What Do You Know About Gluconeogenesis? Trivia Quiz

Glucose is essential for the brain, kidney medulla, red blood cells, retinal cells and any other cells without mitochondria. It cannot be made from acetyl-CoA, and can only be made from any molecule that can be converted to pyruvate. The brain needs a constant supply of glucose to function normally. Fatty acids are unable to be used as a fuel source by the brain since they cannot cross the blood-brain barrier (they are reversibly bound to albumin in the circulation). Ketone bodies can be used as a proportion (40%) of the brain's fuel source, but it still requires a continual supply of glucose. Cells without mitochondria cannot use ketone bodies as fuel.

The liver maintains blood glucose levels by breaking down its glycogen stores to release glucose into the blood but liver glycogen stores are exhausted after 24 hours of fasting. The brain and other cells such as red blood cells must have a constant supply of glucose to function normally. Unlike most other tissues these cells cannot use fatty acids. Fatty acids cannot penetrate the blood-brain barrier; red blood cells lack mitochondria and cannot metabolize them. Gluconeogenesis is the production of glucose. It occurs in the liver in starvation. Glucose is released from glucose-6-phosphate by the enzyme glucose-6-phosphatase. Only liver and kidney have this enzyme though because of its small mass the latter is relatively insignificant in this respect. Amino acids released from muscle protein breakdown are the main source of carbon atoms for gluconeogenesis.

Because it can't be converted back to pyruvate or any other molecule that can be used in gluconeogenesis.

Because this enzyme can be found only in these tissues where is missing from the muscles, so muscles can't release free glucose during gluconeogenesis.

Gluconeogenesis involves a reversal of several glycolytic reactions but there are three reactions that need to be bypassed because of thermodynamic considerations which make them irreversible. These are; the phosphorylation of glucose to glucose-6-phosphate using ATP, the phosphorylation of fructose-6-phosphate to fructose-1:6-bisphosphate, again with ATP. The third is the conversion of phosphoenolpyruvate (PEP) to pyruvate using pyruvate kinase. This forms ATP. In gluconeogenesis, pyruvate is first converted into oxaloacetate by the ATP-dependent pyruvate carboxylase reaction. This is then converted into PEP by PEP carboxykinase using GTP. The PEP is converted to fructose-1:6-bisphosphate then hydrolyzed by fructose-1:6-bisphosphatase. Glucose-6-phosphate is hydrolyzed by glucose-6-phosphatase to release glucose into the blood.

Fatty acids from the hydrolysis of triacylglycerols cannot be used as a carbon source in gluconeogenesis. Fatty acids are oxidized to acetyl-CoA, but the latter cannot be converted to pyruvate, so fatty acids cannot be converted to glucose. Lactate from muscle vigorous muscle activity can be used as a carbon source in gluconeogenesis. It travels via the blood to the liver where it is first converted to pyruvate by lactate dehydrogenase, then to glucose by gluconeogenesis. Glycerol from the hydrolysis of triacylglycerols in adipose cells travels to the liver and is converted to glucose in gluconeogenesis. The enzyme glycerol kinase converts glycerol to glycerol-3-phosphate. It enters the gluconeogenesis pathway via dihydroxyacetone phosphate. Red blood cells can only undergo anaerobic glycolysis since they have no mitochondria so they produce lactate. The lactate travels to the liver where it is converted to pyruvate and is used as a carbon source in gluconeogenesis.

The main source of pyruvate used by the liver for gluconeogenesis is from the breakdown of muscle proteins promoted by the stress hormone cortisol. Several amino acids give rise to citric acid cycle acids and are converted to oxaloacetate. Pyruvate is converted to oxaloacetate by pyruvate carboxylase then to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase. In muscles pyruvate accepts amino groups (from other amino acids), to form alanine which is released into the blood. In the liver, it is converted back to pyruvate for gluconeogenesis.

In gluconeogenesis, the fatty acid breakdown increase will increase the amount of Acetyl Co-A and some of Acetyl Co-A will be converted to ketone bodies.

Ethanol is oxidized to acetaldehyde in the liver cytoplasm by alcohol dehydrogenase. This is oxidized to acetate by acetaldehyde dehydrogenase in the mitochondria. Two NADH molecules are produced in the liver cell from each ethanol molecule. Intake of large amounts of alcohol results in the cellular NADH/NAD+ ratio is increased. Several dehydrogenases such as lactate dehydrogenase can be inhibited by this so that the pyruvate/lactate equilibrium is disturbed resulting in reduced amounts of pyruvate available for gluconeogenesis. Excessive drinking often results in reduced food intake so that dietary sources of glucose diminish. This coupled with impaired gluconeogenesis can result in an inadequate supply of glucose to the brain in extreme cases with dangerous consequences.

Hexokinase is involved in glycolysis, where it phosphorylates glucose to form glucose-6-phosphate, initiating glucose breakdown for energy. It is not involved in gluconeogenesis, which synthesizes glucose from non-carbohydrate sources. In contrast, enzymes like Fructose-1,6-bisphosphatase, Pyruvate carboxylase, and Phosphoenolpyruvate carboxykinase (PEPCK) play critical roles in gluconeogenesis, facilitating various steps to produce glucose.

When plasma glucose levels are high and cellular ATP reserves are adequate, glucose is stored in the form of glycogen or is converted to triglyceride. When plasma glucose levels fall, glycogen is broken down (glycogenolysis) to liberate glucose and glucose is synthesized from non-carbohydrate precursors (gluconeogenesis). The liver carries out both these processes.