Glycolysis also name as Embden-Meyerhof pathway, is a process in which one mole of glucose is partially oxidized into the two moles of pyruvate in a series of enzyme-catalyzed reactions. Glycolysis occur in the cytosol of all cells. It is a unique pathway that occurs in both aerobic as well as anaerobic conditions and does not involve molecular oxygen i.e. oxygen independent.
Step 1 (Phosphorylation) :
Glucose is phosphorylated by ATP to form glucose-6-phosphate. The negative charge of the phosphate prevents the passage of the glucose-6-phosphate through the plasma membrane, trapping glucose inside the cell. This irreversible reaction is catalyzed by Hexokinase. Hexokinase is present in all cells of all organisms. It requires divalent metals such as Mg2+ or Mn2+ for activity. Hexokinase are isozymes.
Step 2 (Isomerization) :
A reversible rearrangement of chemical structure moves the carbonyl oxygen from carbon 1 to carbon 2, forming a ketose from an aldose sugar. Thus, the isomerization of glucose-6-phosphate to fructose-6-phosphate is a conversion of an aldose into ketose. This step is catalyzed by the enzyme Phosphoglucoisomerase.
Step 3 (Phosphorylation) :
Fructose-6-phosphate is phosphorylated by ATP to fructose 1,6 bisphosphate. The prefix bis- in bisphosphate means that two separate monosaccharide groups are present, whereas the prefix di- means that two phosphate groups are present and are connected by an anhydride bond. This irreversible reaction is catalyzed by an allosteric enzyme Phosphofructokinase-1 (PFK-1).
Step 4 (Cleavage) :
The fructose 1,6 bisphosphate is cleaved to produce two three-carbon molecules- Glyceraldehyde 3 phosphate (G3P) and dihydroxyacetone phosphate (DHAP). This reaction is catalyzed by enzyme Aldose.
Step 5 (Isomerization) :
Only one of two triose phosphate formed by aldose-glyceraldehyde 3-phosphate can be directly degraded in the subsequent reaction steps of glycolysis. However, the other product, dihydroxyacetone phosphate, is rapidly and reversible converted into glyceraldehyde 3 phosphate by the enzyme Triose phosphate isomerase.
Step 6 :
The two molecules of Glyceraldehyde 3 phosphate are oxidized. Enzyme glyceraldehyde 3 phosphate dehydrogenase catalyzes the conversion G3P into 1,3-bisphoshoglycerte(1,3-BPG). The reaction occurs in two steps : First the oxidation of the aldehyde to a carboxylic acid by NAD+ and Second the phosphorylation of carbolic acid by inorganic phosphate (not by ATP). Iodoacetate is potent in inhibitor of glyceraldehyde 3 phosphate dehydrogenase because it forms a covalent derivative of the essential -SH group of the enzyme active site, rendering it inactivate.
Step 7 :
In this step, high-energy phosphate group is transferred from 1,3-bisphoglycerate to ADP. This step is catalyzed by enzyme phosphoglycerate kinase. The formation of ATP is referred to as substrate-level phosphorylation because the phosphate donor, 1,3-bisphosphoglycerate, is a substrate with high phosphoryl-transfer potential.
Formation of ATP from ADP by direct transfer of phosphoryl group from a 'high-energy' compound is termed as substrate-level phosphorylation. Erythrocytes possess a unique glycolytic bypass for the production of 2,3-phosphoglycerate (2,3-BPG), the Rapoport-Luebering shunt. The shunt bypass the phosphoglycerate kinase step and accounts for the synthesis and regulation of 2,3-BPG levels that decrease hemoglobin's affinity for oxygen.
Step 8 :
The remaining phosphate ester linkage in 3-phosphoglycerate, which has a relatively low free energy of hydrolysis, is moved from carbon 3 to carbon 2 to form 2-phosphoglycerate.
Step 9 :
The removal of water from 2-phosphoglycerate creates a high-energy enol phosphate linkage. The enzyme catalyzing this step, Enolase, is inhibition by fluoride.
Step 10 :
The transfer of the high-energy phosphate group that was generated in step 9 to ADP forms ATP. This last step in glycolysis is the irreversible transfer of the phosphoryl group from phosphoenol pyruvate to ADP is catalyzed by Pyruvate kinase. Pyruvate kinase requires K+ and either Mg2+ or Mn2+ .
Net Reaction : Glucose + 2NAD+ + 2ADP + 2HPO3 -2 ______ 2 Pyruvate + 2NADH + 2ATP + 2H2O
Regulation of Glycolysis
The rate at which the glycolytic pathway operates is controlled primarily by allosteric regulation of three enzymes; Hexokinase, Phosphofructokinase-1 and Pyruvate kinase. The reaction catalyzed by three enzymes are irreversible. Allosteric effector glucose-6-phosphate inhibits the hexokinases. A high AMP concentration activates phosphofructokinase-1 and pyruvate kinase. In contrast, a high AMP concentration inhibits both enzymes. Citrate and acetyl-CoA, which indicate that alternative energy source are available, inhibit phosphofructokinase-1 and pyruvate kinase, respectively. Finally, fructose 2,6-bisphosphate stimulates glycolysis by activating phoshofructokinase-1 and fructos-1,6-bisphosphate activates pyruvate kinase.
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