Glycolysis vs Gluconeogenesis PDF

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Summary

Compare and contrast the biochemical pathways of glycolysis and gluconeogenesis....

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Compare and contrast the biochemical pathways of glycolysis and gluconeogenesis. Glycolysis and gluconeogenesis are reciprocal pathways, basically the opposite of one another and are regulated so that while one is active the other is not. Gluconeogenesis and essentially the reverse reactions of glycolysis catalysed by the same enzymes save for three irreversible steps that must be worked around. The initial step in glycolysis is the phosphorylation of glucose to glucose-6-phosphate by the enzyme hexokinase or glucokinase in the liver. This reaction uses up one molecule of ATP. It is an important reaction because it “locks” the glucose in the cell as G6P cannot leave the cell. The reaction is irreversible and therefore gluconeogenesis cannot use the same enzyme. The gluconeogenic reaction is the transformation of glucose-6-phosphate to glucose by the enzyme glucose phosphatase. This reaction takes place on the mitochondrial outer membrane as this is the only location of that enzyme. The next step in glycolysis is the isomerisation of G6P to fructose-6-phosphate catalysed by glucoisomerase. This reaction is reversible and the gluconeogenic reaction is just the reverse. The next step in glycolysis is the phosphorylation of F6P to fructose-1,6-bisphosphate by the enzyme phosphofructokinase. This reaction is irreversible and uses another molecule of ATP and is a major point of reciprocal control of glycolysis and gluconeogenesis. The reverse gluconeogenic reaction is the dephosphorylation reaction of F-1,6-B to F6P catalysed by the enzyme fructose-1,6-bisphosphatase. The next step in glycolysis is the cleavage of the six carbon F-1,6-P to two three carbon pieces (glyceraldehyde-3-phosphate and dihydroxyacetonephosphate) catalysed by the enzyme aldolase. Only G3P can carry onwards in the pathway and thus DHAP is isomerased to G3P by the enzyme triose phosphate isomerase leaving two molecules of G3P. These reactions are all reversible and thus are the same in gluconeogenesis. The next few steps are all reversible and thus are the same in glycolysis and gluconeogenesis except reverse. G3P is oxidised to 1,3-bisphosphoglycerate by the enzyme G3P dehydrogenase and an NADH + H is generated or used depending on reaction direction. 1,3-BPG is then dephosphorylated by phosphogylcerate kinase to 3-phospoglycerate generating two ATP (since there is two molecules). 3-phosphoglycerate is then isomerased to 2-phospoglycerate by phosphoglycerate mutase. The last reversible reaction of glycolysis and gluconeogenesis is the transformation of 2-phosphoglycerate to phosphoenolpyruvate by the enzyme enolase. This reaction uses or generates a molecule of water. The last step of glycolysis and the final irreversible step is the conversion of phosphoenolpyruvate toe pyruvate by the enzyme pyruvate kinase. This reaction generates another two molecules of ATP and is a key point of reciprocal control.

In gluconeogenesis this reaction must be overcome in two steps. The first is the transformation of pyruvate to oxaloacetate by pyruvate carboxylase. This reaction occurs in the mitochondria and OAA must be transferred to the cytosol before gluconeogenesis can take place further. OAA must be converted to malate, sent through the mitochondrial membrance via a receptor and then converted back to OAA (all carried out by malate dehydrogenase both in the mitochondria and cytosol). Then is the conversion of OAA to PEP by phosphoenolpyruvate carboxykinase. This is a decarboxylation that reduces the four carbon OAA back to the two carbon PEP. In conlcusion, glycolysis and gluconeogenesis are reciprocal pathways that cannot be active together. This ensures that the cell is diverting its resources towards the most pressing issue; either the catabolism of glucose to generate energy when nutrient stores are high or converting pyruvate back to glucose when blood levels are low....