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Glycolysis Steps with Structures

    In this glycolysis steps with structures post we have briefly explained about history, definition, steps of glycolytic pathway, energy yield from glycolysis mechanism, and regulation.

    Glycolysis Steps with Structures

    The complete glycolytic pathway was elucidated by 1940, largely through the pioneering contributions of Gustav Embden, Otto Meyerhof, Carl Neuberg, Jacob Parnas, Otto Warburg, Gerty Cori, and Carl Cori. Glycolysis mechanism is also known as the Embden-Meyerhof pathway.

    Definition

    In aerobic conditions, glucose is split into two 3-carbon pyruvate molecules; under anaerobic conditions, glucose is broken into lactate, along with the generation of a small amount of energy. Glycolysis mechanism comes from the Greek words glykys, which means sweet, and lysis, which means splitting.

    Glycolysis Mechanism

    It is the only pathway that runs through all of the body’s cells. In erythrocytes, glycolysis mechanism is the only source of energy. When muscle tissue is deprived of oxygen during hard exercise, anaerobic glycolysis mechanism becomes the primary source of energy for muscles.

    The glycolytic process produces carbon skeletons for non-essential amino acid synthesis as well as the glycerol component of fat. The glycolytic pathway’s majority of processes are reversible, and they’re also utilised in gluconeogenesis.

    Glucose Absorption by Cells

    Glucose transporter-4 (GluT4) is a protein that transfers glucose from the extracellular fluid to muscle and adipocyte cells. Insulin regulates the activity of this translocase. Insulin insufficiency in diabetes mellitus prevents glucose from entering peripheral cells.

    Glycolysis Steps with Structures

    Step - 1

    Phosphorylation of glucose results in glucose-6-phosphate. Hexokinase (HK) is the enzyme that splits ATP into ADP and adds the Pi to the glucose. The forward process uses the energy provided by the hydrolysis of ATP.

    Hexokinase catalyses an irreversible regulatory step in glycolysis mechanism. However, another enzyme, glucose-6-phosphatase, prevents this irreversibility. Glucose is trapped within cells due to phosphorylation. Glucose-6-phosphate is locked within the cell after being phosphorylated and must be metabolised.

    Step - 2

    Phosphohexose isomerase converts glucose-6-phosphate to fructose-6-phosphate. This is easily undoable.

    Step - 3

    The preliminary phase is comprised of phases 1, 2, and 3. Fructose-6-phosphate is converted to fructose1,6-bisphosphate via phosphorylation. Phosphofructokinase is the enzyme in question.

    PFK is a regulating enzyme that is allosteric and inducible. It is a critical enzyme in this pathway. This is another activation process, with the energy coming from the hydrolysis of yet another ATP molecule.

    In glycolysis mechanism, this irreversible phase is the rate limiting reaction. Fructose-1,6-bisphosphatase, on the other hand, bypasses this step during gluconeogenesis.

    Step - 4

    The six-carbon fructose-1,6-bisphosphate is broken down into two three-carbon units: one glyceraldehyde-3-phosphate molecule and another dihydroxy acetone phosphate (DHAP) molecule. The enzyme is termed aldolase because the reverse reaction is an aldol condensation. This reaction can be reversed.

    The enzyme phosphotriose isomerase converts dihydroxy acetone phosphate to glyceraldehyde-3-phosphate. As a result, glucose is now broken down into two molecules of glyceraldehyde-3-phosphate. The splitting phase is comprised of stages 4 and 4-A.

    Step - 5

    With the help of NAD+, glyceraldehyde-3-phosphate is dehydrogenated and simultaneously phosphorylated to 1, 3-bisphospho glycerate (1, 3-BPG). Glyceraldehyde-3-phosphate dehydrogenase is the enzyme. A high-energy bond is present in the product.

    Step - 6

    Bisphospho glycerate kinase traps the energy of 1,3-BPG in order to produce one ATP molecule. This is an example of substrate level phosphorylation, in which energy is trapped directly from the substrate, bypassing the intricate electron transport chain processes. It’s called oxidative phosphorylation when energy is captured by oxidation of reducing equivalents like NADH. Step 6 can be reversed.

    Step - 7

    By transferring the phosphate group from the third to the second carbon atom, 3-phospho glycerate is isomerized to 2-phospho glycerate. Phosphoglucomutase is the enzyme under issue. This is a simple reaction that can be reversed.

    Step - 8

    The enzyme enolase converts 2-phosphoglycerate to phosphoenol pyruvate. One molecule of water is eliminated. A phosphate bond with a high energy is formed. The reaction can be reversed.

