Krebs cycle or Citric acid cycle or TCA cycle

Krebs cycle or Citric acid cycle or TCA cycle:

Two molecules of acetyl CoA formed from link reaction now enter into Krebs cycle. It is named after its discoverer, German Biochemist Sir Hans Adolf Krebs (1937). The enzymes necessary for TCA cycle are found in mitochondrial matrix except succinate dehydrogenase enzyme which is found in mitochondrial inner membrane (Figure 14.7).

TCA cycle starts with condensation of acetyl CoA with oxaloacetate in the presence of water to yield citrate or citric acid. Therefore, it is also known as Citric Acid Cycle (CAC) or Tri Carboxylic Acid (TCA) cycle. It is followed by the action of different enzymes in cyclic manner. During the conversion of succinyl CoA to succinate by the enzyme succinyl CoA synthetase or succinate thiokinase, a molecule of ATP synthesis from substrate without entering the electron transport chain is called substrate level phosphorylation. In animals a molecule of GTP is synthesized from GDP1Pi. In a coupled reaction GTP is converted to GDP with simultaneous synthesis of ATP from ADP+Pi. In three steps (4, 5, 9) in this cycle NAD1 is reduced to NADH⁺ H⁺ and at step 7 (Figure14.8) where FAD is reduced to FADH₂.

The summary of link reaction and Krebs cycle in Mitochondria is

Two molecules of pyruvic acid formed at the end of glycolysis enter into the mitochondrial matrix. Therefore, Krebs cycle is repeated twice for every glucose molecule where two molecules of pyruvic acid produces six molecules of CO_2, eight molecules of NADH + H+, two molecules of FADH₂ and two molecules of ATP.

1. Significance of Krebs cycle:

1.           TCA cycle is to provide energy in the form of ATP for metabolism in plants.

2.           It provides carbon skeleton or raw material for various anabolic processes.

3.           Many intermediates of TCA cycle are further metabolised to produce amino acids, proteins and nucleic acids.

4.           Succinyl CoA is raw material for formation of chlorophylls, cytochrome, phytochrome and other pyrrole substances.

5.           α-ketoglutarate and oxaloacetate undergo reductive amination and produce amino acids.

6.           It acts as metabolic sink which plays a central role in intermediary metabolism.

2. Amphibolic nature

Krebs cycle is primarily a catabolic pathway, but it provides precursors for various biosynthetic pathways there by an anabolic pathway too. Hence, it is called amphibolic pathway. It serves as a pathway for oxidation of carbohydrates, fats and proteins. When fats are respiratory substrate they are first broken down into glycerol and fatty acid. Glycerol is converted into DHAP and acetyl CoA. This acetyl CoA enter into the Krebs cycle. When proteins are the respiratory substrate they are degraded into amino acids by proteases. The amino acids after deamination enter into the Krebs cycle through pyruvic acid or acetyl CoA and it depends upon the structure. So respiratory intermediates form the link between synthesis as well as breakdown. The citric acid cycle is the final common pathway for oxidation of fuel molecules like amino acids, fatty acids and carbohydrates. Therefore, respiratory pathway is an amphibolic pathway (Figure 14.9).