What is gluconeogenesis? Definition, Pathway and Regulation - Biology Readers (2023)

Gluconeogenesis occurs in the opposite way to glycolysis, which producesGlucosethrough precursors such as pyruvate, lactate, glucogenic amino acids. is sometimes calledNeoglucogenesis. Is it omnipresent orUniversal-Metabolic pathway found in humans, animals, plants, fungi, and other living organisms.

Gluconeogenesis has only three irreversible steps versus the glycolytic pathway, while the other seven steps are common. containsfour reactionswithout going through the three irreversible reactions of glycolysis.

We could understand the meaning of gluconeogenesis by dividing the term into gluco, neo and genesis. It is now very easy to remember the importance of gluconeogenesis, in whichGlucosemeans glucose,neomeans new andGenesisindicates a summary. Therefore, do not get confused by terms such as glycolysis, glycogenesis, glycogenolysis.

In this context, we will address the definition, place of occurrence, importance and stages of the gluconeogenesis pathway. Furthermore, the substrates that initiate the gluconeogenesis pathway along with the regulation of gluconeogenesis are explained.

Contents: Gluconeogenesis

1. Definition
2. Where is the state of gluconeogenesis?
3. gluconeogenesis pathway
4. Substrate
5. Meaning
6. Regulation of Gluconogenesis

Definition of Gluconogenesis

GNG is an acronym for the term gluconeogenesis. Refers to the metabolic pathway that synthesizes newGlucosemolecules of theglucose-free substratesas lactate and TCA intermediates. Gluconeogenesis is sometimes also called "Endogenous of Glukoseweg' because it requires energy input.

The small precursor molecules combine to form a high-energy product such as glucose. Gluconeogenesis is an important cycle that produces glucose, known as "key metabolite” to carry out all catabolic processes and sustain life.

Where is the state of gluconeogenesis?

The process of neoglucogenesis takes place in the liver, renal cortex and enterocytes of the small intestine. Most steps of gluconeogenesis occur internally.citosolthan in mitochondria.

gluconeogenesis pathway

Gluconeogenesis differs from glycolysis in having three irreversible reactions mediated by three different enzymes.

Step 1: Conversion of pyruvate to phosphoenolpyruvate

It is the first reaction to circumvent an irreversible reaction mediated by glycolysis.pyruvatequinase. The conversion of pyruvate to phosphoenolpyruvate involves two sequences of steps:

Carboxylation of pyruvate to oxaloacetate

Pyruvate carboxylase mediates the conversion of pyruvate to oxaloacetate through the addition of a carbon dioxide molecule. An enzyme (pyruvate carboxylase) was first discovered in the 1960s by a scientist namedMerton absoluto.

Pyruvatcarboxylase is amitochondrial enzymeallows pyruvate present in the cytosol to enter the mitochondrial matrix through an association ofMPC-1YMPC-2complexes.

The carboxylation of pyruvate to oxaloacetate requires a high energy input.atpmolecule and the presence of Mg²⁺and manganese²⁺ions The carboxylation of pyruvate leads to the formation of oxaloacetate and an ADP.

Decarboxylation of oxaloacetate to phosphoenolpyruvate

The transport of oxaloacetate from the mitochondria to the cytosol does not involve any transporter complexes ortransporter. It only happens throughreductionof oxaloacetate inmalateAbovemitochondrial malate dehydrogenase.

Malate then moves across the inner mitochondrial membrane via the malate-aspartate shuttle and the malate-α-ketoglutarate transporter. Malate is reoxidized in the cytosoloxaloacetatoby an enzyme (cytosolic malate dehydrogenase).

Phosphoenolpyruvate carboxycinasaconverts oxaloacetate to phosphoenolpyruvate by eliminationcarbon dioxide. It is ait's still difficultequally present in mitochondria and cytosol.

The decarboxylation of oxaloacetate to phosphoenolpyruvate requires a lot of energy.atpmolecule and the presence ofmilligrams²⁺YMinnesota²⁺ions. This reaction isreversibleunder normal cellular conditions.

Step 2: dephosphorylation of fructose-1,6-bisphosphate into fructose-6-phosphate

It is a side reaction that circumvents an irreversible enzyme-mediated glycolysis reaction.Phosphofructokinase. in gluconeogenesisFructose-1,6-phosphataseThe enzyme mediates the dephosphorylation of fructose-1,6-bisphosphate to fructose-6-phosphate and requiresmilligrams²⁺ions An enzyme (Fructose-1,6-phosphatase) causes hydrolysis ofC-1-Phosphatein the fructose-1,6-bisphosphate molecule, without releasing ATP.

