Intermediates of TCA Cycle

Hans Kreb’s developed the citric acid cycle, also known as the tricarboxylic acid (TCA) cycle, in 1937 and was awarded the Nobel Prize in Physiology or Medicine in 1953 for his discovery.

The TCA cycle is an eight-step process that aids in the decomposition of organic compounds. Glucose, sugars, fatty acids, amino acids, and other macromolecules cannot enter the TCA cycle directly. As a result, they are initially decomposed into the two-carbon molecule Acetyl CoA.

TCA Cycle 

The tricarboxylic acid (TCA) cycle, known as the Krebs or citric acid cycle, is the primary source of energy for cells and a crucial component of aerobic respiration. 

The cycle converts the available chemical energy of acetyl coenzyme A (acet commonly yl CoA) into the nicotinamide adenine dinucleotide’s reducing power (NADH). 

Most plants, animals, fungi, and bacteria go through this metabolic process. The TCA cycle is carried out in the matrix of internal organelles called mitochondria in all organisms except bacteria.

The citric acid cycle has the following overall reaction: acetyl-CoA + 3 NAD+ + FAD + GDP + P + 2H2O = CoA-SH + 3NADH + FADH2 + 3H+ + GTP + 2CO2. Many of the chemicals in the citric acid cycle are important precursors for other compounds that cells require.

Role of TCA Cycle

The TCA cycle is involved in the breakdown, or catabolism, of organic fuel molecules such as glucose and other sugars, fatty acids, and some amino acids. These relatively big molecules must be reduced into acetyl coenzyme A, a two-carbon chemical before they can join the TCA cycle (acetyl CoA). Acetyl CoA is transformed into carbon dioxide and energy after being supplied into the TCA cycle.

Regulation of TCA cycle

The TCA Cycle is influenced by several factors, including:

Metabolites: The cycle’s products act as a negative feedback loop on the enzymes that catalyse it. The bulk of the enzymes in the TCA cycle, for example, are inhibited by NADH.

Citrate inhibits the enzyme phosphofructokinase, which is involved in glycolysis. This slows the formation of pyruvate and, as a result, acetyl-CoA.

Calcium stimulates the link reaction, which speeds up the TCA cycle.

Importance of TCA Cycle

The Krebs cycle is the second of three stages of cellular respiration, in which the so-called fuel molecules glucose, fatty acids, and some amino acids are oxidised (see Figure). 

The energy contained in these molecules is converted into ATP through the oxidation of these molecules. ATP is the “energy currency” of the cells since it supplies energy for muscular contractions, for example.

All of the fuel molecules must first be transformed to acetyl-CoA before they can be put into the Krebs Cycle. When a nutrient, such as glucose, travels through the body, it undergoes glycolysis, which involves the oxidation of the molecule. Pyruvate is the end product of glycolysis.

Working on TCA Cycle

The cycle converts the available chemical energy of acetyl coenzyme A (acetyl CoA) into the nicotinamide adenine dinucleotide’s reducing power (NADH). The TCA cycle is a part of the wider glucose metabolism, in which glucose is oxidised to generate pyruvate, which is subsequently oxidised to form acetyl-CoA, which enters the TCA cycle as acetyl-CoA.

Kreb Cycle Enzymes

Except for succinate dehydrogenase and aconitase, which are found in the inner mitochondrial membrane of eukaryotic cells, the enzymes that catalyse the processes of the citric acid cycle are found in the matrix of the mitochondria in eukaryotic cells.

• Nearly all of the enzymes involved in the citric acid cycle require Mg2+.
• Enzymes that catalyse distinct phases in the citric acid cycle are as follows:
• Citrate synthase is an enzyme that produces citrate.
• Aconitase Isocitrate dehydrogenase is an enzyme that dehydrates isocitrate.

Α-ketoglutarate

• CoA synthetase is a type of enzyme that produces succinyl-CoA.
• Succinate dehydrogenase is an enzyme that dehydrates succinate.

Fumarase

• Malate dehydrogenase is a type of malate dehydrogenase enzyme. 

Significance of TCA Cycle

1. Amino acids, nucleotides, chlorophyll, cytochromes, and lipids, among other biomolecules, are synthesised from intermediate chemicals generated during the Krebs cycle. 
2. Succinyl CoA, an intermediate, is involved in the formation of chlorophyll.
3. Ketoglutaric acid, pyruvic acid, and oxaloacetic acid combine to form amino acids.
4. The Krebs cycle generates enough energy for the cell’s various metabolic activities. 
5. This cycle produces a carbon skeleton, which is used in the growth and maintenance of cells.

Conclusion:-

Citric acid permits organisms to transport electrons from pyruvate and other Acetyl-COA precursors to the mitochondrial electron transport chain. When pyruvate is converted to Acetol- COA, one NADH is produced. The citric acid cycle produces three NADH, one FADH, and one GTP/ATP, as well as precursors for other compounds. The citric acid cycle is regulated by NADH, and ultimately by oxygen supply, and intermediates can be generated from pyruvate and amino acids to boost flow through or replace those utilised in biosynthesis.