Krebs cycle, Definition, Location, Enzymes, Products and Steps

Krebs cycle Definition

The Krebs cycle, also known as the citric acid cycle or TCA cycle, is a series of reactions that take place in the mitochondria that results in the oxidation of acetyl CoA to release carbon dioxide and hydrogen atoms that then lead to water formation.

Krebs cycle, Definition, Location, Enzymes, Products and Steps
  • This cycle is called the citric acid cycle since the first metabolic intermediate formed in the cycle is citric acid.
  • This cycle is also called tricarboxylic acid (TCA) because you were not sure if citric acid or some other tricarboxylic acid (eg isocyanic acid) was the first product in the cycle. However, it is now known that the first product is citric acid and the use of this name is therefore discouraged.
  • This cycle only occurs under aerobic conditions, since energy-rich molecules like NAD + and FAD can only recover from their reduced form once they transfer electrons to molecular oxygen.
  • The citric acid cycle is the common final pathway for oxidation of all biomolecules; proteins, fatty acids, carbohydrates. Molecules from other cycles and pathways enter this cycle through Acetyl CoA.
  • The citric acid cycle is a cyclic sequence of reactions consisting of 8 enzyme-mediated reactions.
  • This cycle is also particularly important as it provides high energy electrons/molecules to the electron transport chain for the production of ATP and water.
  • The pyruvate formed at the end of glycolysis is first oxidized to Acetyl CoA, which then enters the citric acid cycle.

Krebs cycle Location

  • The citric acid cycle in eukaryotes takes place in the mitochondria, while in the prokaryotes it takes place in the cytoplasm.
  • Pyruvate formed in the cytoplasm (from glycolysis) is introduced into the mitochondria, where other reactions occur.
  • The different enzymes involved in the citric acid cycle are found on the inner membrane or in the matrix space of the mitochondria.

Krebs cycle Equation/ Reaction

Krebs cycle, Definition, Location, Enzymes, Products and Steps

The overall reaction/ equation of the citric acid cycle is:

Acetyl CoA + 3 NAD+ + 1 FAD + 1 ADP + 1 Pi → 2 CO2 + 3 NADH + 3 H+ + 1 FADH2 + 1 ATP

In words, the equation is written as:

Acetyl CoA + Nicotinamide adenine dinucleotide + Flavin adenine dinucleotide + Adenosine diphosphate + Phosphate → Pyruvate + Water + Adenosine triphosphate + Nicotinamide adenine dinucleotide + Hydrogen ions

Krebs cycle Enzymes

In eukaryotic cells, enzymes that catalyze citric acid cycle reactions are present in the matrix of mitochondria, except succinate dehydrogenase and aconitase, which are present in the inner mitochondrial membrane.

A common feature of all enzymes involved in the citric acid cycle is that almost all require Mg2 +

The following are the enzymes that catalyze different steps throughout the citric acid cycle process:

  1. Citrate synthase
  2. Aconitase
  3. Isocitrate dehydrogenase
  4. α-ketoglutarate
  5. Succinyl-CoA synthetase
  6. Succinate dehydrogenase
  7. Fumarase
  8. Malate dehydrogenase

Krebs cycle Steps

After glycolysis, in aerobic organisms, the pyruvate molecules are carboxylated to form acetyl CoA and CO2

Oxidative Decarboxylation of pyruvate to Acetyl CoA

  • The oxidative decarboxylation of pyruvate forms a link between glycolysis and the citric acid cycle.
  • In this process, pyruvate derived from glycolysis is oxidatively decarboxylated to acetyl CoA and CO2 catalyzed by the pyruvate dehydrogenase complex in the mitochondrial matrix in eukaryotes and in the cytoplasm of prokaryotes.
  • Two pyruvate molecules are formed from one glucose molecule, each of which forms an acetyl CoA together with an NADH at the end of the pyruvate oxidation.
  • Acetyl CoA formed from pyruvate oxidation, fatty acid metabolism, and the amino acid pathway enters the citric acid cycle.

