Glyconeogenesis

\( \newcommand\) • • • • • • Introduction The need for energy is important to sustain life. Organisms have evolved ways of producing substrates required for the catabolic reactions necessary to sustain life when desired substrates are unavailable. The main source of energy for eukaryotes is glucose. When glucose is unavailable, organisms are capable of metabolizing glucose from other non-carbohydrate precursors. The process that coverts pyruvate into glucose is called gluconeogenesis. GluconeogenesisIs Not a Reversal of Glycolysis In glycolysis, glucose is converted into pyruvate; in gluconeogenesis, pyruvate is converted into glucose. However, gluconeogenesisis not a reversal of glycolysis. Several reactions must differ because the equilibrium of glycolysis lies far on the side of pyruvate formation. The actual Δ -1(-84 kJ mol -1) under typical cellular conditions. Most of the decrease in free energy in glycolysis takes place in the three essentially irreversible steps catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase. In gluconeogenesis, the following new steps bypass these virtually irreversible reactions of glycolysis: 1. Phosphoenolpyruvate is formed from pyruvate by way of oxaloacetatethrough the action of pyruvate carboxylase and phosphoenolpyruvate carboxykinase. 2.Fructose 6-phosphate is formed from fructose 1,6-bisphosphate by hydrolysis of the phosphate ester at carbon 1. Fructose 1,6-bisphosphatase catalyzes this exergonic hydrolysis. 3. Glucose...

https://bio.libretexts.org/@app/auth/3/login?returnto=https%3A%2F%2Fbio.libretexts.org%2FBookshelves%2FBiochemistry%2FFundamentals_of_Biochemistry_(Jakubowski_and_Flatt)%2F02%253A_Unit_II-_Bioenergetics_and_Metabolism%2F13%253A_Glycolysis_Gluconeogenesis_and_the_Pentose_Phosphate_Pathway%2F13.03%253A_Gluconeogenesis Expand/collapse global hierarchy • Home • Bookshelves • Biochemistry • Fundamentals of Biochemistry (Jakubowski and Flatt) • Fundamentals of Biochemistry Vol. II - Bioenergetics and Metabolism • 13: Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway • 13.3: Gluconeogenesis Expand/collapse global location \( \newcommand\) • • • • • Search Fundamentals of Biochemistry Introduction Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids. It is one of the two main mechanisms humans and many other animals use to keep blood glucose levels from dropping too low (hypoglycemia). The other means of maintaining blood glucose levels is through the degradation of glycogen (glycogenolysis). Gluconeogenesis is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In animals, gluconeogenesis takes place mainly in the liver and, to a lesser extent, in the cortex of the kidneys. This process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise and is highly endergonic. For ex...

\( \newcommand\). The glyoxylate cycle. • Once the macromolecules have been broken down to acetyl-CoA, they enter the glyoxysome and combine with oxaloacetate to make citrate. This is catalyzed by citrate synthase just as in the mitochondrial TCA cycle. The next reaction also uses a familiar enzyme: aconitase catalyzes the conversion of citrate to isocitrate. However, the aconitase is a cytosolic enzyme, so the citrate is transported out of the glyoxysome and then the isocitrate transported back in. • At this point, the glyoxysomal-specific enzyme, isocitrate lyase, hydrolyzes isocitrate to yield succinate and glyoxylate. The succinate is transported to the mitochondrion, where TCA cycle enzymes convert it to fumarate and then malate, which is transported out to the cytosol. In the cytosol, the malate is converted to oxaloactetate through malate dehydrogenase, and gluconeogenesis can proceed. • The glyoxylate is acted upon by another glyoxysomal enzyme, malate synthase, which adds it to acetyl-CoA to form malate. • The final step of the glyoxysomal portion of the glyoxylate cycle is oxidation of the malate to oxaloacetate by glyoxysomal malate dehydrogenase. So, to summarize, the pool of oxaloacetate within the glyoxysome is used and regenerated within the glyoxysome. Acetyl-CoA is converted to succinate within the glyoxysome, but then goes to the mitochondrion for conversion to malate, and finally the cytosol for conversion to a separate pool of oxaloacetate that is then ...

Gluconeogenesis occurs principally in the e.g., the synthesis of blood glucose from lactate in the liver is a particularly active process during recovery from intense muscular exertion. Although several of the reactions in the gluconeogenetic pathway are catalyzed by the same enzymes that catalyze the reverse sequence,

https://bio.libretexts.org/@app/auth/3/login?returnto=https%3A%2F%2Fbio.libretexts.org%2FBookshelves%2FBiochemistry%2FFundamentals_of_Biochemistry_(Jakubowski_and_Flatt)%2F02%253A_Unit_II-_Bioenergetics_and_Metabolism%2F13%253A_Glycolysis_Gluconeogenesis_and_the_Pentose_Phosphate_Pathway%2F13.03%253A_Gluconeogenesis Expand/collapse global hierarchy • Home • Bookshelves • Biochemistry • Fundamentals of Biochemistry (Jakubowski and Flatt) • Fundamentals of Biochemistry Vol. II - Bioenergetics and Metabolism • 13: Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway • 13.3: Gluconeogenesis Expand/collapse global location \( \newcommand\) • • • • • Search Fundamentals of Biochemistry Introduction Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids. It is one of the two main mechanisms humans and many other animals use to keep blood glucose levels from dropping too low (hypoglycemia). The other means of maintaining blood glucose levels is through the degradation of glycogen (glycogenolysis). Gluconeogenesis is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In animals, gluconeogenesis takes place mainly in the liver and, to a lesser extent, in the cortex of the kidneys. This process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise and is highly endergonic. For ex...

