7.9: Gluconeogenesis
The anabolic counterpart to glycolysis is gluconeogenesis. This occurs mostly in the cells of the liver and kidney. It is an anabolic pathway that synthesizes glucose from non-carbohydrate sources such as lactate, amino acids, oxaloacetate, glycerol and pyruvate. Amino acids are derived from protein digestion and glycerol is obtained from digestion of triglycerides (fats). This is an important pathway because the brain and red blood cells can only use glucose as fuel. Pyruvate is the end product of glycolysis and oxaloacetate can be diverted from the citric acid cycle. This pathway is generally only active during periods of intense exercise or starvation. While glycolysis and gluconeogenesis share many common intermediates, they are not exact opposites. The two precess are summarized below in Figure \(\PageIndex{1}\).
In seven of the eleven reactions of gluconeogenesis (starting from pyruvate), many of the same enzymes are used as in glycolysis, but the reaction directions are reversed.
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There are 3 steps in glycolysis that are so exothermic in the forward direction that they are practically impossible in the reverse direction.
- Phosphoenolpyruvate (PEP) is much higher in energy than pyruvate and therefore the last step of glycolysis cannot simply be reversed (too much energy required). To accomplish this conversion, Gluconeogenesis proceeds via oxaloacetate. Recall that oxaloacetate is an intermediate in the Citric Acid Cycle. This conversions to oxaloacetate use one ATP. The oxaloacetate intermediate is then converted to phosphoenolpyruvate (PEP) which requires one GTP.
- The conversion of 3-phosphoglycerate to 1,3-bisphosphoglycerate is coupled to ATP
- The conversion of 1,3-bisphosphoglycerate to glyceraldehyde-3-phosphate requires NADH.
- Steps 9 and 11 of Gluconeogenesis are reverse of steps 1 and 3 of glycolysis. These steps involve the conversion of fructose 1,6-bisphosphate to fructose-6-phosphate and conversion of glucose-6-phosphate to glucose. The compounds are identical in both processes, but the enzymes are different and no ATP is required.
Remember the 3-carbon stage of Gluconeogenesis is also multiplied by 2
The overall reaction of conversion of pyruvate to glucose is shown below:
\[\ce{2 pyruvate + 4ATP + 2GTP + 2NADH → glucose + 4ADP + 2GDP + 2NAD^{+}} \nonumber\]
The reaction requires the equivalent of \(\ce{6ATP}\) and \(\ce{2NADH}\) and hence is an anabolic process (build up). GTP is considered to be equivalent to ATP in terms of energy.