User:Jelly Bean MD/Citric acid cycle

The citric acid cycle, also known as the tricarboxylic (TCA) cycle or the Krebs cycle, consists of a series of biochemical reactions taking place in the mitochondrial matrix. The goal of the TCA cycle is to reduce NAD⁺ to NADH and FAD to FADH₂ in order to synthesize adenosine triphosphate, the cell's main energy currency.

Steps of the TCA cycle

The TCA cycle comprises the following steps:

1. Acetyl-CoA, a two-carbon molecule, enters the cycle and reacts with oxaloacetate, a four-carbon molecule, to form citrate, a six-carbon molecule. This reaction is catalyzed by the enzyme citrate synthase. Coenzyme A is released.
2. Citrate is converted to isocitrate via aconitase.
3. Isocitrate dehydrogenase catalyzes the conversion of isocitrate to alpha-ketoglutarate, a five-carbon molecule. One molecule of carbon dioxide (CO₂) and one molecule of NADH result.
4. Alpha-ketoglutarate is converted to succinyl-CoA, a four-carbon molecule, via the alpha-ketoglutarate dehydrogenase complex. Once again, one molecule of CO₂ and one molecule of NADH result. At this point, the equivalent of the two carbon atoms that were introduced into the cycle as acetyl-CoA have been released as carbon dioxide.
5. Succinyl-CoA synthetase catalyzes the conversion of succinyl-CoA to succinate. The energy in the thioester bond is harvested to form one molecule of guanosine triphosphate (GTP) from guanosine diphosphate (GDP) and inorganic phosphate (P_i) via substrate-level phosphorylation.
6. Succinate is converted to fumarate via the action of the succinate dehydrogenase enzyme. During this step, one molecule of FAD is also reduced to FADH₂.
7. The enzyme fumarase catalyzes the conversion of fumarate to malate.
8. Malate is converted to oxaloacetate via malate dehydrogenase. One molecule of NAD⁺ is reduced to NADH. The equilibrium actually favours the formation of malate; that is, the formation of oxaloacetate is an energetically unfavourable process.

Products of the TCA cycle

Apart from the carbon molecules that are continuously undergoing biochemical conversions in the cycle, each molecule of acetyl-CoA introduced into the TCA cycle yields a total of two molecules of carbon dioxide, one molecule of FADH₂ and three molecules of NADH.

Since one molecule of glucose, following glycolysis, yields two molecules of pyruvate, which are converted to two molecules of acetyl-CoA, for each molecule of glucose oxidized, the total yield in the TCA cycle is four molecules of carbon dioxide, six molecules of NADH, and two molecules of FADH₂.

Mnemonic

A simple mnemonic that is often used by university students to remember the main substrates in the TCA cycle is the following:

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where

O = oxaloacetate, which combines with acetyl-CoA

c = citrate

I = isocitrate

a = alpha-ketoglutarate

s = succinyl-CoA

s = succinate

f = fumarate

m = malate

Enzymes

The above mnemonic can also be used to remember the enzymes involved in the many biochemical reactions in the TCA cycle. One useful observation is that the names of the enzymes follow the names of their substrates. Succinyl-CoA synthetase, for example, converts its substrate, succinyl-CoA, into succinate (with the production of one GTP). This simple rule functions for almost every enzyme, except aconitase, which is responsible for the conversion of citrate into its isomer isocitrate. Finally, one may keep in mind that succinate dehydrogenase catalyzes the conversion of succinate into fumarate and FADH₂. Notice how both products begin with the letter F.

Furthermore, succinate dehydrogenase is an enzyme part of the electron transport chain; more particularly, it is part of complex II, also known as succinate-CoQ reductase.

Reference

Brooker, Robert, Eric Widmaier, Linda Graham, Peter Stiling, Clare Hasenkampf, Fiona Hunter, Michael Bidochka, and Daniel Riggs. Biology. Canadian Edition. United States of America: McGraw-Hill Ryerson, 2010. Print.