29.8 Carbohydrate Biosynthesis: Gluconeogenesis
2 min read•may 7, 2024
is your body's glucose-making machine. When you're low on sugar, it kicks into gear, turning non-carb sources like and amino acids into glucose. This process keeps your blood sugar steady, especially during fasting or long workouts.
The pathway involves a series of enzyme-catalyzed reactions, starting with and ending with glucose. It's not just in reverse - it uses special enzymes to bypass irreversible steps, making sure your body can make glucose when it needs to.
Gluconeogenesis Overview
Purpose of gluconeogenesis
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- Synthesizes glucose from non-carbohydrate precursors (pyruvate, lactate, , )
- Maintains blood glucose levels during fasting or prolonged exercise
- Brain relies on constant glucose supply for energy
- Glucose is primary fuel source for brain, red blood cells, other tissues
- Occurs primarily in and to lesser extent in kidneys
- Upregulated when glycogen stores depleted to produce glucose from non-carbohydrate sources
- Helps maintain normal blood glucose range
Gluconeogenesis Pathway
Steps in gluconeogenesis pathway
- Pyruvate converted to by
- Requires , ATP,
- Oxaloacetate reduced to malate by
- Requires NADH
- Malate oxidatively decarboxylated to (PEP) by
- Requires
- PEP converted to 2-phosphoglycerate by
- 2-phosphoglycerate converted to 3-phosphoglycerate by
- 3-phosphoglycerate converted to 1,3-bisphosphoglycerate by
- Produces ATP
- 1,3-bisphosphoglycerate reduced to glyceraldehyde-3-phosphate by
- Requires NADH
- Glyceraldehyde-3-phosphate converted to by
- Fructose-1,6-bisphosphate dephosphorylated to fructose-6-phosphate by
- Fructose-6-phosphate converted to glucose-6-phosphate by
- Glucose-6-phosphate dephosphorylated to glucose by
Gluconeogenesis vs glycolysis mechanisms
- Gluconeogenesis and glycolysis are reciprocal metabolic pathways
- Glycolysis breaks down glucose to pyruvate and ATP
- Gluconeogenesis synthesizes glucose from non-carbohydrate precursors
- Share several enzymes and intermediates but gluconeogenesis is not simple reversal of glycolysis
- Three irreversible glycolysis steps bypassed by alternative enzymes in gluconeogenesis
- replaced by pyruvate carboxylase and PEP carboxykinase
- replaced by fructose-1,6-bisphosphatase
- replaced by glucose-6-phosphatase
- Bypass of irreversible steps allows gluconeogenesis to be energetically favorable
- Requires input of ATP and GTP energy
- Energy input drives glucose synthesis against concentration gradient
- Reciprocally regulated by hormones
- and stimulate gluconeogenesis, inhibit glycolysis
- stimulates glycolysis, inhibits gluconeogenesis
Metabolic Regulation and Integration
Role in energy metabolism and glucose homeostasis
- Gluconeogenesis plays a crucial role in maintaining
- Regulates between different metabolic pathways
- Utilizes glucogenic amino acids as precursors for glucose synthesis
- Helps recycle amino acid carbon skeletons for energy production
Key Terms to Review (33)
Aldolase: Aldolase is a class of enzymes that catalyze the reversible aldol addition reaction, which is a key step in both the catabolism and anabolism of carbohydrates and lipids. This enzyme plays a crucial role in the glycolytic pathway, gluconeogenesis, and the breakdown of triacylglycerols, making it a central player in cellular energy metabolism.
Biotin: Biotin, also known as vitamin B7 or vitamin H, is an essential nutrient that plays a crucial role in the biosynthesis of fatty acids and carbohydrates. It is a cofactor for several key enzymes involved in these metabolic processes, making it an important consideration in the context of 29.4 Biosynthesis of Fatty Acids and 29.8 Carbohydrate Biosynthesis: Gluconeogenesis.
Carbon Flux: Carbon flux refers to the movement and exchange of carbon between different pools or reservoirs in the environment, such as the atmosphere, oceans, and terrestrial ecosystems. It is a crucial concept in understanding the global carbon cycle and the balance of carbon in various ecosystems.
