From the Guidelines
Glucagon does not directly regulate the pentose phosphate pathway, the urea cycle, or the tricarboxylic acid cycle (also known as the citric acid cycle or Krebs cycle) in the same way it regulates glycolysis, glycogenesis, and lipogenesis. The enzymes involved in these pathways include:
- Pentose phosphate pathway: glucose-6-phosphate dehydrogenase, 6-phosphogluconolactonase, and 6-phosphogluconate dehydrogenase 1
- Urea cycle: carbamoyl phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinate lyase, and arginase
- Tricarboxylic acid cycle: citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinyl-CoA synthetase, succinate dehydrogenase, fumarase, and malate dehydrogenase These pathways are crucial for various cellular functions, including energy production, nucleotide synthesis, and ammonia detoxification. While glucagon can indirectly influence these pathways through its effects on energy metabolism and cAMP signaling, it does not directly regulate the activity of these enzymes in the same way it regulates glycolysis, glycogenesis, and lipogenesis, as supported by the concept of metabolic promoters that can improve cellular metabolism in a blood glucose-independent way 1.
From the Research
Pathways Unregulated by Glucagon
- The pentose phosphate pathway (PPP) is not directly regulated by glucagon 2, 3
- The Entner-Doudoroff pathway and Calvin cycle, which share reactions with the PPP, may also not be regulated by glucagon, although this is not explicitly stated in the provided evidence
Enzymes of the Unregulated Pathways
- Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the PPP 3
- Other enzymes involved in the PPP include:
- 6-phosphogluconolactonase
- 6-phosphogluconate dehydrogenase
- Ribulose-5-phosphate epimerase
- Ribose-5-phosphate isomerase
- Transketolase
- Transaldolase
- The Entner-Doudoroff pathway involves enzymes such as:
- Glucose-6-phosphate dehydrogenase (also involved in the PPP)
- 6-phosphogluconate dehydratase
- 2-keto-3-deoxy-6-phosphogluconate aldolase
- The Calvin cycle involves enzymes such as:
- Ribulose-1,5-bisphosphate carboxylase/oxygenase
- Phosphoglycerate kinase
- Glyceraldehyde-3-phosphate dehydrogenase
Note: The provided evidence does not explicitly mention the regulation of the Entner-Doudoroff pathway and Calvin cycle by glucagon, so the list of enzymes for these pathways is not exhaustive and is based on general knowledge of these pathways.