27. Ahern's BB 350 at Oregon State University - Glycolysis II & Gluconeogenesis

Highlights Glycolysis II

1. In reaction 8, 3-PG is converted to 2-PG, catalyzed by phosphoglycerate mutase. An intermediate in the reaction is 2,3 BPG

2. In reaction 9, 2-PG is converted to PEP, catalyzed by enolase.

3. Reaction 10 is the "Big Bang" of glycolysis. In it, PEP is converted to pyruvate and an ATP is made by substrate level phosphorylation.

4. Glycolysis is regulated allosterically by three enzymes - hexokinase (inhibited by G6P), phosphofructokinase (inhibited by ATP, activated by AMP, F2,6BP), and pyruvate kinase (inhibited by ATP). These largely are related to energy considerations - high energy indicator (ATP) stops pathway. Low energy indicator (AMP) activates pathway.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

Highlights Gluconeogenesis

1. Gluconeogenesis is the pathway that is involved in the synthesis of glucose. It operates mostly in the liver and kidney. It uses 7 of the same enzymes as glycolysis by running the reactions in the opposite direction from glycolysis. The other three enzymes are replaced by four new enzymes in gluconeogenesis. The two of these are pyruvate carboxylase and phosphoenolpyruvate carboxykinase (PEPCK).

2. Pyruvate carboxylase is a biotin-containing enzyme that is found in the mitochondrion and it catalyzes the addition of a carboxyl group to pyruvate to make oxaloacetate. The reaction requires ATP

3. In the cytoplasm, PEPCK catalyzes the conversion of oxaloacetate to PEP and the reaction requires GTP. The next reactions for gluconeogenesis are the reversal of reactions of glycolysis up to PFK.

4. The PFK enzymatic reaction of glycolysis is replaced by the enzyme fructose-1,6bisphosphatase (F1,6BPase). It acts to remove a phosphate from F1,6BP, yielding F6P. This reaction is energetically favorable, since ATP is NOT regenerated (as it would be if the glycolysis reaction were reversed).

5. The hexokinase reaction of glycolysis is replaced by the enzyme glucose-6-phosphatase (G6Pase), which acts to remove a phosphate from G6P to yield free glucose. This reaction is energetically favorable, since ATP is NOT regenerated (as it would be if the glycolysis reaction were reversed).

6. Reciprocal regulation of glycolysis and gluconeogenesis is accomplished mainly by the molecule fructose-2,6-bisphosphate (F2,6BP). It acts to stimulate glycolysis by turning on PFK (your book calls it PFK-1) while at the same time acting to inhibit gluconeogenesis by turning off the corresponding enzyme, F1,6BPase. Thus, when F2,6BP is present, glycolysis is running and gluconeogenesis is inhibited. When F2,6BP is absent, gluconeogenesis is running and glycolysis is inhibited

[romeocandelma]

Since you said the Big Bang reaction produces a lot of energy and is the reason you get hot while running, if someone has low metabolism, does that mean they possibly get less hot while running than someone who has high metabolism? And they will sweat less?