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.
The Krebs cycle can be defined as an eight-step process occurring in the mitochondrial matrix. Acetyl CoA, derived from carbohydrates, proteins and fats is completely oxidised to release carbon dioxide. In the form of ATP, the energy released is stored. The eight steps involved are –
Step 1: The 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 catalysed 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 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.
1. The Product Essential for Oxidative Phosphorylation in the Krebs Cycle is _______
(a) NADPH and ATP
(b) Acetyl CoA
(c) CO2 and oxaloacetate
(d) NADH and FADH2
Answer: (d)
2. A Single-Molecule of Glucose Generates _________ Molecules of Acetyl CoA, Which Enters the Krebs Cycle.
(a) 4
(b) 3
(c) 2
(d) 1
Answer: (c)
3. ___________ Accepts Hydrogen from Malate
(a) FAD
(b) NAD
(c) NADP
(d) FMN
Answer: (b)
4. Which of the Intermediate of the Krebs Cycle Is Utilised in the Formation of Amino Acids
(a) Citric acid
(b) Malic acid
(c) Isocitric acid
(d) 𝛼-ketoglutaric acid
Answer: (d)
5. Krebs Cycle Takes Place in Aerobic Respiration Due To
(a) Electron transport chain requires aerobic conditions to operate
(b) Oxygen is a reactant
(c) Oxygen has a catalytic function
(d) All of the above
Answer: (a)
6. Acetyl CoA is Formed from Pyruvate By__________ Reaction
(a) Dehydration
(b) Reduction
(c) Oxidative decarboxylation
(d) Dephosphorylation
Answer: (c)
7. Which of the Following is Not Formed During the Krebs Cycle
(a) Lactate
(b) Isocitrate
(c) Succinate
(d) Both (a) and (b)
Answer: (a)
8. The Arrival of Pyruvate Into the TCA Cycle Is Inhibited by the Presence of a High Cellular Concentration Of
(a) Pyruvate
(b) NADH
(c) Coenzyme A
(d) AMP
Answer: (b)
9. ATP Synthase is Powered By
(a) Coenzyme motive force
(b) CAMP
(c) Proton gradient
(d) GTP hydrolysis
Answer: (c)
10. FAD is Reduced in Which of the Reactions of the Kreb’s Cycle?
(a) Isocitrate to oxaloacetate
(b) Succinyl CoA to Succinate
(c) Fumarate to malate
(d) Succinate to fumarate
Answer: (d)
The Krebs cycle, also known as the Citric acid cycle, is a sequence of enzyme-catalysed events that occur in the mitochondrial matrix and involve the oxidation of acetyl-CoA to make carbon dioxide and the reduction of coenzymes, both of which generate ATP in the electron transport chain.
The Krebs cycle was named after Hans Krebs, the man who proposed the detailed cycle. In 1953, he was awarded the Nobel Prize for his work.
It is an eight-step process in which the acetyl group of acetyl-CoA is oxidised to make two molecules of CO2 and one ATP is produced. NADH and FADH2 are also generated as reduced high energy molecules.
The Krebs Cycle is a Component of Cellular Respiration
Cellular respiration is a catabolic activity that occurs within cells. It is a biological process that breaks down nutrients to generate energy, which is stored in the form of ATP, while waste products are discharged. Aerobic respiration necessitates the use of oxygen.
Because each glucose molecule produces two molecules of acetyl-CoA, two cycles of the Krebs cycle are required, yielding four CO2, six NADH, two FADH2, and two ATPs.
Cellular respiration occurs in four stages. During the process, glucose is converted to carbon dioxide and oxygen is converted to water. The energy released throughout the process is stored as ATPs. Each glucose molecule produces 36 to 38 ATPs.
The four stages are as follows:
1. Glycolysis: The partial oxidation of a glucose molecule to produce two pyruvate molecules. This process occurs in the cytoplasm.
2. Acetyl CoA Synthesis: Pyruvate from glycolysis enters the mitochondrial matrix. It is oxidatively decarboxylated to produce two molecules of Acetyl CoA. The pyruvate dehydrogenase enzyme catalyses the process.
3. The Krebs Cycle (TCA or Citric Acid Cycle) is the usual mechanism for the full oxidation of carbohydrates, proteins, and lipids as they are metabolised to acetyl coenzyme A or other cycle intermediates. The generated Acetyl CoA joins the Tricarboxylic acid cycle or the Citric acid cycle. This method completely oxidises glucose. The 6-carbon molecule acetyl CoA reacts with the 4-carbon compound oxaloacetate to generate 6C citrate. Two molecules of CO2 are emitted during this process, and oxaloacetate is recycled. ATP and other high energy molecules such as NADH and FADH2 store energy.
