TCA Cycle

The TCA cycle is part of the larger glucose metabolism, where glucose is oxidised to pyruvate and then oxidised into the TCA cycle as acetyl-CoA.This cycle utilises the available chemical energy of acetyl coenzyme A (acetyl-CoA) for the reducing power of nicotinamide adenine dinucleotide (NADH).This metabolic method happens in maximum plants, animals, fungi, and plenty of micro organism. In all organisms besides micro organisms the TCA cycle is completed withinside the matrix of intracellular systems referred to as mitochondria.

Introduction

The citric acid cycle (CAC) — also known as the TCA cycle is a series that releases the stored energy through the oxidation of acetyl-CoA derived from carbohydrates. It is a chemical reaction. Fat, and protein. The Krebs cycle is used by living organisms that breathe (not fermenting organisms) to generate energy through either  anaerobic  or aerobic respiration. In addition, this cycle supplies the precursor of certain amino acids and the reducing agent NADH.

Its central importance in many biochemical pathways suggests that it is one of the earliest components of metabolism and may have originated from abiogenic origin. Called a “cycle,” metabolites do not have to follow  one particular pathway. At least three alternative segments of the citric acid cycle have been identified.

Intermediates of TCA Cycle:

 These intermediates are numbered 

1. Citrate in the figure. 
2. Isocitric acid salt 
3. Oxoglutaric acid 
4. Succinyl CoA 
5. Succinate 
6. Fumarate 
7. Malate 
8. Oxaloacetic acid (oxaloacetic acid)

History of the TCA Cycle:

The discovery of this cycle by German chemist Hans Adolf Krebs in 1937 was a milestone in biochemistry. Krebs was awarded the Nobel Prize in Physiology or Medicine in 1953 for his contribution to the study of intermediate metabolism in the oxidative breakdown of carbohydrates. After rejection in nature, Krebs and his co-author William Arthur Johnson published their findings in Enzymologia, “The Role of Citric Acid in Intermediate Metabolism in Animal Tissues.” This original publication was followed by many others.

Steps involved in Krebs cycle:

It takes place over eight different steps: 

Step 1: Two carbon molecules of acetyl CoA  join with 4 carbon molecule oxaloacetate to form a citrate of 6 carbon molecules.  

Step 2: Citrate is then converted into isocitrate (i.e. an isomer of citrate) 

Step 3: Isocitrate is oxidised to alpha ketoglutarate (a five carbon molecule) which results in the release of carbon dioxide. One NADH molecule is formed.  

The enzyme which is responsible for catalysing this step is isocitrate dehydrogenase. This is a rate reducing step, as isocitrate dehydrogenase is an allosterically controlled enzyme. 

Step 4: Alpha ketoglutarate is oxidised to form  4 carbon molecules. It binds to coenzyme  A and forms succinyl-CoA. In addition to the second molecule of carbon dioxide, the second molecule of NADH is formed. 

Step 5: Next, succinyl-CoA is  converted to succinate (4 carbon molecules) to produce GTP molecules.

Step 6: Succinate is converted to fumarate (4 carbon molecules) and 1 molecule FADH & sub2 ; was produced.

Step 7: Fumarate is converted to malate which is another 4-carbon molecule.

Step 8: Malic acid is then converted to oxaloacetate. The third molecule  NADH is also produced.

The main role of the TCA cycle is to produce NADH and FADH2, but it also produces molecules that supply various biosynthetic processes. The enter or exit of the cycle at different points depends on demand. For example, alpha-keto-glutarate can leave the cycle for conversion into amino acids, and succinate can be converted to haem.

Clean output of Krebs cycle:

Each cycle produces: 

• Two molecules of carbon dioxide.
• Three molecules of NADH.
• 3 hydrogen ions (H+).
• 1 FADH₂ molecule 
•  1 molecule of GTP.

Each glucose molecule  produces two molecules of pyruvic acid, which in turn produce two molecules of acetyl-CoA. Therefore, each molecule of glucose produces double the net output of each cycle.

TCA cycle adjustment:

The TCA cycle is tuned in several ways. 

• Metabolites: The products of the cycle provide negative feedback to the enzymes that catalyze them. For example, NADH inhibits most of the enzymes found in the TCA cycle. 
• Citrate: Inhibits phosphofructokinase, an important glycolytic enzyme. This slows down the  production of pyruvate, and thus acetyl-CoA. 
• Calcium: Speeds up the TCA cycle by stimulating the link response.

Conclusion

The TCA cycle is of particular interest to researchers in the field of metabolism. By studying  rates, byproducts, enzyme activity, and other qualities  of metabolism, researchers can draw conclusions about diseases and study the effectiveness of therapies. These TCA-associated metabolic programs are normally studied the use of solid isotope-classified compounds and mass spectrometry: 

• Lipid Metabolism
• Amino Acid Metabolism
• Protein Metabolism (Turnover)
• Glucose Metabolism
• Energy Expenditure
• Metabolomics