Chpt 9-3 The Krebs cycle completes page161 - 166
The Krebs cycle completes the energy-yielding oxidation of organic molecules: a closer look
Glycolysis releases less than a quarter of the chemical energy stored in glucose; most of the energy remains stocked in the two molecules of pyruvate. If molecular oxygen is present, the pyruvate enters the mitochondrion, where the enzymes of the Krebs cycle complete the oxidation of the organic fuel.
Upon entering the mitochondrion, pyruvate is first converted to a compound called acetyl coenzyme A, or acetyl
CoA (FIGURE 9.10). This step, the junction between glycolysis and the Krebs cycle, is accomplished by a multienzyme complex that catalyzes three reactions: Pyruvate’s carboxyl group, which is already fully oxidized and thus has little chemical energy, is removed and given off as a molecule of CO
2
. (This is the first step in respiration where CO
2
is released.) The remaining two-carbon fragment is oxidized to form a compound named acetate (the ionized form of acetic acid). An enzyme transfers the extracted electrons to
NAD
+
, storing energy in the form of NADH. Finally, coenzyme A, a sulfur-containing compound derived from a B vitamin, is attached to the acetate by an unstable bond that makes the acetyl group (the attached acetate) very reactive. The product of this chemical grooming, acetyl CoA, is now ready to feed its acetate into the Krebs cycle for further oxidation.
Fig 9-10.
Conversion of pyruvate to acetyl CoA, the junction between glycolysis and the Krebs cycle. A complex of several enzymes catalyzes the three numbered steps, which are described in the text. The acetyl
CoA will enter the Krebs cycle. The CO
2
molecule will diffuse out of the cell.
The Krebs cycle is named after Hans Krebs, the German-British scientist who was largely responsible for elucidating the pathway in the 1930s. The cycle has eight steps, each catalyzed by a specific enzyme (FIGURE
9.11). You can see in the diagram that for each turn of the Krebs cycle, two carbons enter in the relatively reduced form of acetate (step 1), and two different carbons leave in the completely oxidized form of CO
2
(steps 3 and 4). The acetate joins the cycle by its enzymatic addition to the compound oxaloacetate, forming citrate.
Subsequent steps decompose the citrate back to oxaloacetate, giving off CO
2
as "exhaust." It is this regeneration of oxaloacetate that accounts for the "cycle" in the Krebs cycle. Except for the enzyme that catalyzes step 6, which resides in the inner mitochondrial membrane, all the Krebs cycle enzymes are located in the mitochondrial matrix.

Fig 9-11.
A closer look at the Krebs cycle. In the chemical structures, red type traces the fate of the two carbon atoms that enter the cycle via acetyl CoA (step 1), and blue type indicates the two carbons that exit the cycle as
CO
2
in steps 3 and 4. Notice that carboxylic acids are represented in their ionized forms, as --COO
-
. For example, citrate is the ionized form of citric acid.

Most of the energy harvested by the oxidative steps of the cycle is conserved in NADH. For each acetate that enters the cycle, three molecules of NAD
+
are reduced to NADH (steps 3, 4, and 8). In one oxidative reaction, step 6, electrons are transferred not to NAD
+
, but to a different electron acceptor, FAD (flavin adenine dinucleotide, derived from riboflavin, a B vitamin). The reduced form, FADH
2
, donates its electrons to the electron transport chain, as does NADH. There is also a step in the Krebs cycle, step 5, that forms an ATP molecule directly by substrate-level phosphorylation, similar to the ATP-generating steps of glycolysis. But most of the ATP output of respiration results from oxidative phosphorylation, when the NADH and FADH
2
produced by the Krebs cycle relay the electrons extracted from food to the electron transport chain. Use FIGURE 9.12, page 166, to review the inputs and outputs of the Krebs cycle before proceeding to the electron transport chain.
Fig 9-12.
A summary of the Krebs cycle. The cycle functions as a metabolic furnace that oxidizes organic fuel derived from pyruvate, the product of glycolysis. This diagram summarizes the inputs and outputs as pyruvate is broken down to three molecules of CO
2
, and it includes the molecule of CO
2
released during pre-Krebs cycle conversion of pyruvate to acetyl CoA. The cycle generates 1 ATP per turn by substrate phosphorylation, but most of the chemical energy is transferred during the redox reactions to NAD
+
and FAD. The reduced coenzymes, NADH and FADH
2
, shuttle their cargo of high-energy electrons to the electron transport chain, which uses the energy to synthesize ATP by oxidative phosphorylation. (To calculate the inputs and outputs on a "per-glucose" basis, multiply by 2, because each glucose molecule is split during glycolysis into two pyruvate molecules.)