4. Electron Transport System and Oxidative Phosphorylation: ATP is created when electrons are transferred to molecular O2 by a series of electron carriers from energy-rich molecules such as NADH and FADH2 produced in glycolysis, citric acid cycle, and fatty acid oxidation. H2O is formed by converting O2 to H2O. It takes place in the inner membrane of mitochondria.
Steps in the Krebs Cycle
It’s an eight-step procedure. Under aerobic conditions, the Krebs cycle occurs in the matrix of mitochondria.
Step 1: Coenzyme A is released during the condensation of acetyl CoA with the 4-carbon molecule oxaloacetate to create 6C citrate. Citrate synthase catalyses the process.
Step 2: Isocitrate is formed by converting citrate to its isomer, isocitrate. This process is catalysed by the enzyme aconitase.
Step 3: Isocitrate is dehydrogenated and decarboxylated to produce 5C-ketoglutarate. CO2 in the molecular form is emitted. The process is catalysed by isocitrate dehydrogenase. It is an NAD+ requiring enzymes. NADH is formed via the conversion of NAD+.
Step 4: -ketoglutarate is decarboxylated oxidatively to create succinyl CoA, a 4C molecule. The -ketoglutarate dehydrogenase enzyme complex catalyses the process. NAD+ is transformed to NADH and one molecule of CO2 is liberated.
Step 5: Succinate is formed by succinyl CoA. The process is catalysed by the enzyme succinyl CoA synthetase. This is followed by substrate-level phosphorylation of GDP to produce GTP. GTP phosphates ADP, resulting in the formation of ATP.
Step 6: Succinate is oxidised to fumarate by the enzyme succinate dehydrogenase. FAD is transformed to FADH2 throughout the process.
Step 7: By adding one H2O, fumarate is transformed to malate. Fumarase is the enzyme that catalyses this reaction.
Step 8: Malate is dehydrogenated to produce oxaloacetate, which joins with another acetyl CoA molecule to initiate the next cycle. Hydrogens are removed and transferred to NAD+, resulting in the formation of NADH. The process is catalysed by malate dehydrogenase.
Summary of the Krebs Cycle Location: The Krebs cycle takes place in the mitochondrial matrix.
Acetyl CoA is formed from the end result of glycolysis, pyruvate, and condenses with 4 carbon oxaloacetate, which is produced again in the Krebs cycle.
Products of the Krebs Cycle
The following compounds are produced throughout each citric acid cycle:
Two molecules of CO2 are emitted. CO2 is removed or citric acid is decarboxylated in two places:
In the process of converting isocitrate (6C) to -ketoglutarate (5C)
In the process of converting -ketoglutarate (5C) to succinyl CoA (4C)
When succinyl CoA is converted to succinate, one ATP is generated.
In the following reactions, 3 NAD+ are reduced to NADH and 1 FAD+ is transformed to FADH2:
NADH isocitrate to -ketoglutarate
NADH to succinyl CoA -ketoglutarate
FADH2 Malate to Oxaloacetate NADH Succinate to fumarate
Because oxidative decarboxylation of two pyruvates yields two molecules of acetyl CoA, two cycles are required per glucose molecule.
To summarise, the Krebs cycle produces 4 CO2, 6 NADH, 2 FADH2, and 2 ATPs for the full oxidation of a glucose molecule.
On oxidation in the electron transport chain, each NADH molecule can produce 2-3 ATPs, while each FADH2 molecule produces 2 ATPs.
The Krebs Cycle’s Importance
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The Krebs cycle, also known as the Citric acid cycle, is the last mechanism for the oxidation of glucose, lipids, and amino acids.
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Many animals rely on substances other than glucose as a source of energy.
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Amino acids (protein metabolic products) are deaminated and transformed to pyruvate and other Krebs cycle intermediates. On deamination, they enter the cycle and are metabolised, for example, alanine is transformed to pyruvate, glutamate to -ketoglutarate, and aspartate to oxaloacetate.
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Fatty acids are -oxidised to produce acetyl CoA, which enters the Krebs cycle.
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It is the most important source of ATP generation in cells. After full nutrient oxidation, a considerable amount of energy is created.
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It is essential for gluconeogenesis, lipogenesis, and amino acid interconversion.
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Many intermediate molecules are utilised in the production of amino acids, nucleotides, cytochromes, chlorophylls, and other organic chemicals.
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Vitamins are essential components of the citric acid cycle. Riboflavin, niacin, thiamin, and pantothenic acid are cofactors and coenzymes for numerous enzymes (FAD, NAD). The Krebs cycle is regulated by the availability of NAD+ and the usage of ATP in physical and chemical activities.
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Neurological injury is linked to hereditary abnormalities in Krebs cycle enzymes.
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Because the liver is responsible for the majority of biological activities, injury to liver cells has a wide range of consequences. Hyperammonemia is a complication of liver illness that causes convulsions and unconsciousness. This is related to decreased ATP synthesis as a result of -ketoglutarate withdrawal and the creation of glutamate, which generates glutamine.