed its association with hyperbaric oxygen therapy and TBI; therefore, our ndings provide new evidence for the functions of these three genes.…”

Impact of Inhibition of Glutamine and Alanine Transport on Cerebellar Glial and Neuronal Metabolism

“…We could also confirm an important role of alanine in the return of amino groups from neurons to glial cells [ 9 ]. Regarding the expression of general amino acid transporters, we found little difference between GABAergic and glutamatergic cells; glial cells however have a transporter signature distinct from neurons.…”