Cortisol: Cortisol is a glucocorticoid hormone produced by the adrenal glands that plays a crucial role in the body's stress response and various metabolic processes, including carbohydrate, protein, and lipid metabolism.
Energy Metabolism: Energy metabolism refers to the set of chemical reactions and processes within the body that convert the energy stored in food molecules into forms that can be used to power cellular functions. It is the foundation for all life-sustaining activities, from powering muscle contractions to supporting brain activity.
Enolase: Enolase is a critical enzyme involved in the gluconeogenesis pathway, catalyzing the conversion of 2-phosphoglycerate to phosphoenolpyruvate, a key intermediate in the production of glucose from non-carbohydrate precursors.
Fructose-1,6-bisphosphatase: Fructose-1,6-bisphosphatase is a key enzyme in the gluconeogenesis pathway that catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate, an important step in the regulation of blood glucose levels.
Fructose-1,6-bisphosphate: Fructose-1,6-bisphosphate is a key intermediate in several important metabolic pathways, including the catabolism of triacylglycerols, the catabolism of carbohydrates through glycolysis, and the biosynthesis of carbohydrates via gluconeogenesis. It is an essential molecule that links these diverse metabolic processes together.
Glucagon: Glucagon is a hormone produced by the pancreas that plays a crucial role in regulating blood glucose levels. It is the counterpart to insulin, working to increase blood sugar when levels drop too low.
Glucogenic Amino Acids: Glucogenic amino acids are a group of amino acids that can be converted into glucose through the process of gluconeogenesis. These amino acids serve as precursors for the synthesis of glucose, which is the body's primary source of energy.
Gluconeogenesis: Gluconeogenesis is the metabolic process by which the body synthesizes glucose from non-carbohydrate precursors, such as amino acids, lactate, and glycerol. It is an important pathway that helps maintain blood glucose levels, especially during periods of fasting or starvation when glucose availability is limited.
Glucose Homeostasis: Glucose homeostasis is the process by which the body maintains a stable and optimal level of glucose in the blood, ensuring that cells have a consistent supply of this essential fuel. It is a critical aspect of carbohydrate metabolism and is closely linked to the topics of 29.8 Carbohydrate Biosynthesis: Gluconeogenesis.
Glucose-6-phosphatase: Glucose-6-phosphatase is an enzyme that catalyzes the final step in gluconeogenesis, the process of synthesizing glucose from non-carbohydrate precursors. It plays a crucial role in regulating blood glucose levels and maintaining glucose homeostasis in the body.
Glyceraldehyde-3-Phosphate Dehydrogenase: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key enzyme involved in the glycolytic pathway, catalyzing the oxidation and phosphorylation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate. It plays a crucial role in both the processes of biological reductions and carbohydrate biosynthesis through gluconeogenesis.
Glycerol: Glycerol, also known as glycerin, is a simple sugar alcohol that plays a crucial role in various biochemical processes related to fats, oils, and energy metabolism. This three-carbon compound is a key component in the structure of triacylglycerols, the primary storage form of lipids in the body, and is also involved in the production and utilization of energy through its participation in metabolic pathways.
Glycolysis: Glycolysis is the metabolic pathway that converts glucose, a six-carbon sugar, into two molecules of pyruvate, a three-carbon compound. This process is the first step in the catabolism of carbohydrates and is a fundamental part of cellular respiration, providing energy in the form of ATP to the cell.
GTP: GTP, or guanosine triphosphate, is a high-energy nucleotide that serves as a crucial energy currency in various cellular processes. It is closely related to the more well-known ATP (adenosine triphosphate) and plays a central role in several key metabolic pathways, including biological substitution reactions, the citric acid cycle, and carbohydrate biosynthesis via gluconeogenesis.
Hexokinase: Hexokinase is a crucial enzyme involved in the initial step of glycolysis, the metabolic pathway that breaks down glucose to generate energy in the form of ATP. It catalyzes the phosphorylation of glucose to glucose-6-phosphate, which is the first committed step in glucose metabolism.
Insulin: Insulin is a hormone produced by the pancreas that regulates blood sugar levels by facilitating the uptake and utilization of glucose by cells. It is a critical component in the metabolic processes of protein structure, DNA sequencing, fatty acid biosynthesis, and carbohydrate metabolism through gluconeogenesis.
