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 is a Part of Cellular Respiration
Cellular respiration is a catabolic reaction taking place in the cells. It is a biochemical process by which nutrients are broken down to release energy, which gets stored in the form of ATP and waste products are released. In aerobic respiration, oxygen is required.
Cellular respiration is a four-stage process. In the process, glucose is oxidised to carbon dioxide and oxygen is reduced to water. The energy released in the process is stored in the form of ATPs. 36 to 38 ATPs are formed from each glucose molecule.
The Four Stages are:
Glycolysis: Partial oxidation of a glucose molecule to form 2 molecules of pyruvate. This process takes place in the cytosol.
Formation of Acetyl CoA: Pyruvate formed in glycolysis enters the mitochondrial matrix. It undergoes oxidative decarboxylation to form two molecules of Acetyl CoA. The reaction is catalysed by pyruvate dehydrogenase enzyme.
Krebs Cycle (TCA or Citric Acid Cycle): It is the common pathway for complete oxidation of carbohydrates, proteins and lipids as they are metabolised to acetyl coenzyme A or other intermediates of the cycle.The Acetyl CoA produced enters the Tricarboxylic acid cycle or Citric acid cycle. Glucose is fully oxidised in this process. The acetyl CoA combines with oxaloacetate (4C) to form citrate (6C). In this process, 2 molecules of CO₂ are released and oxaloacetate is recycled. Energy is stored in ATP and other high energy compounds like NADH and FADH₂.
Electron Transport System and Oxidative Phosphorylation: ATP is generated when electrons are transferred from the energy-rich molecules like NADH and FADH₂, produced in glycolysis, citric acid cycle and fatty acid oxidation to molecular O₂ by a series of electron carriers. O₂ is reduced to H₂O. It takes place in the inner membrane of mitochondria.
Krebs Cycle Steps
It is an eight-step process. Krebs cycle takes place in the matrix of mitochondria under aerobic condition.
Step 1: First step is the condensation of acetyl CoA with oxaloacetate (4C) to form citrate (6C), coenzyme A is released. The reaction is catalysed by citrate synthase.
Step 2: Citrate is turned to its isomer, isocitrate. The enzyme aconitase catalyses this reaction.
Step 3: Isocitrate undergoes dehydrogenation and decarboxylation to form 𝝰-ketoglutarate (5C). A molecular of CO₂ is released. Isocitrate dehydrogenase catalyses the reaction. It is an NAD+ dependent enzyme. NAD+ is converted to NADH.
Step 4: α-ketoglutarate (5C) undergoes oxidative decarboxylation to form succinyl CoA (4C). 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 is converted to succinate by the enzyme succinyl CoA synthetase. This is coupled with substrate-level phosphorylation of GDP to form GTP. GTP transfers its phosphate to ADP forming ATP.
Step 6: Succinate is oxidised to fumarate by the enzyme succinate dehydrogenase. In the process, FAD is converted to FADH₂.
Step 7: Fumarate gets converted to malate by 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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Krebs Cycle Summary
Location: Krebs cycle occurs in the mitochondrial matrix
Krebs Cycle Reactants: Acetyl CoA, which is produced from the end product of glycolysis, i.e. pyruvate and it condenses with 4 carbon oxaloacetate, which is generated back in the Krebs cycle
Krebs Cycle Products
Each citric acid cycle forms the following products:
2 molecules of CO₂ are released. Removal of CO₂ or decarboxylation of citric acid takes place at two places:
In the conversion of isocitrate (6C) to α-ketoglutarate (5C)
In the conversion of α-ketoglutarate (5C) to succinyl CoA (4C)
1 ATP is produced in the conversion of succinyl CoA to succinate
3 NAD+ are reduced to NADH and 1 FAD+ is converted to FADH₂ in the following reactions:
Isocitrate to α-ketoglutarate → NADH
α-ketoglutarate to succinyl CoA → NADH
Succinate to fumarate → FADH₂
Malate to Oxaloacetate → NADH
Note that 2 molecules of Acetyl CoA are produced from oxidative decarboxylation of 2 pyruvates so two cycles are required per glucose molecule.
