7.4. The inclusion of fructose and galactose
In glycolysis
The inclusion of fructose in metabolism in the liver begins with phosphorylation reaction catalyzed by the formation of fructose-1-phosphate:
Fructose-1-phosphate is split by aldolase on glyceraldehyde and dihydroxyacetone phosphate. Dihydroxyacetone phosphate is included in the fifth reaction of glycolysis.
Glyceraldehyde may be included in glycolysis after its phosphorylation with ATP. The resulting glyceraldehyde-3-phosphate is included in the sixth reaction of glycolysis.
Fructose metabolism in muscle, kidney, and adipose tissue begins with its phosphorylation by hexokinase and ATP involvement. Fructose-6-phosphate is formed. The reaction is inhibited by glucose. Next, fructose-6-phosphate is converted to fructose-1,6-bisphosphate and is included in the fourth reaction of glycolysis.
Galactose is produced in the intestine by hydrolysis of lactose. To convert galactose into glucose, it is necessary to carry out the reaction of epimerization. This reaction in the cell is only possible with uridine diphosphate-derivative of galactose (UDP-galactose). Initially, galactose is phosphorylated. Galactose-1-phosphate is formed. Then:
Gal-1-P + UDP-G G-1-P + UDP-Gal, enzyme is hexoso-1-phosphate uridyltransferase.
UDP-galactose undergoes epimerisation:
UDP-Gal UDP-G, enzyme is UDP-hexose-4-epimerase.
UDP-G + PPi G-1-P + UTP, enzyme is UDP-glucose-pyrophosphorilase.
G-1-P under the action of phosphoglucomutase is converted into G-6-P and then is included in the second reaction of glycolysis as usual, or G-1-P under the action of phosphatase is converted to glucose.
7.5. 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
2
3
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+).