Location, Enzymes, Steps, Merchandise, Diagram

The Krebs cycle, also called the citric acid cycle or TCA cycle, is a collection of reactions that happen within the mitochondria, ensuing within the oxidation of acetyl CoA to launch carbon dioxide and hydrogen atoms that later result in the formation of water.

• This cycle is termed the citric acid cycle as the primary metabolic intermediate fashioned within the cycle is citric acid.
• This cycle can be termed tricarboxylic acid (TCA) as a result of it was then not sure whether or not citric acid or another tricarboxylic acid (g., isocitric acid) was the primary product of the cycle. Nonetheless, now it has been recognized that the primary product is certainly citric acid and thus using this title has since been discouraged.
• This cycle solely happens below cardio situations as energy-rich molecules like NAD⁺ and FAD can solely be retrieved from their lowered type as soon as they switch electrons to molecular oxygen.
• The citric acid cycle is the ultimate widespread pathway for the oxidation of all biomolecules; proteins, fatty acids, carbohydrates. Molecules from different cycles and pathways enter this cycle by means of Acetyl CoA.
• The citric acid cycle is a cyclic sequence of reactions fashioned of 8 enzyme-mediated reactions.
• This cycle can be notably essential because it gives electrons/ high-energy molecules to the electron transport chain for the manufacturing of ATPs and water.
• Pyruvate fashioned on the finish of glycolysis is first oxidized into Acetyl CoA which then enters the citric acid cycle.

Krebs Cycle Location

• The citric acid cycle in eukaryotes takes place within the mitochondria whereas in prokaryotes, it takes place within the cytoplasm.
• The pyruvate fashioned within the cytoplasm (from glycolysis) is introduced into the mitochondria the place additional reactions happen.
• The totally different enzymes concerned within the citric acid cycle are positioned both within the internal membrane or within the matrix house of the mitochondria.

Krebs Cycle Equation/ Response

The general response/ equation of the citric acid cycle is:

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

In phrases, 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, the enzymes that catalyze the reactions of the citric acid cycle are current within the matrix of the mitochondria aside from succinate dehydrogenase and aconitase, that are current within the internal mitochondrial membrane.

One widespread attribute in all of the enzymes concerned within the citric acid cycle is that almost all of them require Mg²⁺

The next are the enzymes that catalyze totally different steps all through the method of the citric acid cycle:

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

Determine: Reactions of the citric acid cycle. Picture Supply: Lehninger Rules of Biochemistry.

Video of Krebs Cycle

Krebs Cycle Steps

After glycolysis, in cardio organisms, the pyruvate molecules are carboxylated to type acetyl CoA and CO₂.

Oxidative Decarboxylation of pyruvate to Acetyl CoA

Picture Supply: Lehninger Rules of Biochemistry.

• The oxidative decarboxylation of pyruvate kinds a hyperlink between glycolysis and the citric acid cycle.
• On this course of, the pyruvate derived from glycolysis is oxidatively decarboxylated to acetyl CoA and CO₂ catalyzed by the pyruvate dehydrogenase complicated within the mitochondrial matrix in eukaryotes and within the cytoplasm of the prokaryotes.
• From one molecule of glucose, two molecules of pyruvate are fashioned, every of which kinds one acetyl CoA together with one NADH by the top of the pyruvate oxidation.
• The acetyl CoA fashioned from pyruvate oxidation, fatty acid metabolism, and amino acid pathway then enter the citric acid cycle.

The next are the eight enzyme-catalyzed reactions/ steps within the cardio oxidation of glucose by means of the citric acid cycle:

Step 1: Condensation of acetyl CoA with oxaloacetate

Picture Supply: Lehninger Rules of Biochemistry.

• Step one of the citric acid cycle is the becoming a member of of the four-carbon compound oxaloacetate (OAA) and a two-carbon compound acetyl CoA.
• The oxaloacetate reacts with the acetyl group of the acetyl CoA and water, ensuing within the formation of a six-carbon compound citric acid, CoA.
• The response is catalyzed by the enzyme citrate synthase that condenses the methyl group of acetyl CoA and the carbonyl group of oxaloacetate leading to citryl-CoA which is later cleaved to free coenzyme A and to type citrate.

Step 2: Isomerization of citrate into isocitrate

Picture Supply: Lehninger Rules of Biochemistry.

