A-Ketoglutarate transporter

Figure21-4. The provision of acetyl-CoA and NADPH for lipogenesis. (PPP, pentose phosphate pathway T, tricarboxylate transporter K, a-ketoglutarate transporter P, pyruvate transporter.)...

The Malate-a-Ketoglutarate Transport System The transport system that conveys malate and a-ketoglutarate across the inner mitochondrial membrane (see Fig. 19-29) is inhibited by n-butylmalonate. Suppose %-butylmalonate is added to an aerobic suspension of kidney cells using glucose exclusively as fuel. Predict the effect of this inhibitor on (a) glycolysis, (b) oxygen consumption, (c) lactate formation, and (d) ATP synthesis. 

Answer The malate-aspartate shuttle transfers electrons and protons from the cytoplasm into the mitochondrion. Neither NAD+ nor NADH passes through the inner membrane, thus the labeled NAD moiety of [7-14C]NADH remains in the cytosol. The 3H on [4-3H]NADH enters the mitochondrion via the malate-aspartate shuttle (see Fig. 19-29). In the cytosol, [4-3H]NADH transfers its 3H to oxaloacetate to form [3H]malate, which enters the mitochondrion via the malate-a-ketoglutarate transporter, then donates the 3H to NAD+ to form [4-3H]NADH in the matrix. 

Figure 2.4. The provision of acetyl-CoA and NADPH for lipogenesis. PPP, pentose phosphate pathway T, tricarboxylate transporter K, a-ketoglutarate transporter. In ruminants, pyruvate dehydrogenase, ATP-citrate lyase and malic enzyme activities are low and perhaps non-functional. (From Murray et al., 1988. Harper s Biochemistry, 21st edn, p. 207, Appleton and Lange, Norwalk, CT reproduced with permission of The McGraw-Hill Companies).

In contrast to the studies of glutamine transport, several studies have suggested a potential role for the malate/a-ketoglutarate transporter in chronic acidosis [135,297]. Although Cheema-Dhadli and Halperin [135] were unable to demonstrate activation of the dicarboxylate (malate/phosphate) transporter in kidney cortex mitochondria from rats with chronic metabolic acidosis, Brosnan et al. [297] demonstrated that the malate/a-ketoglutarate carrier was activated in chronic acidosis. Additional studies are required to characterize this effect fully and to determine its role in the overall process of augmented ammonia formation in metabolic acidosis. However, it is... 

Malate-a-ketoglutarate transporter of mitochondrial inner membrane... 

FIGURE 19-27 Malate-aspartate shuttle. This shuttle for transporting reducing equivalents from cytosolic NADH Into the mitochondrial matrix is used in liver, kidney, and heart. (T) NADH in the cytosol (intermembrane space) passes two reducing equivalents to oxaloacetate, producing malate. (2) Malate crosses the inner membrane via the malate-a-ketoglutarate transporter. In the matrix, malate passes... 

During the process of nutrient assimilation, DIN is first actively transported across the cell membrane. This transport is mediated by species-specific enzymes called permeases that are present in the cell membrane. Once the inorganic nitrogen has crossed the cell membrane, it can participate in anabolic reactions. For example, ammonium helps build amino acids by first reacting with a-ketoglutaric acid to generate glutamic acid ... 

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