Highlights Glycolysis II

1. Glycolysis is a metabolic pathway for the breakdown (catabolism) of glucose and related sugars. The pathway requires two ATPs to start the process and generates 4 ATPS (for a net of two ATPs) per glucose. Also generated during glycolysis are two NADH and two molecules of pyruvate.

2. The two NADHs produced in glycolysis are a factor in determining which pathways is taken after pyruvate is produced in glycolysis. Three different pathways are possible AFTER glycoysis. Pyruvate is the last molecule made in glycolysis.

3. Both animals, plants, and microorganisms have the same pathway when oxygen is available. This involves converting pyrvate into acetyl-CoA for oxidation in the citric acid cycle. When oxygen is present, NADH donates its electrons to the electron transport system, creating NAD+. This means there is plenty of NAD+ when oxygen is abundant.

4. In animals, lactate is made from pyruvate when oxygen is missing (anaerobic - such as in muscles during heavy exertion). This is done to regenerate NAD+, which is low in low oxygen conditions. NAD+ is needed to keep glycolysis going under these conditions.

5. In microorganisms, pyruvate is converted to ethanol during anaerobic conditions for the same reasons lactate is made in animals - because it creates NAD+ needed to keep glycolysis going when oxygen concentration is low.

6. Conversion of pyruvate to ethanol involves two enzymes - 1) pyruvate decarboxylase (requires lipoic acid, NAD+, FAD, coenzyme A, and thiamine pyrophosphate) to convert pyruvate to acetaldehyde and 2) alcohol dehydrogenase to convert acetaldehyde to ethanol. The latter reaction is the one where NADH is used and NAD+ is produced.

7. Pyruvate is the ending point for glycolysis. Which pathway is taken from that point forward depends on the needs of the cell. Since cells have a VERY strong interest in keeping glycolysis going, the primary consideration is keeping NAD+ levels high. Under aerobic conditions (plenty of oxygen), NAD+ is readily made from NADH without problems. Thus under aerobic conditions, cells (animal and microbial cells) convert pyruvate to acetyl-CoA, CO2, and NADH, since the NADH can readily be converted back to NAD+.

8. Metabolism of glucose by anaerobic pathways does not release nearly as much energy as when glucose is metabolism by the aerobic pathway. Note that conversion of pyruvate to ethanol by microorganisms is a two step process. The last step in the process is catalyzed by alcohol dehydrogenase. In microorganisms, the direction of the reaction is towards producing ethanol. Animals also have an alcohol dehydrogenase, but they use it for the reverse direction to break down ethanol. The product of the reverse reaction is acetaldehyde and may be responsible for hangovers.

9. Glycolysis is regulated by three enzymes - hexokinase (inhibited by G6P), phosphofructokinase (inhibited by ATP), and pyruvate kinase (inhibited by ATP).

10. Hexokinase's regulation is not simple and I don't discuss it here. PFK's regulation is allosteric and involves several possible molecules. They include AMP (indicates low cellular energy and stimulates enzyme to be active), F2,6BP (activates PFK strongly in very low concentrations), and ATP (indicates high energy and inhibits the enzymes under high concentrations).

11. Pyruvate kinase is actually regulated by covalent modification (we'll talk about that later) and allosterically. Allosteric activation occurs with either F1,6BP (feedforward activation) or AMP (indicates low cellular energy). Allosteric inhibition occurs with ATP. Inhibition of pyruvate kinase is very important to keep gluconeogenesis going (synthesis of glucose) when it is occurring.