\( \newcommand\). The glyoxylate cycle. • Once the macromolecules have been broken down to acetyl-CoA, they enter the glyoxysome and combine with oxaloacetate to make citrate. This is catalyzed by citrate synthase just as in the mitochondrial TCA cycle. The next reaction also uses a familiar enzyme: aconitase catalyzes the conversion of citrate to isocitrate. However, the aconitase is a cytosolic enzyme, so the citrate is transported out of the glyoxysome and then the isocitrate transported back in. • At this point, the glyoxysomal-specific enzyme, isocitrate lyase, hydrolyzes isocitrate to yield succinate and glyoxylate. The succinate is transported to the mitochondrion, where TCA cycle enzymes convert it to fumarate and then malate, which is transported out to the cytosol. In the cytosol, the malate is converted to oxaloactetate through malate dehydrogenase, and gluconeogenesis can proceed. • The glyoxylate is acted upon by another glyoxysomal enzyme, malate synthase, which adds it to acetyl-CoA to form malate. • The final step of the glyoxysomal portion of the glyoxylate cycle is oxidation of the malate to oxaloacetate by glyoxysomal malate dehydrogenase. So, to summarize, the pool of oxaloacetate within the glyoxysome is used and regenerated within the glyoxysome. Acetyl-CoA is converted to succinate within the glyoxysome, but then goes to the mitochondrion for conversion to malate, and finally the cytosol for conversion to a separate pool of oxaloacetate that is then ...

Gluconeogenesis occurs principally in the e.g., the synthesis of blood glucose from lactate in the liver is a particularly active process during recovery from intense muscular exertion. Although several of the reactions in the gluconeogenetic pathway are catalyzed by the same enzymes that catalyze the reverse sequence,

\( \newcommand\) • • • • • • Introduction The need for energy is important to sustain life. Organisms have evolved ways of producing substrates required for the catabolic reactions necessary to sustain life when desired substrates are unavailable. The main source of energy for eukaryotes is glucose. When glucose is unavailable, organisms are capable of metabolizing glucose from other non-carbohydrate precursors. The process that coverts pyruvate into glucose is called gluconeogenesis. GluconeogenesisIs Not a Reversal of Glycolysis In glycolysis, glucose is converted into pyruvate; in gluconeogenesis, pyruvate is converted into glucose. However, gluconeogenesisis not a reversal of glycolysis. Several reactions must differ because the equilibrium of glycolysis lies far on the side of pyruvate formation. The actual Δ -1(-84 kJ mol -1) under typical cellular conditions. Most of the decrease in free energy in glycolysis takes place in the three essentially irreversible steps catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase. In gluconeogenesis, the following new steps bypass these virtually irreversible reactions of glycolysis: 1. Phosphoenolpyruvate is formed from pyruvate by way of oxaloacetatethrough the action of pyruvate carboxylase and phosphoenolpyruvate carboxykinase. 2.Fructose 6-phosphate is formed from fructose 1,6-bisphosphate by hydrolysis of the phosphate ester at carbon 1. Fructose 1,6-bisphosphatase catalyzes this exergonic hydrolysis. 3. Glucose...

\( \newcommand\). The glyoxylate cycle. • Once the macromolecules have been broken down to acetyl-CoA, they enter the glyoxysome and combine with oxaloacetate to make citrate. This is catalyzed by citrate synthase just as in the mitochondrial TCA cycle. The next reaction also uses a familiar enzyme: aconitase catalyzes the conversion of citrate to isocitrate. However, the aconitase is a cytosolic enzyme, so the citrate is transported out of the glyoxysome and then the isocitrate transported back in. • At this point, the glyoxysomal-specific enzyme, isocitrate lyase, hydrolyzes isocitrate to yield succinate and glyoxylate. The succinate is transported to the mitochondrion, where TCA cycle enzymes convert it to fumarate and then malate, which is transported out to the cytosol. In the cytosol, the malate is converted to oxaloactetate through malate dehydrogenase, and gluconeogenesis can proceed. • The glyoxylate is acted upon by another glyoxysomal enzyme, malate synthase, which adds it to acetyl-CoA to form malate. • The final step of the glyoxysomal portion of the glyoxylate cycle is oxidation of the malate to oxaloacetate by glyoxysomal malate dehydrogenase. So, to summarize, the pool of oxaloacetate within the glyoxysome is used and regenerated within the glyoxysome. Acetyl-CoA is converted to succinate within the glyoxysome, but then goes to the mitochondrion for conversion to malate, and finally the cytosol for conversion to a separate pool of oxaloacetate that is then ...

https://bio.libretexts.org/@app/auth/3/login?returnto=https%3A%2F%2Fbio.libretexts.org%2FBookshelves%2FBiochemistry%2FFundamentals_of_Biochemistry_(Jakubowski_and_Flatt)%2F02%253A_Unit_II-_Bioenergetics_and_Metabolism%2F13%253A_Glycolysis_Gluconeogenesis_and_the_Pentose_Phosphate_Pathway%2F13.03%253A_Gluconeogenesis Expand/collapse global hierarchy • Home • Bookshelves • Biochemistry • Fundamentals of Biochemistry (Jakubowski and Flatt) • Fundamentals of Biochemistry Vol. II - Bioenergetics and Metabolism • 13: Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway • 13.3: Gluconeogenesis Expand/collapse global location \( \newcommand\) • • • • • Search Fundamentals of Biochemistry Introduction Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids. It is one of the two main mechanisms humans and many other animals use to keep blood glucose levels from dropping too low (hypoglycemia). The other means of maintaining blood glucose levels is through the degradation of glycogen (glycogenolysis). Gluconeogenesis is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In animals, gluconeogenesis takes place mainly in the liver and, to a lesser extent, in the cortex of the kidneys. This process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise and is highly endergonic. For ex...