Glycerol-3-phosphate shuttle

The glycerol-3-phosphate shuttle system is a biochemical transport mechanism in eukaryotes that is used to transport the reducing agent produced during glycolysis in the form of nicotinamide adenine dinucleotide (NADH) from the cytosol into the matrix of the mitochondria . There the electrons are transferred to ubiquinone and thus fed into the respiratory chain , where they are used to generate adenosine triphosphate (ATP). This regenerates NAD ⁺ and is available again for further metabolic processes.

This shuttle runs much faster than the malate-aspartate shuttle and is therefore primarily used in muscle cells and in the brain, where energy has to be available quickly.

background

Oxidations take place in the cytosol of eukaryotic cells through catabolic processes, for example in glycolysis . Electrons that are released are transferred to NAD ⁺ , so that NADH / H ⁺ is created. These reduction equivalents are also formed in the course of the citric acid cycle , the citric acid cycle taking place in the matrix of the mitochondrion. For further energy generation, the electrons of these reduction equivalents are fed into the respiratory chain and finally transferred to oxygen (aerobic respiration).

The inner membrane of the mitochondria is not permeable to NADH or NAD ⁺ , nor to ATP, ADP and protons . This would result in two problems: On the one hand, the NADH formed in the cytosol cannot diffuse into the matrix of the mitochondrion in order to feed its electrons into the respiratory chain there. Since this regenerates NADH to NAD ⁺ , NAD ⁺ could not get from the matrix into the cytosol in order to further participate in catabolic processes there. In the example of glycolysis, this would quickly come to a standstill, as the amount of NAD ⁺ in the cytosol is limited.

However, two shuttle processes ensure that the electrons stored in the NADH are transported into the mitochondria and this is thereby regenerated to NAD ⁺ . This is the only way to balance the reduction equivalents between the cytosol and mitochondria. One of these shuttles is the glycerol-3-phosphate shuttle system and is shown below.

Occurrence

The shuttle system was found in animals, mushrooms and also plants.

mechanism

Scheme of the glycerine-3-phosphate shuttle. Please refer to the text for details. Abbreviations: ( 1 ) glycerol-3-phosphate; ( 2 ) dihydroxyacetone phosphate; cGPD cytosolic glycerol-3-phosphate dehydrogenase; mGPD mitochondrial glycerol-3-phosphate dehydrogenase; Cyt cytosol; IMR intermembrane space.

In the cytosol, dihydroxyacetone phosphate (DHAP) is reduced to glycerol-3-phosphate . Here, NADH / H ⁺ to NAD ⁺oxidized . This reaction is catalyzed by a soluble, NADH / H ⁺ -dependent cytosolic glycerol-3-phosphate dehydrogenase (cGPD, EC 1.1.1.8 ). In a second step, the glycerol-3-phosphate is oxidized again to dihydroxyacetone phosphate on the inner mitochondrial membrane. The electrons and protons that are released again are transferred to the enzyme-bound flavin-adenine-dinucleotide (FAD), which is thereby reduced to FADH ₂ . This reaction catalyzes a membrane-bound, FAD-dependent mitochondrial glycerol-3-phosphate dehydrogenase (mGPD, EC 1.1.5.3 ). This FADH ₂ is oxidized again to FAD, whereby ubiquinone of the inner mitochondrial membrane is reduced. The latter passes the electrons on to complex III in the respiratory chain.

The complex I of the respiratory chain is skipped in this shuttle, so that in the balance per FADH ₂ are formed only 1.5 units ATP (with NADH / H ⁺ are there 2.5). When using this transport system in contrast to the malate-aspartate shuttle , the energy yield from the complete oxidation of a molecule of glucose is therefore somewhat lower, it is only 30 ATP instead of an average of 32 ATP.

Individual evidence

↑ Ansell, R. et al. (1997): The two isoenzymes for yeast NAD ⁺ -dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox regulation . In: EMBO J. 16 (9); 2179-2187; doi: 10.1093 / emboj / 16.9.2179 , PMID 9171333 , PMC 1169820 (free full text).
↑ Shen, W. et al. (2006): Involvement of a glycerol-3-phosphate dehydrogenase in modulating the NADH / NAD ⁺ ratio provides evidence of a mitochondrial glycerol-3-phosphate shuttle in Arabidopsis . In: Plant Cell 18 (2); 422-441; doi: 10.1105 / tpc.105.039750 , PMID 16415206 , PMC 1356549 (free full text).

[1] Ansell, R. et al. (1997): The two isoenzymes for yeast NAD ⁺ -dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox regulation . In: EMBO J. 16 (9); 2179-2187; doi: 10.1093 / emboj / 16.9.2179 , PMID 9171333 , PMC 1169820 (free full text).

[2] Shen, W. et al. (2006): Involvement of a glycerol-3-phosphate dehydrogenase in modulating the NADH / NAD ⁺ ratio provides evidence of a mitochondrial glycerol-3-phosphate shuttle in Arabidopsis . In: Plant Cell 18 (2); 422-441; doi: 10.1105 / tpc.105.039750 , PMID 16415206 , PMC 1356549 (free full text).