THE SHUTTLE MECHANISMS

Cytosolic NADH (glycolysis reaction 6) cannot transfer hydrogen to the respiratory chain, because the mitochondrial membrane is impermeable to it. Transport of hydrogen through the membrane occurs with the help of special systems, called "shuttle". Hydrogen is transported through the membrane with the participation of pairs of substrates. On both sides of the mitochondrial membrane there is a specific dehydrogenase.

Glycerol-phosphate shuttle system operates in cells of the white muscle, liver and brain.

Hydrogen from NADH in the cytosol is transferred to dihydroxyacetone phosphate by glycerol-3-phosphate dehydrogenase (NAD-dependent enzyme). The resulting glycerol-3-phosphate is oxidized by the enzyme of mitochondrial inner membrane glycerol-3-phosphate dehydrogenase (FAD-dependent enzyme). Then, protons and electrons from FADH₂ pass to ubiquinone, and further along the respiratory chain.

1 – glyceraldehyde-3-phosphate dehydrogenase;

2 - glycerol-3-phosphatede hydrogenase (cytosolic enzyme);

3 - glycerol-3-phosphate dehydrogenase (mitochondrial enzyme).

Malate-aspartate shuttle system includes malate, cytosolic and mitochondrial malate dehydrogenase. This system is more universal, and works in the cardiac muscle, liver and kidneys.

In the cytoplasm NADH reduses oxaloacetate to malate. Malate is transported across mitochondrial membrane with the carrier help. In matrix malate is oxidized to oxaloacetate by NAD-dependent malate dehydrogenase. Redused NADH gives hydrogen to the mitochondrial respiratory chain.

Oxaloacetate formed from malate cannot go from mitochondria to the cytosol: membrane of mitochondria is impermeable to it. Therefore, oxaloacetate is converted to aspartate, which is transported into the cytosol, where it again turns into oxaloacetate.

Both shuttle systems differ by the number of synthesized ATP. In the first system 2 ATP are formed (hydrogen is introduced into the respiratory chain at the level of ubiquinone). The second system is more energy efficient. It gives 3ATP (hydrogen enters the respiratory chain with the mitochondrial NAD⁺).

CORI CYCLE

Cori cycle (glucose-lactate cycle) has opened a Czech scientist and Nobel Prize winner Theresa Cori.

During intense muscular work and in the absence or insufficient number of mitochondria (e.g., in erythrocytes) glucose undergoes anaerobic glycolysis with lactate formation. When there is the accumulation of lactate in the muscles lactic-acidosis occurs. Sensory nerve endings are irritated, causing pain in the muscles.

Lactate is transferred by blood to the liver and is converted to pyruvate and then into glucose. Glucose synthesis is gluconeogenesis. Then glucose with the blood flow can return to the working muscle. Direction of lactate dehydrogenase reaction in the working muscles and the liver determined by the concentration ratio of reduced and oxidized forms of NAD⁺: ratio of NAD⁺ / NADH in contracting muscle is more than in liver.