Citric acid cycle

History and overview of citric acid cycle

o The tricarboxylic acid (TCA) cycle was first correctly formulated by

Sir Hans Adolf Krebs, German-born British biochemist who received

the 1953 Nobel Prize for Physiology or Medicine for the discovery in

living organisms of the series of chemical reactions known as the citric

acid cycle, or Krebs cycle.

o It is the major energy-yielding metabolic pathway in cells.

o It is the second stage of cellular respiration. It plays a central role in the

breakdown of organic fuel molecules—i.e., glucose and some other

sugars, fatty acids, and some amino acids.

o A substantial portion of acetyl-CoA comes from glucose or more

specifically, pyruvate catalyzed by the pyruvate dehydrogenase

complex (PDC).

Fig: Oxidation of pyruvate

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 Citric acid cycle

o Once fed into the TCA cycle, acetyl CoA is converted into carbon

dioxide and energy.

o In this process, the greater part of the reduced coenzymes that will be

oxidized by the electron transport chain to yield ATP.

o This metabolic process occurs in most plants, animals, fungi, and many

bacteria.

o In all organisms except bacteria the TCA cycle is carried out in the

matrix of intracellular structures called mitochondria.

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Citric acid cycle

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o Steps of the citric acid cycle

Step 1: Acetyl CoA combines with oxaloacetate in a reaction catalyzed by citrate

synthase. This reaction also takes a water molecule as a reactant, and it releases a

SH-CoA molecule as a product.

Step 2: Citrate is converted into its isomer, isocitrate in a reaction catalyzed by

aconitase. This is actually a two-step process, involving first the removal and then

the addition of a water molecule.

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 Citric acid cycle

Step 3. In this reaction, isocitrate is oxidized and releases a molecule of carbon

dioxide, leaving behind a five-carbon molecule—α-ketoglutarate catalyzed by

isocitrate dehydrogenase. During this step, NAD+ is reduced to form NADH.

Step 4: α-ketoglutarate is converted to succinyl CoA in a reaction catalyzed by α-

ketoglutarate dehydrogenase. An NAD+ molecule is reduced to NADH + H+ in

this reaction, which also takes a SH-CoA molecule as reactant. A CO 2 molecule is

released as a product.

Step 5: Succinyl CoA is then converted to succinate (four-carbon molecule) and

one ATP molecule is produced. This reaction catalyzed by succinyl-CoA

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 Citric acid cycle

synthetase. In some cells, GDP (guanosine diphosphate) is used instead of ADP,

forming GTP as a product.

Step 6: Succinate is oxidized, forming fumarate in a reaction catalyzed by

succinate dehydrogenase. In this reaction, two hydrogen atoms—with their

electrons—are transferred to FAD, producing FADH2.

Step 7: Water is added to the four-carbon molecule fumarate, converting it into

malate in a reaction catalyzed by fumarase.

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 Citric acid cycle

Step 8. In the last step, oxaloacetate is regenerated by the oxidation of malate by

malate dehydrogenase. Another molecule of NAD+ is reduced to NADH in the

process.

Products of the citric acid cycle

In a single turn of the cycle,

 two carbons enter from acetyl CoA, and two molecules of carbon dioxide are
released

 three molecules of NADH and one molecule of FADH2 are generated; and

 one molecule of ATP or GTP is produced

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 Citric acid cycle

Amphibolic nature of TCA Cycle:

It is the second stage of cellular respiration by which living cells break down

organic fuel in the presence of oxygen to produce the energy for their growth.

It takes place inside the mitochondria of the cell in all organisms except in

bacteria.

An amphibolic pathway is a biochemical pathway that includes both anabolic

as well as catabolic reactions. TCA cycle is called an amphibolic (double

way) cycle because energy is both consumed and produced during this

process.

Catabolic part of Krebs cycle:

During the catabolic (energy production) part of the cycle acetyl CoA

is converted to produce CO2, and energy, which is later used to produce

FADH and NADH.

Anabolic reaction of Krebs cycle:

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 Citric acid cycle

During the anabolic (energy consuming) part of the cycle several

intermediates of this pathway are converted to Succinyl CoA to Succinic acid

using ATP.

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Citric acid cycle

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