Kidney Cortex: The kidney cortex is the outer layer of the kidney, surrounding the inner medulla. It is the site of the renal corpuscles, which are the functional units of the kidney responsible for the initial filtration of blood to form urine.
Lactate: Lactate is a chemical compound produced in the body during the process of anaerobic glycolysis, where glucose is broken down to generate energy without the use of oxygen. It plays a crucial role in the context of carbohydrate biosynthesis and the gluconeogenesis pathway.
Liver: The liver is a vital organ that plays a central role in carbohydrate metabolism, particularly in the process of gluconeogenesis. It is responsible for a wide range of essential functions, including the regulation of blood sugar levels, the production of bile for digestion, and the detoxification of various substances in the body.
Malate Dehydrogenase: Malate dehydrogenase is a crucial enzyme involved in the citric acid cycle, as well as in the process of gluconeogenesis. It catalyzes the reversible oxidation of malate to oxaloacetate, playing a central role in cellular energy production and carbohydrate metabolism.
Oxaloacetate: Oxaloacetate is a key intermediate in several important metabolic pathways, including the citric acid cycle, gluconeogenesis, and the regulation of enzyme activity through citrate synthase. As a 4-carbon dicarboxylic acid, oxaloacetate plays a central role in energy production and biosynthesis within the cell.
PEP Carboxykinase: PEP carboxykinase is a key enzyme involved in the process of gluconeogenesis, which is the metabolic pathway that produces glucose from non-carbohydrate precursors. It catalyzes the conversion of oxaloacetate to phosphoenolpyruvate (PEP), a critical step in the gluconeogenic pathway.
Phosphoenolpyruvate: Phosphoenolpyruvate (PEP) is a key intermediate in the metabolic pathways of glycolysis and gluconeogenesis. It is a high-energy phosphate compound that serves as a critical link between these two important carbohydrate-related processes in the body.
Phosphofructokinase-1: Phosphofructokinase-1 (PFK-1) is a crucial regulatory enzyme in the glycolytic pathway, responsible for catalyzing the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate. This irreversible, rate-limiting step is a key control point in carbohydrate metabolism, linking it to the processes of gluconeogenesis and glycolysis.
Phosphoglycerate Kinase: Phosphoglycerate kinase is a key enzyme involved in the glycolytic pathway, catalyzing the transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP, producing 3-phosphoglycerate and ATP. It plays a crucial role in the process of gluconeogenesis, the metabolic pathway that synthesizes glucose from non-carbohydrate precursors.
Phosphoglycerate Mutase: Phosphoglycerate mutase is an enzyme that catalyzes the interconversion of 3-phosphoglycerate (3-PG) and 2-phosphoglycerate (2-PG) in the glycolytic pathway and gluconeogenesis. It plays a crucial role in regulating the flow of carbon through these central metabolic processes.
Phosphohexose Isomerase: Phosphohexose isomerase, also known as glucose-6-phosphate isomerase, is a key enzyme involved in carbohydrate metabolism. It catalyzes the reversible isomerization of glucose-6-phosphate to fructose-6-phosphate, which is a crucial step in both glycolysis and gluconeogenesis.
Pyruvate: Pyruvate is a key intermediate molecule in cellular metabolism, serving as a central hub that connects various metabolic pathways. It is the final product of glycolysis, the process of breaking down glucose to generate ATP, and plays a crucial role in energy production, biosynthesis, and other essential metabolic processes within the body.
Pyruvate Carboxylase: Pyruvate carboxylase is a crucial enzyme that catalyzes the addition of a carboxyl group (CO2) to pyruvate, converting it into oxaloacetate. This reaction is a key step in the process of gluconeogenesis, the metabolic pathway that allows the body to synthesize glucose from non-carbohydrate precursors.
Pyruvate Kinase: Pyruvate kinase is a critical enzyme in the glycolytic pathway that catalyzes the final step of glycolysis, converting phosphoenolpyruvate (PEP) to pyruvate while generating ATP. This enzyme plays a crucial role in both the catabolism of carbohydrates through glycolysis and the biosynthesis of carbohydrates via gluconeogenesis.