Step 3: dephosphorylation of glucose-6-phosphate into glucose

It is a third step that bypasses an irreversible reaction of enzyme-catalyzed glycolysis.Hexoquinasa. On the other hand, glucose-6-phosphatase promotes this reaction in a gluconeogenesis cycle and dephosphorylates glucose-6-phosphate into glucose.

Glucose-6-phosphatase is a protein complex located in the membrane of the endoplasmic reticulum. consists of aactive catalyticPropertyit is aTraubComplex.

The active catalytic site mediates the release of glucose into the lumen of the endoplasmic reticulum (not the cytosol) by the transporter complex.Glucose-6-Fosfato-TranslokaseoT1“. Glucose-6-phosphatase is dependent onmilligrams²⁺ionswhich catalyzes thelast step.

The glucose molecule formed after the dephosphorylation of glucose-6-phosphate is transported to the cytoplasm by glucose transporters.Endoplasmatisches Retikulum.

Substrate

All intermediates of glycolysis and the tricarboxylic acid cycle provide a substrate for gluconeogenesis. Contains substrates such as glycerol, lactate, glucogenic amino acid, etc.

Glycerin

It is a product made fromtriglycerides Hydrolysisin adipose tissue and through the blood to the liver. Glycerol is an intermediate substrate that produces glucose exclusively in the cytosol. Enter the cycle through the two consecutive steps:

Glycerol kinase is an enzyme found in bothLiverYRinswhich performs the phosphorylation of glycerol to glycerol-3-phosphate usingatp.

The oxidation of glycerol phosphate to dihydroxyacetone phosphate occurs because theSHEreduce oneNADH. Dihydroxyacetone is an intermediate in the glycolytic pathway.

lactate

It is a product formed as a result ofanaerobic glycolysisin skeletal muscle and erythrocytes. Lactate is transported in the blood from the muscles to the liver. turns back topyruvatein the liver and then takes over the production ofGlucosethrough gluconeogenesis.

glucogenic amino acids

They are obtained from the hydrolysis oftissue proteins. Glucogenic acids like α-ketoglutaramate, succinyl Co-A, fumarate, oxaloacetate and fumarate are the only precursors that can produce glucose. There are two entry points viz.pyruvateYoxaloacetato,through which glucogenic amino acids can enter the gluconeogenesis cycle.

Meaning

1. The gluconeogenesis cycle plays a crucial role inblood sugar homeostasisduring famine.
2. The product of gluconeogenesis, i.e. glucose, meets the requirementsenergy demandmany cells and tissues, such as erythrocytes, neurons, skeletal muscle, renal medulla, testes, embryonic tissue, etc.
3. The gluconeogenesis cycleclean metabolitesaccumulated in the blood, such as lactate (made from muscle and red blood cells) and glycerol (made from adipose tissue).

Regulation of gluconeogenesis

The regulation of gluconeogenesis includes the following factors:

Acetyl-CoA

It's a kind ofmutual regulation, which regulates the conversion of pyruvate to PEP. Acetyl-Co-A accumulates in the liver as a result of excessive lipolysis in adipose tissue. When the concentration of Acetyl-Co-A is higher, it inhibits the glycolytic enzymephosphate dehydrogenaseactivates and stimulates the activity of pyruvate carboxylase.

Therefore, high level of acetyl-Co-A affects the gluconeogenesis cycle. You can adjust the path either positively or negatively.

• positive regulation: Acetyl Co-A promotes the enzymatic activity of pyruvate carboxylase, which in turn produces more oxaloacetate and glucose as an end product.
• negative regulation: Acetyl-Co-A inhibits the enzymatic activity of pyruvate dehydrogenase, which converts pyruvate carboxylase to acetyl-Co-A.

glucagon

It is a kind of hormonal regulation secreted by thecells αof the pancreatic islets when the blood sugar level in a body starts to drop.

Glucagon regulates the conversion of fructose-1,6-bisphosphate to fructose-6-phosphate or promotes the process of gluconeogenesis through the following two mechanisms:

• glucagon-mediatedcyclic AMPwhich can convert pyruvate kinase into an inactive form, resulting in the conversion of PEP to pyruvate. Finally, it redirects the circuit to glucose synthesis.
• Second, glucagon reduces the concentration ofFructose 2,6-phosphatewhich inhibits the enzymatic activity of phosphofructokinase and activates fructose-1,6-bisphosphate to promote glucose synthesis.

glucogenic amino acids

It's a kind ofSubstrate level regulation, which regulates the conversion of glucose-6-phosphate to glucose. Substrates such as glycogenic acid affect the neoglucogenesis process at the time of reduced insulin levels. Meanwhile, as insulin concentration decreases, amino acids are metabolized by muscle protein.Gluconoogenese.