Hans Adolf Kreb - Kreb Cycle or TCA Cycle or Citric Acid Cycle

 



The Kreb cycle was first observed in the tissue of a  Columba. It is present in all eukaryotic and prokaryotic cells. In eukaryotes and prokaryotes cells, it occurs in the matrix of the mitochondria and cytoplasm respectively.


German scientist Hans Adolf Krebs' discovered this cycle in 1937. Adolf Krebs received the Nobel Prize for Physiology or Medicine in 1953 for this metabolism  involved in the oxidative breakdown of carbohydrates.


The Krebs Cycle is the second major step in oxidative phosphorylation  after glycolysis and it takes place in Mitochondrial matrix.The Krebs cycle transfers the energy and formed molecules of  glycolysis  to the electron transport chain to produce ATP. The TCA cycle starts when the pyruvic acids that are formed as the end product of glycolysis, combine with the acetyl coenzyme. This acetyl coenzyme is formed in cell as the result of  metabolism of glucose and fatty acids. Therefore Acetyl coA is the connecting link between glycolysis and the kreb cycle. The complete process of kreb cycle can be understood by the following steps - 


STEP -1 

 The TCA cycle starts when  acetyl coA is condensed with oxaloacetic acid  and water. In this step citric acid is formed.

The reaction is catalysed by the enzyme citrate synthase and a molecule of CoA is released.


STEP -2 

Citric acid  is isomerised into isocitric acids.This isomerisation takes place by the enzyme Aconitase.


STEP -3

Iso citric acid undergoes the decarboxylation in presence of enzyme isocitrate dehydrogenase and forms the α-ketoglutaric acid. During this step, the molecule of NAD+ is reduced into NADH2. 


STEP - 4 

α-ketoglutaric acid is again undergone decarboxylation and form  succinyl-CoA.During this step, the molecule of NAD+ is reduced into NADH2 also.This reaction is catalysed by the enzyme α-ketoglutaric dehydrogenase.


STEP - 5

Succinyl coA is converted into succinic acid in presence of succinic thiokinase enzyme.This step is a substrate level phosphorylation because in this step molecule of guanosine triphosphate or GTP is formed and gives rise to ATP. 


STEP - 6

Succinic acid is converted into fumaric acids in presence of succinic dehydrogenase enzyme. During this step, the molecule of FAD+ is reduced into FADH2.


STEP - 7

Fumaric acid is converted into malic acid in presence of fumarase enzymes by losing one molecule of water.


STEP - 8

Malic acid from oxaloacetic acid for the allowing the cycle to continue  in presence of enzyme malate dehydrogenase .During this step, the molecule of NAD+ is reduced into NADH2.


In TCA cycle

There is a substrate level phosphorylation in which, GTP is converted to GDP that lead thevsynthesis of ATP from ADP.

There are three points in the cycle where NAD+ is reduced to NADH2

There is a one point where FAD+ is reduced to FADH2 . 

it also requires regeneration of NAD+ and FAD+ from NADH and FADH2 respectively.





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