How are the irreversible reactions of glycolysis bypassed in gluconeogenesis?
The correct answer and explanation is:
In gluconeogenesis, the irreversible reactions of glycolysis are bypassed by specific enzymes that catalyze reactions in the opposite direction, overcoming the energetically unfavorable steps of glycolysis.
The three key irreversible steps in glycolysis are:
- Hexokinase/Glucokinase step (Glucose to Glucose-6-phosphate): In gluconeogenesis, this step is bypassed by the enzyme glucose-6-phosphatase, which hydrolyzes glucose-6-phosphate to glucose. This reaction occurs primarily in the liver and kidneys, where glucose can be released into the bloodstream.
- Phosphofructokinase-1 step (Fructose-6-phosphate to Fructose-1,6-bisphosphate): The bypass of this step involves the enzyme fructose-1,6-bisphosphatase, which catalyzes the dephosphorylation of fructose-1,6-bisphosphate to form fructose-6-phosphate. This step is tightly regulated and is a major control point in gluconeogenesis.
- Pyruvate kinase step (Phosphoenolpyruvate to Pyruvate): This is the final irreversible step of glycolysis, where pyruvate kinase catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate. In gluconeogenesis, this step is bypassed in two steps. First, pyruvate carboxylase converts pyruvate to oxaloacetate in the mitochondria, using ATP. Then, phosphoenolpyruvate carboxykinase (PEPCK) converts oxaloacetate to PEP in the cytoplasm, using GTP.
These bypass reactions are energetically costly. In total, four high-energy phosphate bonds are consumed for every molecule of glucose produced. Gluconeogenesis is regulated by key hormones like glucagon and cortisol, which activate the expression of enzymes like fructose-1,6-bisphosphatase and PEPCK, ensuring that glucose synthesis is promoted when energy is needed.