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  Indian J Med Microbiol
 

Figure 1: Pathological mechanism of glutaric acidemia type 1. Blockage of Lys catabolism due to GCDH deficiency (1) leading to accumulation of GA and 3OHGA (2). GA inhibits the Krebs cycle and mitochondrial function (3) causing increased ROS (4). In the synaptic cleft, the high concentrations of GA and 3OHGA inhibit glutamate uptake (5). increasing glutamate availability. 3OHGA overstimulates AMPA and NMDA (6). This excitotoxic environment associated with changes in astrocyte function and astrogliosis leads to neuronal damage Abbreviations: 3-OHGA, 3-hydroxyglutaric acid; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; GA, glutaric acid; GCDH, glutaryl-CoA dehydrogenase; GLUT, glutamate transporter; H-Lys, hydroxylysine; Lys, lysine; NMDA, N-methyl-d-aspartate; ROS, reactive oxygen species; Trp, tryptophan

Figure 1: Pathological mechanism of glutaric acidemia type 1. Blockage of Lys catabolism due to GCDH deficiency (1) leading to accumulation of GA and 3OHGA (2). GA inhibits the Krebs cycle and mitochondrial function (3) causing increased ROS (4). In the synaptic cleft, the high concentrations of GA and 3OHGA inhibit glutamate uptake (5). increasing glutamate availability. 3OHGA overstimulates AMPA and NMDA (6). This excitotoxic environment associated with changes in astrocyte function and astrogliosis leads to neuronal damage
Abbreviations: 3-OHGA, 3-hydroxyglutaric acid; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; GA, glutaric acid; GCDH, glutaryl-CoA dehydrogenase; GLUT, glutamate transporter; H-Lys, hydroxylysine; Lys, lysine; NMDA, N-methyl-d-aspartate; ROS, reactive oxygen species; Trp, tryptophan