To summarize, for complete oxidation of a glucose molecule, Krebs cycle yields 4 CO₂, 6NADH, 2 FADH₂ and 2 ATPs.
Each molecule of NADH can form 2-3 ATPs and each FADH₂ gives 2 ATPs on oxidation in the electron transport chain.
Krebs Cycle Equation
To Sum up
Significance of Krebs Cycle
Krebs cycle or Citric acid cycle is the final pathway of oxidation of glucose, fats and amino acids.
Many animals are dependent on nutrients other than glucose as an energy source.
Amino acids (metabolic product of proteins) are deaminated and get converted to pyruvate and other intermediates of the Krebs cycle. They enter the cycle and get metabolised e.g. alanine is converted to pyruvate, glutamate to α-ketoglutarate, aspartate to oxaloacetate on deamination.
Fatty acids undergo β-oxidation to form acetyl CoA, which enters the Krebs cycle.
It is the major source of ATP production in the cells. A large amount of energy is produced after complete oxidation of nutrients.
It plays an important role in gluconeogenesis and lipogenesis and interconversion of amino acids.
Many intermediate compounds are used in the synthesis of amino acids, nucleotides, cytochromes and chlorophylls, etc.
Vitamins play an important role in the citric acid cycle. Riboflavin, niacin, thiamin and pantothenic acid as a part of various enzymes cofactors (FAD, NAD) and coenzyme A.
Regulation of Krebs cycle depends on the supply of NAD+ and utilization of ATP in physical and chemical work.
The genetic defects of the Krebs cycle enzymes are associated with neural damage.
As most of the processes occur in the liver to a significant extent, damage to liver cells has a lot of repercussions. Hyperammonemia occurs in liver diseases and leads to convulsions and coma. This is due to reduced ATP generation as a result of the withdrawal of α-ketoglutarate and formation of glutamate, which forms glutamine.
Q1. What is the Krebs Cycle?
Ans. Also known as the citric acidity cycle, Kreb’s cycle is a chain of reactions occurring in the mitochondria, through which almost all living cells produce energy in aerobic respiration. It consumes oxygen to give out water and carbon dioxide are products. Here , ADP is converted into ATP. This cycle renders electrons and hydrogen required for the electron chain transport.
Q2. How Many ATP are Produced in Krebs Cycle?
Ans. 2 ATPs are produced in one Krebs Cycle.For complete oxidation of a glucose molecule, Krebs cycle yields 4 CO₂, 6NADH, 2 FADH₂ and 2 ATPs.
Q3. Where Does Krebs Cycle Occur?
Ans. Mitochondrial matrix. In all eukaryotes, mitochondria is the site where Krebs cycle takes place. The cycle takes place in a mitochondrial matrix producing a chemical energy in the form of NADH, ATP, FADH₂. These are produced as a result of oxidation of the end product of glycolysis – pyruvate.
Q4. How the Krebs Cycle Works?
Ans. It is a Eight Step Process
Condensation of acetyl CoA with oxaloacetate (4C) forming citrate (6C), coenzyme A is released.
Conversion of Citrate to its isomer, isocitrate.
Isocitrate is subjected to dehydrogenation and decarboxylation forming α-ketoglutarate (5C).
α-ketoglutarate (5C) experiences oxidative decarboxylation forming succinyl CoA (4C).
Conversion of Succinyl CoA to succinate by succinyl CoA synthetase enzyme along with substrate-level phosphorylation of GDP forming GTP.
Fumarate gets converted to malate by addition of one H₂O.
Malate is dehydrogenated to form oxaloacetate, which combines with another molecule of acetyl CoA and starts the new cycle.
Q5. Why is Krebs Cycle Called an Amphibolic Pathway?
Ans. It is called amphibolic as in the Krebs cycle both catabolism and anabolism takes place. Amphibolic pathway indicates the one involving both catabolic and anabolic procedures.