Glutamate transport, mitochondrial

Polarographic studies can also be used to screen for much more specific defects suspected in some patients, such as impaired mitochondrial glutamate transport in cultured skin fibroblasts from patients presenting with neonatal myoclonic epilepsy [64]. 

Keller JN, Mark RJ, Bruce AJ, Blanc E, Rothstein JD, Uchida K, Waeg G, Mattson MP (1997) 4-Hydroxynonenal, an aldehydic product of membrane Upid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes. Neuroscience 80 685-696 Keller JN, Schmitt FA, Scheff SW, Ding Q, Chen Q, Butterfield DA, Markesbery WR (2005) Evidence of increased oxidative damage in subjects with nuld cognitive impairment. Neurology 64 1152-1156... 

Palmieri, L., Villa, A. et al (2003) Identification and metabolic role of the mitochondrial aspartate-glutamate transporter in Saccharomyces cerevisiae. 

FIGURE 31-7 Mitochondrial carriers. Ions and small molecules enter the intermembrane space, since the outer mitochondrial membrane is not a significant permeability barrier. However, the inner mitochondrial membrane is impermeable to ions except those for which there are specific carriers. Most of the carriers are reversible, as indicated by two-headed arrows. Compounds transported in one direction are indicated in red. The ATP/ADP translocase and the aspartate-glutamate carrier are both electrophoretic their transport is driven in the direction of the mitochondrial membrane potential, as indicated by red arrows. Glutamine is carried into the matrix by an electroneutral carrier. The unimpaired functioning of mitochondrial carriers is essential for normal metabolism. (Adapted with permission from reference [70].)... 

In the malate shuttle (left)—which operates in the heart, liver, and kidneys, for example-oxaloacetic acid is reduced to malate by malate dehydrogenase (MDH, [2a]) with the help of NADH+HT In antiport for 2-oxogluta-rate, malate is transferred to the matrix, where the mitochondrial isoenzyme for MDH [2b] regenerates oxaloacetic acid and NADH+HT The latter is reoxidized by complex I of the respiratory chain, while oxaloacetic acid, for which a transporter is not available in the inner membrane, is first transaminated to aspartate by aspartate aminotransferase (AST, [3a]). Aspartate leaves the matrix again, and in the cytoplasm once again supplies oxalo-acetate for step [2a] and glutamate for return transport into the matrix [3b]. On balance, only NADH+H"" is moved from the cytoplasm into the matrix ATP is not needed for this. 

The interconversion of o -ketoglutarate to glutamate involves the malate-aspartate shutde. This shuttle translocates a-ketoglutarate from mitochondria into the cytoplasm and then converts it to glutamate by the catalytic action of aspartate aminotransferase (McKenna et al., 2006). As part of the malate-aspartate shuttle, NADH is oxidized during reduction of oxaloacetate to malate. Malate diffuses across the outer mitochondrial membrane (Fig. 1.6). From the intermembrane space, the malate-a-ketoglutarate antiporter in the inner membrane transports malate into the matrix. For every malate molecule entering the matrix compartment, one molecule of... 

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