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  • The citric acid cycle is a series of chemical

  • reactions that takes place in the mitochondrial matrix.

  • This cycle uses acetyl CoA

  • derived from sugar and fat breakdown

  • to form ATP, NADH, FADH2, and carbon dioxide.

  • The NADH and FADH2

  • can be used to form additional ATP

  • through the electron transport chain.

  • The citric acid cycle goes by many names

  • including the tricarboxylic acid (or TCA) cycle

  • and the Krebs cycle.

  • Citric acid refers to the citrate that is produced in the first step of the pathway.

  • The tricarboxylic acid title gets its name

  • from the three carbon dioxides that are produced

  • for each fully oxidized pyruvate.

  • Krebs refers to Hans Adolf Krebs

  • who identified the full cycle in 1937.

  • He was eventually awarded the Nobel Prize for

  • Physiology or Medicine in 1953 for his discovery.

  • In the first step of the cycle,

  • an enzyme called citrate synthase

  • joins the two-carbon acetyl group from acetyl CoA

  • with the four-carbon oxaloacetate

  • to form a six-carbon citrate.

  • In step two, an enzyme called aconitase

  • converts citrate into isocitrate.

  • Next, an isocitrate dehydrogenase enzyme

  • oxidizes isocitrate, a six-carbon molecule,

  • to a five-carbon α-ketoglutarate.

  • The carbon that was lost is released as carbon dioxide

  • and one NADH is also formed.

  • The carbon dioxide that is released

  • was originally part of oxaloacetate

  • and not acetyl CoA.

  • In the fouth step,

  • an enzyme called α-ketoglutarate dehydrogenase

  • converts α-ketoglutarate

  • into a four-carbon succinyl CoA.

  • Similar to step three,

  • this reaction produces one carbon dioxide

  • and one NADH.

  • In step five,

  • a succinyl CoA synthetase enzyme

  • converts succinyl CoA into succinate.

  • This produces GTP which is converted to ATP.

  • In step six,

  • an enzyme called succinate dehydrogenase

  • converts succinate into fumarate.

  • This step makes one FADH2.

  • In step seven, a fumarate hydratase enzyme

  • then converts fumarate into malate.

  • In the final step of the citric acid cycle,

  • a malate dehydrogenase enzyme

  • converts malate back to oxaloacetate.

  • Like all steps involving a dehydrogenase,

  • a coenzyme is produced.

  • Here it is NADH.

  • The oxaloacetate that was regenerated through the citric acid cycle

  • is now ready to join with another acetyl group

  • and begin the cycle a second time.

  • For every one glucose that is broken down through glycolysis,

  • two pyruvates will be produced.

  • These two pyruvates will produce two acetyl CoAs.

  • So, for every one glucose,

  • two acetyl CoAs will be made

  • and two turns of the citric acid cycle will occur.

  • This means each product of the cycle must be doubled.

  • A total of four CO2,

  • six NADH,

  • two FADH2, and two ATPs are made

  • through the citric acid cycle.

  • NADH and FADH2 are electron carriers

  • that can produce more ATPs later in aerobic respiration.

  • In addition to sugars like glucose,

  • proteins and fats can also provide carbon substrates to fuel the citric acid cycle.

  • Proteins can be broken down into individual amino acids

  • such as alanine, aspartate, and glutamate

  • and converted into intermediates in the cycle.

  • Fatty acids can be broken down into acetyl CoA

  • which then begins the citric acid cycle.

  • This metabolism of sugars, proteins, and fats

  • through the citric acid cycle

  • provides the vital energy necessary to maintain many cellular processes.

The citric acid cycle is a series of chemical

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