Krebs cycle

Krebs cycle is also known as Citric acid cycle OR Tricarboxylic acid cycle OR Szent-Gyorgi-Krebs cycle. Acety CO-A produced from pyruvate via link reaction enters the Citric acid cycle, where it gets oxidised to carbon dioxide producing a pool of chemical energy(ATP, NADH and FADH2).

• Proposed by Sir Hans Krebs(1937)
• Happens in the mitochondrial matrix
• Complete oxidation of Acetyl CO-A into CO2
• As one glucose molecule produces two pyruvate molecule which in turn produces two Acetyl CO-A molecules, so there are two Krebs cycle for a single glucose molecule
• Enzymes for Krebs cycle present in mitochondrial matrix except for Succinate dehydrogenase, which is present in Inner mitochondrial membrane
• The acceptor of Acetyl CO-A is Oxaloacetate(OAA)

Pathway

Krebs cycle occurs in mitochondria when Acetyl CO-A enters into mitochondria. It is an amphibolic pathway as its intermediates are utilised in many anabolic pathways.

The citric acid cycle comprises of 8 steps-

Step- 1: Formation of Citrate

Acetyl CO-A reacts with Oxaloacetate in the presence of water to form Citric acid. The enzyme Citrate synthetase catalyses the reaction, in which Coenzyme A is regenerated.

Step- 2: Isomerisation of Citrate to Isocitrate

The enzyme Aconitase(Fe++ acts as a prosthetic group) removes a water molecule from Citric acid to form Cis-Aconitic acid, which is a dehydration reaction.

Cis-Aconitic acid is hydrated in the presence of Aconitase(Fe++ acts as a prosthetic group) to form Iso-Citric acid.

Step- 3: Formation of Alpha-ketoglutarate

The enzyme Isocitrate dehydrogenase reduces NAD+ to NADH thereby converting Iso-Citric acid to Oxalosuccinic acid.

The enzyme Decarboxylase removes a carbon dioxide molecule from Oxalosuccinic acid thus converting it into Alpha-ketoglutaric acid, which is a five-carbon compound.

Step- 4: Conversion of Alpha-ketoglutarate to Succinyl CO-A

Alpha-ketoglutarate Dehydrogenase reduces NAD+ to NADH and also removes carbon dioxide from Alpha-ketoglutaric acid to give Succinyl CO-A.

Step- 5: Formation of Succinate

On hydrolysis of Succinyl CO-A, Succinic acid and Coenzyme A are formed. The energy which is liberated is used to convert Guanine diphosphate to Guanine triphosphate(GDP-GTP). This one molecule of GTP generates one equivalent molecule ATP.

Step- 6: Conversion of Succinate to Fumarate

The enzyme Succinate dehydrogenase(found in Inner mitochondrial membrane) reduces FAD to FADH2 thereby producing Fumarate out of Succinate.

Step- 7: Formation of Malate

Fumarate hydrolyses Fumarate to produce Malate.

Step- 8: Conversion of Malate to Oxaloacetate

The enzyme Malate Dehydrogenase reduces NAD+ to NADH through the conversion of Malate to Oxaloacetate.

Summary of Citric acid cycle

Acetyl CO-A + 3 NAD+ +FAD +GDP +Inorganic phosphate+ 2 water = 2 Carbon dioxide + COA-SH + GTP + 3 NADH + 3 Hydrogen + FADH2

The fate of NADH and FADH2

These NADH and FADH2 molecules stores a large amount of energy stored in glucose. The energy stored in them needs to be extracted. Thus NADH and FADH2 produced in mitochondrial matrix travels to Inner mitochondrial membrane, where it enters the Electron Transport Chain(ETC). ETC is a series of complexes that transfer electrons from electron donors to electron acceptors via redox reactions and couples this electron transfer with the transfer of proton(H+ ions) across a membrane, which creates a proton gradient. This proton gradient helps in the production of ATP. Hence the energy stored in NADH and FADH2 extracted in the form of small packets called ATP.

Energetics

Oxidation of Acetyl CO-A in the Citric acid cycle is expressed by the following equation-

Acetyl CO-A + 2 O2 + GDP + Inorganic phosphate + 3 NAD+ + FAD = 2 Co2 + COA-SH + GTP + 3 NADH + 3 H+ + FADH2

Total ATP produced during the TCA cycle

Number of ATP generated by oxidation of 3 NADH = 9 ATP

Number of ATP generated by oxidation of FADH2 = 2 ATP

Number of ATP generated from GTP = 1 ATP

Total ATP production = 12 ATP

In Electron Transport Chain(ETC) each molecule of NADH, FADH2 produces 3 ATP and 2 ATP respectively. 1 molecule of GTP is equivalent to 1 ATP molecule.

Significance

1. It plays a double significant role in oxidation, as well as in the synthetic process.
2. The citric acid cycle is the final common metabolic pathway in the oxidation of carbohydrates, fats and proteins.

Glycolysis pathway

Glycolysis is an oxidative pathway of carbohydrate metabolism through which 1 molecule of glucose(6 carbon) is converted into 2 molecules of pyruvate(3 carbon), ATP and NADH. It occurs in the cytoplasm of a living cell. Under aerobic condition glucose is converted into pyruvate while under anaerobic condition Glucose is converted into 2 molecules of Lactates and ATP.

    Pyruvate molecules thus produced in the cytoplasm are carried to the mitochondria, where it enters into Linc reaction.

 Linc reaction-

     Acetyl CO-A thus produced, completely oxidized into carbon dioxide through Kreb's cycle.

 In this way, the energy stored in glucose is obtained in the form of small packets called ATP.

   

• Glycos =sugar, Lysis= breakdown
• Also called EMP(Embden, Mayerhof and Parnas) Pathway
•  The first step of the respiratory pathway
• The first step for both aerobic and anaerobic pathway
• Oxygen is not required, hence most appropriately anaerobic pathway
• Enzymes for glycolysis present in the cytoplasm
• Glucose molecule incompletely breakdown to form 2 molecules of pyruvate.
• Along with Pyruvate 2 molecules of NADH also produced.
• 4 molecules of ATP are produced during glycolysis, But 2 molecules of ATP consumed during glycolysis. 
• Hence net gain of 2 molecules of ATP during glycolysis.

Pathway

All the steps in glycolysis pathway can be divided into 3 phases-

1. Energy Investment Phase
2. Splitting Phase
3. Energy generation Phase

Steps of Glycolysis

Step- 1: Conversion of glucose to glucose-6-phosphate

 Glucose is converted into glucose-6-phosphate in the presence of enzyme Hexokinase. Magnesium(mg++), which acts as a prosthetic group, enhances the action of enzyme hexokinase. This step consumes 1 ATP molecule.

Step- 2: Conversion of glucose-6-phosphate to fructose-6-phosphate

This reaction is catalyzed in the presence of enzyme Phosphoglucose Isomerase, which transforms the six-membered ring(glucose-6-phosphate) into a five-membered ring(fructose-6-phosphate).

Step- 3: Conversion of fructose-6-phosphate to fructose-1,6-bisphosphate

Phosphofructokinase is used to catalyze the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate, where magnesium ion acts as a prosthetic group. Phosphofructokinase is also known as the pacemaker of respiration, which is activated by AMP/ADP and inactivated by excess ATP.