Krebs Cycle or Citric Acid Cycle
The Krebs cycle or Citric acid cycle is a series of enzyme-catalyzed reactions occurring in the mitochondrial matrix, where acetyl-CoA is oxidized 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 oxidized to form two molecules of \[CO_{2}\] and in the process, one ATP is produced. Reduced high-energy compounds, NADH, and \[FADH_{2}\] 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 \[CO_{2}\], 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 oxidized 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 catalyzed by the pyruvate dehydrogenase enzyme.
\[2Pyruvate + 2NAO^{-} + 2CoA^{-} \overset{ Pyruvate dehydrogenase }{\rightarrow} 2 Acetyl CoA + 2NADH + C0_{2}\]
Krebs Cycle (TCA or Citric Acid Cycle): It is the common pathway for complete oxidation of carbohydrates, proteins, and lipids as they are metabolized 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 oxidized in this process. The acetyl CoA combines with oxaloacetate (4C) to form citrate (6C). In this process, 2 molecules of \[CO_{2}\] are released and oxaloacetate is recycled. Energy is stored in ATP and other high-energy compounds like NADH and \[FADH_{2}\].
Electron Transport System and Oxidative Phosphorylation: ATP is generated when electrons are transferred from the energy-rich molecules like NADH and \[FADH_{2}\] produced in glycolysis, citric acid cycle, and fatty acid oxidation to molecular \[O_{2}\] by a series of electron carriers. \[O_{2}\] is reduced to \[H_{2}O\]. It takes place in the inner membrane of mitochondria.
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 oxaloacetate (4C) to form citrate (6C), coenzyme A is released. The reaction is catalyzed by citrate synthase.
Step 2: Citrate is turned to its isomer, isocitrate. The enzyme aconitase catalyzes this reaction.
Step 3: Isocitrate undergoes dehydrogenation and decarboxylation to form 𝝰-ketoglutarate (5C). A molecular of \[CO_{2}\] is released. Isocitrate dehydrogenase catalyzes 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 the α-ketoglutarate dehydrogenase enzyme complex. One molecule of \[CO_{2}\] 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 oxidized to fumarate by the enzyme succinate dehydrogenase. In the process, FAD is converted to \[FADH_{2}\].
Step 7: Fumarate gets converted to malate by the addition of one \[H_{2}O\]. The enzyme catalyzing 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 catalyzes the reaction.
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 \[CO_{2}\] are released. Removal of \[CO_{2}\] 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 \[FADH_{2}\] in the following reactions:
Isocitrate to α-ketoglutarate → NADH
α-ketoglutarate to succinyl CoA → NADH
Succinate to fumarate → \[FADH_{2}\]
Malate to Oxaloacetate → NADH
Notes 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, the Krebs cycle yields \[ 4 CO_{2}, 6NADH, 2 FADH_{2} \], 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,
\[ 2 Acytyl CoA + 6 NAO^{-} + 2 FAD + 2ADP + 2P_{i} + 2H_{2}0 \rightarrow 4CO_{2} + 6 NADH + 2FADH_{2} + 2ATP + CoA \]
Significance of Krebs Cycle
The 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 metabolized 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 the complete oxidation of nutrients.
It plays an important role in gluconeogenesis lipogenesis and interconversion of amino acids.
Many intermediate compounds are used in the synthesis of amino acids, nucleotides, cytochromes, chlorophylls, etc.
Vitamins play an important role in the citric acid cycle. Riboflavin, niacin, thiamin, and pantothenic acid a part of various enzymes cofactors (FAD, NAD) and coenzyme A.
Regulation of the Krebs cycle depends on the supply of NAD+ and the 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 the formation of glutamate, which forms glutamine.
FAQs on Krebs Cycle
1. What is the Krebs Cycle?
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 is the product. Here, ADP is converted into ATP. This cycle renders electrons and hydrogen required for electron chain transport.
2. How Many ATP are Produced in Krebs Cycle?
2 ATPs are produced in one Krebs Cycle. For complete oxidation of a glucose molecule, the Krebs cycle yields \[4 CO_{2}\], 6NADH, \[2 FADH_{2}\], and 2 ATPs.
3. Where Does Krebs Cycle Occur?
Mitochondrial matrix. In all eukaryotes, mitochondria are the site where the Krebs cycle takes place. The cycle takes place in a mitochondrial matrix producing chemical energy in the form of NADH, ATP, \[FADH_{2}\]. These are produced as a result of oxidation of the end product of glycolysis – pyruvate.
4. How does the Krebs Cycle Works?
It is an 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 the addition of one \[H_{2}O\].
Malate is dehydrogenated to form oxaloacetate, which combines with another molecule of acetyl CoA and starts the new cycle.
5. Why is Krebs Cycle Called an Amphibolic Pathway?
It is called amphibolic as in the Krebs cycle both catabolism and anabolism take place. The amphibolic pathway indicates the one involving both catabolic and anabolic procedures.
