Highlights Citric Acid Cycle

1. The citric acid cycle is inhibited by accumulation of ATP and NADH and is favored by ADP and NAD+. ADP and NAD+ are produced during exercise, whereas ATP and NADH are produced by sitting around. The controls are part of what we refer to as respiratory control (or metabolic control).

2. The citric acid cycle plays roles in catabolism AND anabolism. Many amino acids and fatty acids can be converted into molecules that get oxidized in the citric acid cycle. On the other hand, intermediates in the citric acid cycle can readily be converted to amino acids and/or fatty acids.

3. The most important intermediates for conversion between the citric acid cycle and amino acids are oxaloacetate (aspartic acid) and alpha ketoglutarate (glutamate). In addition, pyruvate (not a citric acid cycle intermediate directly) can be converted easily into alanine. Acetyl-CoA, which is a product of fatty acid oxidation, is used in the citric acid cycle.

4. Malate is an important molecule for shuttling oxaloacetate out of the mitochondrion for its use in gluconeogenesis.

5. The glyoxylate cycle is a cycle found in plants, bacteria, and yeast, but not animals. It overlays the citric acid cycle, using many of its enzymes. Two enzymes are unique to the citric acid cycle. They include isocitrate lyase (breaks isocitrate into succinate and glyoxylate) and malate synthase (add acetyl-CoA to glyoxylate to make malate.

6. Because the glyoxylate bypasses the decarboxylations of the citric acid cycle, it produces two oxaloacetates with each turn of the cycle. This yield one net extra oxaloacetate per turn of the cycle and it can be used to make glucose. Thus, the glyoxylate cycle allows cells to make glucose in net amounts, but animals can't do this.

Highlights Electron Transport/Oxidative Phosphorylation

1. Electron transport occurs in the inner wall of the mitochondrion. The overall process of electron transport involves a multi-step process in which electrons from NADH and FADH2 are transferred, ultimately to oxygen. Reduction of oxygen in this way produces water. Four electrons plus four protons plus one O2 molecule yields two molecules of H2O

2. Electrons pass from one complex to another in the wall of the mitochondrion and as electrons pass through some of the complexes, protons are transported by the complexes from INSIDE the inner membrane to OUTSIDE the inner membrane into the intermembrane space. This has the effect of creating a proton gradient - higher concentration of protons outside the inner membrane than inside of it.

3. The pressure of protons to flow back into the mitochondrion provides a "force" that is used to make ATP. This process is called oxidative phosphorylation (described below).

4. The passage of electrons through complexes in the inner mitochondrial membrane is as follows:

NADH > Complex I > Coenzyme Q (CoQ) > Complex III > Complex IV > Oxygen (forming water)

FADH2 > Complex II > Coenzyme Q > Complex III > Complex IV > Oxygen (forming water)

5. As electrons flow through complexes I, III, and IV, protons are "pumped" out of the mitochondrion.

6. Note that electrons starting with NADH pump more protons that electrons starting with Complex II . This ultimately (in oxidative phosphorylation) results in production of more ATPs per NADH than per FADH2 (actually discussed in the lecture that follows).

7. Passage of electrons occurs as a series of oxidation/reductions. As complexes accept electrons, they are reduced and as complexes lose electrons, they are oxidized.

8. Complexes III and IV contain proteins called cytochromes that participate in passing along electrons. Cytochromes contain heme groups (like hemoglobin) that contain an iron ion. The one exception is that one of the cytochromes in Complex IV contains a copper ion (I didn't say this in class).

9. Oxidative phosphorylation occurs when protons move BACK into the mitochondrion (after being pumped out) through a complex commonly called ATP Synthase or Complex V. ATP Synthase has the mushroom-like shape, as shown in class. This complex ROTATEs as protons pass through it. Rotation of the complex creates ATP as proteins in the 'head' of the mushroom rotate through the L, T, and O states.

10. The L state of the proteins is responsible for binding ADP + Pi. The T state is reponsible for compressing ADP + Pi to make ATP. The O state releases the ATP.