Glycolysis and PDC

What is the purpose of glycolysis and where does it occur in the cell?

Glycolysis breaks down glucose to produce energy in the form of ATP and occurs in the cytoplasm of the cell.

What is the overall balanced equation for glycolysis?

The overall reaction for glycolysis is: $C_6H_{12}O_6 + 2 NAD^+ + 2 ADP + 2 P_i \rightarrow 2 C_3H_4O_3 + 2 NADH + 2 ATP + 2 H_2O$.

What are the three regulated steps in glycolysis, and which enzymes catalyze them?

1. Glucose to Glucose-6-phosphate (catalyzed by Hexokinase)
2. Fructose-6-phosphate to Fructose-1,6-bisphosphate (catalyzed by Phosphofructokinase-1)
3. Phosphoenolpyruvate to Pyruvate (catalyzed by Pyruvate Kinase).

In glycolysis, identify the reactions where ATP is used and generated, substrate-level phosphorylations, oxidation reactions, and regulated steps.

• ATP used: 1. Glucose to Glucose-6-phosphate
• ATP generated: 1. 1,3-Bisphosphoglycerate to 3-Phosphoglycerate
  2. Phosphoenolpyruvate to Pyruvate
• Substrate-level phosphorylations: 1,3-Bisphosphoglycerate to 3-Phosphoglycerate and Phosphoenolpyruvate to Pyruvate
• Oxidation reaction: Glyceraldehyde-3-phosphate to 1,3-Bisphosphoglycerate
• Regulated steps: 1. Glucose to Glucose-6-phosphate, Fructose-6-phosphate to Fructose-1,6-bisphosphate, and Phosphoenolpyruvate to Pyruvate.

What are examples of feedback inhibition, feed-forward activation, and product inhibition in glycolysis?

• Feedback inhibition: ATP inhibiting Phosphofructokinase-1.
• Feed-forward activation: Fructose-2,6-bisphosphate stimulating Phosphofructokinase-1.
• Product inhibition: ATP inhibiting the activity of Pyruvate Kinase.

What are high-energy intermediates in glycolysis and why are they termed 'high-energy'?

High-energy intermediates include 1,3-Bisphosphoglycerate and Phosphoenolpyruvate because their hydrolysis releases a significant amount of energy used to synthesize ATP.

How are hexokinase, PFK-1, and pyruvate kinase regulated?

Hexokinase is regulated by feedback inhibition from glucose-6-phosphate, PFK-1 is activated by AMP and inhibited by ATP and citrate, and Pyruvate Kinase is activated by fructose-1,6-bisphosphate and inhibited by ATP and acetyl-CoA.

Why is ADP an allosteric activator of certain glycolytic enzymes?

ADP indicates low energy levels in the cell, so its activation of glycolytic enzymes promotes ATP production when energy is needed.

Why is the gross yield of ATP from glycolysis 4 molecules but the net yield is only 2?

The gross yield is 4 ATP but 2 ATP are consumed in the early steps, resulting in a net yield of 2 ATP.

Explain the significance of oxidation reactions in glycolysis for energy capture. How does it differ under aerobic and anaerobic conditions?

Under aerobic conditions, NADH produced can be oxidized in the electron transport chain yielding more ATP. Under anaerobic conditions, NADH is converted back to NAD+ allowing glycolysis to continue, but only 2 ATP are generated.

Why does glycogen produce a net yield of 3 ATP from glycolysis?

Glycogen is broken down to glucose-1-phosphate, which can enter glycolysis directly at a step that does not require ATP, leading to one additional net ATP compared to glucose.

What are three immediate metabolic fates of pyruvate, and are they aerobic or anaerobic?

1. Conversion to Acetyl-CoA (aerobic)
2. Conversion to Lactate (anaerobic)
3. Conversion to Ethanol (anaerobic).

Explain the reasons for anaerobic fates of pyruvate. What happens in anaerobic muscle?

Anaerobic fates allow glycolysis to continue producing ATP when oxygen is low. In anaerobic muscle, pyruvate is converted to lactate, represented by the equation: $C_3H_4O_3 + NADH \rightarrow C_3H_6O_3 + NAD^+$.

Why is lactate considered a 'dead-end' product in skeletal muscle?

Lactate must be reconverted back to glucose in the liver through gluconeogenesis, consuming energy; hence, it's not directly usable as an energy source in skeletal muscle.

How is lactate transported into the bloodstream from muscle cells and what is the metabolic advantage?

Lactate is transported from muscle cells into the bloodstream via monocarboxylate transporters, allowing muscle cells to recycle lactate back into glucose in the liver while reducing acidosis.

Explain how lactate can be used as a metabolic fuel under aerobic conditions.

Under aerobic conditions, lactate can be converted back to pyruvate and utilized in the Krebs cycle for ATP production.

Identify the source of H+ ions causing acidotic damage to muscle fibers during vigorous exercise.

The source of H+ ions is the production of lactic acid from lactate during anaerobic respiration, which decreases pH and causes acidosis.

Outline the route by which pyruvate moves from the cytoplasm into the mitochondrial matrix.

Pyruvate moves into the mitochondrial matrix through specific transport proteins known as pyruvate carriers.

Sketch a simple structural representation of acetyl-CoA.

Acetyl-CoA consists of an acetyl group (C2H3O) linked to coenzyme A, represented as: $CH_3C(=O)SCoA$.

Why is acetyl-CoA called a 'high-energy' intermediate?

Acetyl-CoA is termed 'high-energy' because it contains a thioester bond, which, when hydrolyzed, releases significant energy used in various metabolic pathways.

Write a balanced equation for the reaction catalyzed by pyruvate dehydrogenase.

The reaction is: $C_3H_4O_3 + NAD^+ + CoA \rightarrow C_2H_3O + CO_2 + NADH + H^+$.

What are two advantages of multi-enzyme complexes?

1. Increased efficiency as substrates are channeled from one enzyme to the next without diffusion.
2. Regulation of multiple steps in metabolic pathways by controlling the entire complex.

Why is the activity of pyruvate dehydrogenase tightly regulated?

The activity of PDH is tightly regulated to balance energy production and substrate availability, ensuring appropriate responses to cellular energy demands.

How do NADH, NAD+, ADP, pyruvate, acetyl-CoA, and Ca2+ ions regulate PDH activity?

• NADH inhibits PDH, indicating high energy.
• NAD+ activates PDH, signaling low energy.
• ADP activates PDH, promoting energy production.
• Pyruvate is a substrate activating PDH.
• Acetyl-CoA inhibits PDH, indicating sufficient energy storage.
• Ca2+ activates PDH, stimulating energy production during muscle contraction.