MCAT Biochemistry
In the metabolic pathway of gluconeogenesis, glucose is synthesized from non-carbohydrate precursors. The main purpose of gluconeogenesis is to maintain normal blood glucose levels in a fasting state, and its main substrates include lactate, derived from anaerobic metabolism, alanine and glutamine, derived from amino acid catabolism, and glycerol, derived from triglyceride catabolism. The process occurs mostly in the liver, but also in the cortex of the kidneys and the small intestinal epithelium, and is generally stimulated by low blood glucose levels and the release of glucagon.
Gluconeogenesis takes place in multiple parts of the cell, including the mitochondria, cytoplasm, and smooth endoplasmic reticulum. The main steps of this process include the conversion of pyruvate to oxaloacetate by pyruvate carboxylase, the conversion of oxaloacetate to malate by malate dehydrogenase, the conversion of malate to oxaloacetate in the cytosol, and the formation of phosphoenolpyruvate (PEP) by PEP carboxykinase. The process continues with various intermediate reactions, leading to the formation of fructose 1,6-bisphosphate, which is then converted to fructose 6-phosphate by fructose bisphosphatase-1 (FBPase 1). Eventually, glucose 6-phosphate is produced and ultimately turned into glucose by glucose-6-phosphatase.
Lesson Outline
<ul> <li>Introduction to Gluconeogenesis</li> <ul> <li>Metabolic pathway making glucose from non-carbohydrate precursors</li> <li>Purpose: Maintain normal blood glucose levels in a fasting state</li> <li>Main substrates: Lactate, alanine, glutamine, and glycerol</li> </ul> <li>Enzymes and substrates involved</li> <ul> <li>Lactate dehydrogenase: Converts lactate to pyruvate</li> <li>Alanine transaminase: Converts alanine to pyruvate</li> <li>Glutamine enters gluconeogenesis via alpha ketoglutarate</li> <li>All amino acids except leucine and lysine can turn into glucose</li> </ul> <li>Occurrence of Gluconeogenesis</li> <ul> <li>Occurs mostly in the liver</li> <li>Also occurs in the cortex of the kidneys and small intestinal epithelium</li> </ul> <li>Regulation of Gluconeogenesis</li> <ul> <li>Low blood glucose levels stimulate release of glucagon</li> <li>Takes place in mitochondria, cytoplasm, and smooth endoplasmic reticulum</li> </ul> <li>Steps of Gluconeogenesis</li> <ul> <li>1. Pyruvate transported into mitochondrial matrix</li> <li>2. Pyruvate carboxylase adds a CO2 group to make oxaloacetate</li> <li>3. Oxaloacetate is converted into malate via malate dehydrogenase</li> <li>4. Malate exits mitochondria and gets turned back into oxaloacetate</li> <li>5. PEP carboxykinase uses GTP to turn oxaloacetate into PEP</li> <li>6. PEP undergoes series of chemical reactions, eventually making F1,6BP</li> <li>7. FBPase 1 removes phosphate group from F1,6BP to make F6P</li> <li>8. Phosphoglucose isomerase transforms F6P to G6P</li> <li>9. Glucose-6-phosphatase turns G6P into glucose</li> </ul> <li>Energy requirements of Gluconeogenesis</li> <ul> <li>4 ATP, 2 GTP, and 2 NADH are needed to turn 2 pyruvate into 1 glucose</li> <li>Approximately 11 ATP equivalents needed</li> </ul> </ul>
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FAQs
Gluconeogenesis is a metabolic pathway that generates glucose from non-carbohydrate precursors, such as lactate, certain amino acids, and glycerol. This process is essential for maintaining blood glucose levels, especially during periods of fasting or prolonged exercise. By generating glucose from alternative sources, gluconeogenesis prevents hypoglycemia, a condition characterized by abnormally low blood glucose levels, which can lead to severe health complications.
Three major non-carbohydrate precursors are primarily used in gluconeogenesis: lactate, amino acids (particularly alanine and glutamine), and glycerol. Lactate is derived from anaerobic metabolism when oxygen is scarce, while alanine and glutamine are generated from amino acid catabolism. Glycerol, on the other hand, is produced during triglyceride catabolism in adipose tissue. These precursors are then converted into glucose through a series of biochemical reactions in the liver and, to a lesser extent, the kidneys.
Lactate, which is produced during anaerobic metabolism, is a crucial precursor in the gluconeogenesis pathway. During intense physical activity or in conditions when oxygen supply is limited, cells undergo anaerobic metabolism to produce energy. This process generates lactate as a byproduct. The liver can then convert lactate into glucose through the Cori cycle, replenishing the blood glucose levels to fuel bodily functions and preventing hypoglycemia.
Alanine and glutamine, produced during amino acid catabolism, serve as important precursors in the gluconeogenesis pathway. When the body needs glucose and glycogen stores are depleted, it breaks down proteins to release amino acids. Alanine and glutamine are among the most abundant catabolized amino acids, and they can be readily converted into glucose in the liver through a series of biochemical reactions. This process helps maintain blood glucose levels and provides energy during periods of fasting or prolonged exercise.
Glycerol, generated from triglyceride catabolism in adipose tissue, is another key precursor in gluconeogenesis. During periods of fasting or prolonged exercise, the body relies on stored fats as an energy source. The breakdown of triglycerides releases glycerol and fatty acids. While fatty acids are used as an energy source, glycerol is transported to the liver, where it enters the gluconeogenesis pathway and is converted into glucose. This newly-formed glucose can then be released into the bloodstream, helping maintain blood glucose levels and prevent hypoglycemia.
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