Krebs Cycle – Definition, Steps, Products, Regulation.

What is the krebs cycle?

• The Krebs Cycle is also known as The citric acid cycle or TCA cycle (tricarboxylic acid cycle).
• Krebs Cycle is cellular respiration, where involves a series of chemical reactions that release the stored energy via oxidation of acetyl-CoA. The aerobic organisms perform this TCA cycle.
• The acetyl-CoA is generated from Pyruvate (End product of Glycolysis) by the enzyme Pyruvate dehydrogenase complex and in the presence of coenzymes TPP, NAD, FAD, Lipoate, acetyl CoA.
• In 1937, Hans Adolf Krebs discovered The citric acid cycle, for which he received Nobel Prize for Physiology or Medicine in 1953.
• The total amount of energy yield from the TCA cycle is three NADH, one FADH2, and one GTP. 
• The Krebs cycle occurs in the Mitochondria of eukaryotic cells and in Prokaryotic cells (lacks mitochondria) or bacteria Krebs cycle takes place in the cytosol.

Krebs Cycle Steps with Diagram

1. In the First step, the generated acetyl CoA is combined with the oxaloacetate and forms citrate with the release of acetyl group. The conversation is catalyzed by the enzyme citrate synthase. H2o is involved in this reaction.
2. The citrate first undergoes the dehydration process and forms cis-aconitate then undergoes hydration processes to form isocitrate. The whole reaction is catalyzed by the enzyme aconitase.
3. The isocitrate then undergoes oxidative decarboxylation process and forms α-ketoglutarate with the formation of NADH from NAD. The reaction is catalyzed by the enzyme isocitrate dehydrogenase.
4. The α-ketoglutarate is oxidized by reducing the NAD to NADH and releasing one molecule of CO2. Then it picks up Coenzyme A and converts into an Unstable compound called Succinyl CoA. The reaction is catalyzed by the enzyme α-ketoglutarate dehydrogenase.
5. The Succinyl CoA released the CoA-SH and converted it into Succinate. In this step ADP or GDP is converted into ATP or GTP. The reaction is catalyzed by the enzyme Succinyl CoA synthetase.
6. Succinate is converted into Fumarate with the release to two hydrogen atoms. In this step, FAD is converted into FADH2. The reaction is catalyzed by the enzyme succinate dehydragenase.
7. The Fumarate is converted into Malate with the help of the enzyme Fumarase.
8. The malate is now converted into Oxaloacetate with the release of two hydrogen ion. In this step, NAD is converted into NADH and the reaction is catalyzed by Malate dehydrogensae.

The Overall Krebs cycle equation is;

2 acetyl groups + 6 NAD+ + 2 FAD + 2 ADP + 2 Pi = 4 CO2 + 6 NADH + 6 H+ + 2 FADH2 + 2 ATP

Krebs Cycle Products

The followings are the end product of krebs cycle;

• Two molecules of Carbon dioxide.
• Three NADH, and one FADH.
• One ATP or GTP is produced.

These numbers are for one molecule of Acetyl CoA. If we calculate the Product yield from each glucose which is two Acetyl CoA molecules, then we need to multiply these numbers by 2.

Total ATP yield from TCA Cycle

In TCA cycle the ATP is not directly generated, the ATP is generated through the oxidative

Phosphorylation.

During the oxidative Phosphorylation one NADH generates 2.5 or 3 ATP, one FADH2 generates 1.5 or 2 ATP, and one GTP generates 1 ATP. 

The number of ATP yield from one molecule of acetyl CoA in TCA cycle is 12 and the total yield number will be 24 ATP for two molecules of acetyl CoA. 

So, the total ATP yield will be (3*3)+2+1=12 ATP for one Acetyl CoA. For 2 molecules of acetyl, the total ATP yield will be 2*12=24.

Regulation of Krebs Cycle

• The high ratio of [ATP]/[ADP], [NADH]/[NAD], and [acetyl-CoA]/[CoA] allosterically inhibits the PDH complex. If these ratios are decrease, the allosteric activation of pyruvate oxidation results.
• Increased rate of Calcium ion in mitochondrial matrix activates the pyruvate dehydrogenase complex, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase.
• The Long-chain acetyl CoA and ATP allosterically inhibits the Citrate synthase.
• NADH and ATP inhibits the Isocitrate dehydrogenase.
• NADH and succinyl CoA inhibits the α-ketoglutarate dehydrogenase.
• Oxaloacetate inhibits the succinate dehydrogenase enzyme.
• The citrate blocks citrate synthase.

Difference between glycolysis and krebs cycle

References

• https://pediaa.com/difference-between-krebs-cycle-and-glycolysis/
• https://en.wikipedia.org/wiki/Citric_acid_cycle
• https://www.khanacademy.org/science/biology/cellular-respiration-and-fermentation/pyruvate-oxidation-and-the-citric-acid-cycle/a/the-citric-acid-cycle