• Now, for additional metabolism, citrate is transformed into isocitrate by means of the formation of intermediate cis-aconitase.
• This response is a reversible response catalyzed by the enzyme aconitase.
• This response takes place by a two-step course of the place step one entails dehydration of citrate to cis-aconitase, adopted by the second step involving rehydration of cis-aconitase into isocitrate.

Step 3: Oxidative decarboxylations of isocitrate

Picture Supply: Lehninger Rules of Biochemistry.

• The third step of the citric acid cycle is the primary of the 4 oxidation-reduction reactions on this cycle.
• Isocitrate is oxidatively decarboxylated to type a five-carbon compound, α-ketoglutarate catalyzed by the enzyme isocitrate dehydrogenase.
• This response, just like the second response, is a two-step response.
• In step one, isocitrate is dehydrogenated to oxalosuccinate whereas the second step entails the decarboxylation of oxalosuccinate to α-ketoglutarate.
• Each the reactions are irreversible and catalyzed by the identical enzyme.
• Step one, nonetheless, ends in the formation of NADH whereas the second step entails the discharge of CO₂.

Step 4: Oxidative decarboxylation of α-ketoglutarate

Picture Supply: Lehninger Rules of Biochemistry.

• This step is one other one of many oxidation-reduction reactions the place α-ketoglutarate is oxidatively decarboxylated to type a four-carbon compound, succinyl-CoA, and CO₂.
• The response irreversible and catalyzed by the enzyme complicated α-ketoglutarate dehydrogenase discovered within the mitochondrial house.
• This response is much like the oxidative decarboxylation of pyruvate involving the discount of NAD⁺ into NADH.

Step 5: Conversion of succinyl-CoA into succinate

Picture Supply: Lehninger Rules of Biochemistry.

• Within the subsequent step, succinyl-CoA undergoes an energy-conserving response during which succinyl-CoA is cleaved to type succinate.
• This response is accompanied by phosphorylation of guanosine diphosphate (GDP) to guanosine triphosphate (GTP).
• The GTP thus fashioned then readily transfers its terminal phosphate group to ADP forming an ATP molecule.
• The response is catalyzed by the enzyme, succinyl-CoA synthase.

Step 6: Dehydration of succinate to fumarate

Picture Supply: Lehninger Rules of Biochemistry.

• Right here, the succinate fashioned from succinyl-CoA is dehydrogenated to fumarate catalyzed by the enzyme complicated succinate dehydrogenase discovered within the intramitochondrial house.
• That is the one dehydrogenation step within the citric acid cycle during which NAD⁺ doesn’t take part.
• As an alternative, one other high-energy electron provider, flavin adenine dinucleotide (FAD) acts because the hydrogen acceptor ensuing within the formation of FADH₂.
• The FADH₂ then enters the electron transport chain by way of the complicated II transferring the electrons to ubiquinone, lastly forming 2ATPs.

Step 7: Hydration of fumarate to malate

Picture Supply: Lehninger Rules of Biochemistry.

• The fumarate is reversibly hydrated to type L-malate within the presence of the enzyme fumarate hydratase.
• As it’s a reversible response, the formation of L-malate entails hydration, whereas the formation of fumarate entails dehydration.

Step 8: Dehydrogenation of L-malate to oxaloacetate

Picture Supply: Lehninger Rules of Biochemistry.

• The final step of the citric acid cycle can be an oxidation-reduction response the place L-malate is dehydrogenated to oxaloacetate within the presence of L-malate dehydrogenase, which is current within the mitochondrial matrix.
• This can be a reversible response involving oxidation of L-malate and discount of NAD⁺ into NADH.
• Oxaloacetate thus fashioned, permits the repetition of the cycle and NADH fashioned participates within the oxidative phosphorylation.
• This response completes the cycle.

Krebs Cycle Merchandise

Since this can be a cyclic course of, the oxaloacetate is fashioned on the finish because it condenses with acetyl CoA within the subsequent cycle.

Determine: Merchandise of 1 flip of the citric acid cycle. Picture Supply: Lehninger Rules of Biochemistry.

At every flip of the cycle,

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

Observe: One NADH are fashioned from a molecule of pyruvate within the oxidative decarboxylation of pyruvate to Acetyl CoA.

Krebs Cycle FAQs and Observe Questions

Krebs Cycle Music