    Enolase requires Mg++, and fluoride inhibits this enzyme irreversibly by withdrawing magnesium ions. As a result, fluoride will stop the entire glycolysis mechanism process.

    As a result, fluoride is added to blood when it is drawn for the purpose of determining blood sugar levels. If not, glucose is digested by blood cells, resulting in decreased blood glucose levels.

    Step - 9

    Pyruvate kinase dephosphorylates phosphoenol pyruvate (PEP) to pyruvate. PEP is first converted to an enol pyruvate transitory intermediate, which is then spontaneously isomerized into keto pyruvate, the stable form of pyruvate.

    During this process, one mole of ATP is produced. This is another example of phosphorylation at the substrate level.

    A major glycolytic enzyme is pyruvate kinase. This is a final step that cannot be reversed. However, two enzymes (pyruvate kinase and phosphoenol pyruvate carboxy kinase) and the hydrolysis of two ATP molecules can reverse the process in the body.

    Step - 10

    In the presence of K+ and Mg++ or Mn++ ions, the enzyme pyruvate kinase catalyses this reaction. This is also a substrate-level phosphorylation in which the phosphoryl group from PEP to ADP is transferred, resulting in ATP and Pyruvate. The product pyruvate first arrives in its enol form, which subsequently tautomerizes swiftly and non-enzymatically to its keto form in this substrate level phosphorylation.

    Energy Yield from Glycolysis

    When one molecule of glucose is transformed to two molecules of lactate under anaerobic (oxygen-deficient) conditions, a net yield of two molecules of ATP is produced.

    The two substrate-level phosphorylations (steps 6 and 9) produce 4 molecules of ATP. However, because steps 1 and 3 utilise 2 molecules of ATP, the net yield is just 2 ATP.

    Glucose + 2 Pi + 2 ADP —> 2 Lactate + 2 ATP

    When oxygen is plentiful, however, the two NADH molecules produced in the glyceraldehyde-3-phosphate dehydrogenase enzyme (step 5) can join the mitochondrial electron transport chain and complete the oxidation process.

    This process produces 2.5 x 2 = 5 ATPs since each NADH contributes 2.5 ATPs. When oxygen is available, the glycolysis mechanism cycle generates a net gain of 7 ATPs.

    As a result, the anaerobic and aerobic ATP yields from glycolysis mechanism differ. Later, pyruvate is oxidatively decarboxylated to acetyl CoA, which enters the citric acid cycle. A total of 32 ATPs are produced when glucose is completely oxidised via glycolysis and the citric acid cycle.

    Regulation of Glycolysis

    1. Glucokinase/Hexokinase

    These enzymes phosphorylate glucose, which is controlled by feedback inhibition (hexokinase by glucose-6-phosphate) and triggered by insulin (glucokinase is induced by insulin). Glucokinase, which is mostly found in the liver, has a high Km for glucose and a low affinity for it. As a result, glucokinase can only function when there is enough glucose available to store any surplus.

    Hexokinase with a low Km and a high affinity for glucose can phosphorylate glucose even at low concentrations, allowing glucose to reach the brain, heart, and skeletal muscle. Glucokinase can only function when there is a sufficient supply of glucose. When glucose is in short supply, glucose is made available to the brain and muscles.

    2. Phosphofructokinase (PFK)

    The most significant rate-limiting enzyme for the glycolysis mechanism process is phosphofructokinase (PFK) (step 3). The most important allosteric inhibitors are ATP and citrate. Allosteric activation is how AMP works.

    3. Fructose-2,6-bisphosphate

    The activity of phospho fructo kinase is increased by fructose-2,6-bisphosphate (F-2,6-BP). The action of an enzyme called PFK-2 converts fructose-6-phosphate to F-2, 6-BP.

    Fructose-2,6-bisphosphatase breaks down fructose-2,6-bisphosphate into fructose-6-phosphate. Both enzymes’ activity (PFK2 and fructose-2,6-bisphosphatase) are regulated in a reciprocal manner.

    When glucose is abundant, PFK-2 is dephosphorylated and activated, causing F2,6-BP concentration to rise, activating PFK. As a result, glycolysis mechanism is favoured.

    4. Pyruvate Kinase

    Pyruvate Kinase is a glycolysis mechanism regulating enzyme that catalyses an irreversible process. Glycolysis mechanism is inhibited when the cell has enough energy. Insulin stimulates it, whereas glucagon inhibits it. In the phosphorylated form, pyruvate kinase is inactive.

    Insulin promotes glycolysis mechanism by activating the three glycolytic enzymes mentioned above. Glucagon and glucocorticoids decrease glycolysis and enhance gluconeogenesis.

    Further Readings

    Reference