Glycolysis and Krebs cycle

Glycolysis is the process in which glucose is broken down to produce energy. It produces two molecules of pyruvate, ATP, NADH and water. The process takes place in the cytosol of the cell cytoplasm, in the presence or absence of oxygen. Glycolysis is the primary step of cellular respiration. In the absence of oxygen, the cells take small amounts of ATP through the process of fermentation. This metabolic pathway was discovered by three German biochemists- Gustav Embden, Otto Meyerhof, and Jakub Karol Parnas in the early 19th century and are known as the EMP pathway (Embden–Meyerhof–Parnas).

Glycolysis stages:

Step 1: 

A phosphate group is added to glucose in the cell cytoplasm, by the action of enzyme hexokinase.

In this, a phosphate group is transferred from ATP to glucose forming glucose,6-phosphate.

Step 2: Glucose-6-phosphate is isomerized into fructose,6-phosphate by the enzyme phosphoglucomutase.

Step 3: The other ATP molecule transfers a phosphate group to fructose 6-phosphate and converts it into fructose 1,6-bisphosphate by the action of enzyme phosphofructokinase.

Step 4: The enzyme aldolase converts fructose 1,6-bisphosphate into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate, which are isomers of each other.

Step 5: Triose-phosphate isomerase converts dihydroxyacetone phosphate into glyceraldehyde 3-phosphate which is the substrate in the successive step of glycolysis.

Step 6: This step undergoes two reactions:

The enzyme glyceraldehyde 3-phosphate dehydrogenase transfers 1 hydrogen molecule from glyceraldehyde phosphate to nicotinamide adenine dinucleotide to form NADH + H+.

Glyceraldehyde 3-phosphate dehydrogenase adds a phosphate to the oxidized glyceraldehyde phosphate to form 1,3-bisphosphoglycerate.

Step 7: Phosphate is transferred from 1,3-bisphosphoglycerate to ADP to form ATP with the help of phosphoglycerokinase. Thus two molecules of phosphoglycerate and ATP are obtained at the end of this reaction.

Step8: The phosphate of both the phosphoglycerate molecules is relocated from the third to the second carbon to yield two molecules of 2-phosphoglycerate by the enzyme phosphoglyceromutase.

Step 9: The enzyme enolase removes a water molecule from 2-phosphoglycerate to form phosphoenolpyruvate.

Step 10: A phosphate from phosphoenolpyruvate is transferred to ADP to form pyruvate and ATP by the action of pyruvate kinase. Two molecules of pyruvate and ATP are obtained as the end products.

The Krebs cycle or Citric acid cycle is a series of enzyme catalysed reactions occurring in the mitochondrial matrix, where acetyl-CoA is oxidised to form carbon dioxide and coenzymes are reduced, which generate ATP in the electron transport chain.

Krebs cycle was named after Hans Krebs, who postulated the detailed cycle. He was awarded the Nobel prize in 1953 for his contribution.

It is a series of eight-step processes, where the acetyl group of acetyl-CoA is oxidised to form two molecules of CO2 and in the process, one ATP is produced. Reduced high energy compounds, NADH and FADH2 are also produced.

Two molecules of acetyl-CoA are produced from each glucose molecule so two turns of the Krebs cycle are required which yields four CO2, six NADH, two FADH2 and two ATPs.

Krebs cycle steps:

It is an eight-step process. The Krebs cycle takes place in the matrix of mitochondria under aerobic conditions.

Step 1: The first step is the condensation of acetyl CoA with 4-carbon compound oxaloacetate to form 6C citrate, coenzyme A is released. The reaction is catalysed by citrate synthase.

Step 2: Citrate is converted to its isomer, isocitrate. The enzyme aconitase catalyses this reaction.

Step 3: Isocitrate undergoes dehydrogenation and decarboxylation to form 5C 𝝰-ketoglutarate. A molecular form of CO2 is released. Isocitrate dehydrogenase catalyses the reaction. It is an NAD+ dependent enzyme. NAD+ is converted to NADH.

Step 4: 𝝰-ketoglutarate undergoes oxidative decarboxylation to form succinyl CoA, a 4C compound. The reaction is catalyzed by 𝝰-ketoglutarate dehydrogenase enzyme complex. One molecule of CO2 is released and NAD+ is converted to NADH.

Step 5: Succinyl CoA forms succinate. The enzyme succinyl CoA synthetase catalyses the reaction. This is coupled with substrate-level phosphorylation of GDP to get GTP. GTP transfers its phosphate to ADP forming ATP.

Step 6: Succinate is oxidised by the enzyme succinate dehydrogenase to fumarate. In the process, FAD is converted to FADH2.

Step 7: Fumarate gets converted to malate by the addition of one H2O. The enzyme catalysing this reaction is fumarase.

Step 8: Malate is dehydrogenated to form oxaloacetate, which combines with another molecule of acetyl CoA and starts the new cycle. Hydrogens removed, get transferred to NAD+ forming NADH. Malate dehydrogenase catalyses the reaction.

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