6. What is the Krebs cycle?
The Krebs cycle is a process that occurs in one of the most significant reaction sequences in biochemistry is the Krebs cycle, commonly known as the citric acid cycle or the tricarboxylic acid cycle. Not only are the molecules produced in these reactions responsible for the majority of the energy needs in complex organisms, but they can also be used as building blocks for a lot of crucial processes. Synthesis of fatty acids, steroids, cholesterol, amino acids for protein building, and the purines and pyrimidines are used in DNA synthesis. Lipids (fats) and carbohydrates, which both create the chemical acetyl coenzyme-A, provide energy for the Krebs cycle (acetyl-CoA).
This acetyl-CoA reacts in the first of the eight steps that make up the Krebs cycle, which all take place inside the mitochondria of eukaryotic cells. As the Krebs cycle produces carbon dioxide, it does not directly generate significant chemical energy in the form of adenosine triphosphate (ATP), nor does it make the use of oxygen necessary. This cycle produces NADH and \[FADH_{2}\], which are fed into the respiratory cycle, which is likewise confined inside the mitochondria.
The process of the citric acid cycle takes place in the matrix of the mitochondria in eukaryotic cells. The citric acid cycle reaction sequence takes place in the cytosol in prokaryotic cells without mitochondria, like bacteria, with the proton gradient for ATP synthesis being across the cell rather than the inner membrane of the mitochondrion. The TCA cycle produces three NADH, one \[FADH_{2}\], and one GTP as a total yield of energy-containing molecules.
7. What is the biochemistry of muscle mitochondria?
The hydrogen atoms (or the electrons derived from them) do not react directly with oxygen in the Krebs cycle oxidation processes; instead, they transit via a succession of hydrogen or electron carriers, known as the respiratory chain.
The lipoic acid covalently linked to one of the proteins of the corresponding keto–acid dehydrogenase complex is the major hydrogen acceptor for the oxidation of pyruvate and -ketoglutarate. In a process catalyzed by lipoamide dehydrogenase, hydrogens from reduced lipoic acid are transported to NAD+. NAD+ also functions as a hydrogen acceptor for the oxidation of a lot of substrates. Malate, isocitrate, and l-3-hydroxy acyl-CoA, with each oxidoreduction, get mediated by a different dehydrogenase.
8. What is the biochemistry of muscle mitochondria?
The steps in the Krebs cycle are:
The TCA cycle starts with an enzymatic aldol addition reaction of acetyl CoA to oxaloacetate, which results in the formation of citrate.
A dehydration-hydration sequence is used to isomerize citrate, yielding (2R,3S)-isocitrate.
2-ketoglutarate is formed after more enzymatic oxidation and decarboxylation.
2-ketoglutarate is converted to succinyl-CoA after more enzymatic decarboxylation and oxidation.
The phosphorylation of guanosine diphosphate (GDP) to guanosine triphosphate is connected to the hydrolysis of this metabolite to succinate (GTP).
Fumarate is generated by the enzyme flavin adenine dinucleotide (FAD)-dependent succinate dehydrogenase.
Fumarate catalyzed by fumarase is changed to L-malate after going through stereospecific hydration.
Malate dehydrogenase catalyzes the final step of NAD-coupled oxidation of L-malate to oxaloacetate, which completes the cycle.
9. What is the efficiency of the Krebs cycle?
The theoretical maximal yield of ATP from glycolysis, the citric acid cycle, and oxidative phosphorylation is 38. Glycolysis, which occurs in the cytoplasm of eukaryotes, produces two equivalents of NADH and four equivalents of ATP. The transport of two equivalents of NADH into the mitochondria uses two equivalents of ATP, lowering the net ATP production to 36. Furthermore, oxidative phosphorylation inefficiencies caused by proton leakage across the mitochondrial membrane and ATP synthase/proton pump slippage typically lower ATP yield from NADH and \[FADH_{2}\], to less than the theoretical maximum output. As a result, the observed yields are closer to 2.5 ATP per NADH and 1.5 ATP per
\[FADH_{2}\], lowering the total net ATP generation to around 30.
Based on freshly revised proton-to-ATP ratios, the total ATP yield is estimated to be 29.85 ATP per glucose molecule.
10. What is the role of the Krebs cycle in the metabolism of carbohydrates?
The role of mitochondria in oxidative phosphorylation has already been discussed, as has their role in carbohydrate metabolism due to the presence of enzymes involved in the Krebs cycle and cytochrome system in their substance. Then, we should brood regarding glucose metabolism and the role that mitochondria and other cytoplasm components have in it.
Carbohydrate metabolism is critical for cell synthesis and serves as the primary source of energy for cell functions. Before we try to pinpoint where the various functions of glucose metabolism occur in the cell, let's have a look at what carbohydrate metabolism entails. Anaerobic and aerobic metabolism are the two forms of metabolism. Head to the Vedantu app and website for free study materials.
