Nad

NADH CO2

Figure 13.2. The Krebs cycle.

1. A molecule of acetyl-CoA enters the cycle, and the acetate (two carbons) is combined with the four-carbon molecule oxaloacetate, making citrate (as carboxyl groups are ionized at the pH in the cell, we normally speak of them as ions; so we say "citrate" rather than citric acid).

2. Citrate is rearranged to isocitrate.

3. In the first oxidation step isocitrate is oxidized to 2-oxoglutarate (sometimes called a-ketoglutarate). A carbon is lost as CO2 and NAD+ is reduced to NADH.

4. A second oxidation converts 2-oxoglutarate to succinyl-CoA. A second carbon leaves as CO2 and again NAD+ is reduced to NADH. Note that the product is attached to coenzyme A. This reaction is catalyzed by oxoglutarate dehydrogenase.

5. The bond between succinate and CoA is now broken and the energy released used to drive the phosphorylation of a GDP to GTP. y -phosphate groups can be swapped between nucleotides, so this GTP can be used to regenerate ATP from ADP.

6. Succinate is oxidized to fumarate. The oxidant in this case is flavin adenine dinu-cleotide (FAD) and not NAD+ so an FADH2 is produced. FADH2, the reduced form of FAD, does not carry as much energy as NADH but like NADH is used to drive H+ up its electrochemical gradient out of the mitochondrial matrix (page 265). The enzyme involved is succinate dehydrogenase, which is actually part of the electron transport chain (page 267).

7. Water is added to the double bond in fumarate making malate.

8. Malate is oxidized to oxaloacetate in a reaction catalyzed by malate dehydrogenase. One NAD+ is reduced to NADH. The starting compound oxaloacetate has been regenerated and is ready to accept another acetyl group to start another turn of the cycle.

The reactions of the Krebs cycle can be summarized as

CHsCO-CoA + (3 NAD+ + FAD) + GDP + Pi + 3H2O ^ CoA-H + (3 NADH + FADH2) + GTP + 2CO2 + 3H+

where Pi represents an inorganic phosphate ion.

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