Following are the eight enzyme-catalyzed reactions/steps in aerobic glucose oxidation through the citric acid cycle:

Step 1: Condensation of acetyl CoA with oxaloacetate

  • The first step in the citric acid cycle is the binding of the four-carbon oxaloacetate compound (OAA) and a two-carbon compound acetyl CoA.
  • Oxaloacetate reacts with the acetyl group of acetyl CoA and water, resulting in the formation of a six-carbon citric acid, CoA.
  • The reaction is catalyzed by the enzyme citrate synthase which condenses the methyl group of acetyl CoA and the carbonyl group of oxaloacetate, resulting in citryl-CoA, which is then cleaved to release coenzyme A and form citrate.

Step 2: Isomerization of citrate into isocitrate

  • Now, for increased metabolism, citrate is converted to isocitrate by the formation of intermediate cis-aconitase.
  • This reaction is a reversible reaction catalyzed by the enzyme (aconitase).
  • This reaction takes place by a two-step process in which the first step involves dehydration of citrate to cis-aconitase, followed by the second step involving rehydration of cis-aconitase in isocitrate.

Step 3: Oxidative decarboxylations of isocitrate

  • The third step in the citric acid cycle is the first of four oxidation-reduction reactions in this cycle.
  • The isocitrate is decarboxylated oxidatively to form a five-carbon compound, α-ketoglutarate catalyzed by the enzyme isocitrate dehydrogenase.
  • This reaction, like the second reaction, is a two-step reaction.
  • In the first step, the isocitrate is dehydrogenated to oxalosuccinate, while the second step involves decarboxylation of oxalosuccinate to α-ketoglutarate.
  • Both reactions are irreversible and catalyzed by the same enzyme.
  • However, the first step results in the formation of NADH, while the second step involves the release of CO2.

Step 4: Oxidative decarboxylation of α-ketoglutarate

  • This step is another of the oxidation-reduction reactions where the α-ketoglutarate is oxidatively decarboxylated to form a four-carbon compound, succinyl-CoA, and CO2.
  • The reaction is irreversible and catalyzed by the enzyme α-ketoglutarate dehydrogenase complex found in the mitochondrial space.
  • This reaction is similar to the oxidative decarboxylation of pyruvate that involves the reduction of NAD + in NADH.

Step 5: Conversion of succinyl-CoA into succinate

  • In the next step, succinyl-CoA undergoes an energy conservation reaction in which succinyl-CoA cleaves to form succinate.
  • This reaction is accompanied by phosphorylation of guanosine diphosphate (GDP) to guanosine triphosphate (GTP).
  • The GTP thus formed then easily transfers its terminal phosphate group to ADP forming an ATP molecule.
  • The reaction is catalyzed by the enzyme succinyl-CoA synthase.

Step 6: Dehydration of succinate to fumarate

  • Here, succinate formed from succinyl-CoA is dehydrogenated to fumarate catalyzed by the enzyme complex succinate dehydrogenase found in the intramitochondrial space.
  • This is the only dehydrogenation step in the citric acid cycle in which NAD + does not participate.
  • Instead, another high-energy electron carrier, flavin adenine dinucleotide (FAD) acts as the hydrogen acceptor that results in the formation of FADH2.
  • FADH2 then enters the electron transport chain through complex II transferring the electrons to ubiquinone, eventually forming 2ATP.

Step 7: Hydration of fumarate to malate

  • The fumarate is reversibly hydrated to form malate L in the presence of the enzyme fumarate hydratase.
  • As it is a reversible reaction, the formation of L-malate implies hydration, while the formation of fumarate implies dehydration.

Step 8: Dehydrogenation of L-malate to oxaloacetate

  • The last step in the citric acid cycle is also an oxidation-reduction reaction where L-malate is dehydrogenated to oxaloacetate in the presence of L-malate dehydrogenase, which is present in the mitochondrial matrix.
  • This is a reversible reaction involving the oxidation of L-malate and the reduction of NAD + in NADH.
  • The oxaloacetate thus formed allows the cycle to repeat and the NADH formed participates in oxidative phosphorylation.
  • This reaction completes the cycle.

Krebs cycle Products

Since this is a cyclic process, the oxaloacetate formed at the end as it condenses with acetyl CoA in the next cycle.

At each turn of the cycle,

  • 3 NADH,
  • 1 FADH2,
  • 1 GTP (or ATP),
  • 2 CO2

Note: One NADH is formed from a molecule of pyruvate in the oxidative decarboxylation of pyruvate to Acetyl CoA.

Krebs cycle, Definition, Location, Enzymes, Products and Steps

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Krebs cycle, Definition, Location, Enzymes, Products and Steps

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