Lecture 2 - Fate of Pyruvate Flashcards
What determines the fate of pyruvate?
- Presence/absence of oxygen
- Type of organism
What can pyruvate be converted into?
- Ethanol
- Lactate
- Acetyl-CoA
Where is pyruvate converted into lactate?
Muscle
What converts pyruvate into ethanol?
Yeast
Why is pyruvate anaerobically metabolized?
To reoxidize NADH to NAD+ to keep glycolysis going
Where and under what conditions is lactate converted to pyruvate?
- In the heart
- During high oxygen periods
What is released during fermentation?
CO2
Which enzyme converts pyruvate to lactate?
Lactate dehydrogenase
Which enzyme converts lactate to pyruvate?
Lactate dehydrogenase
What is the cofactor in the conversion of pyruvate to lactate?
NADH + H+ -> NAD+
Which enzyme converts pyruvate to acetaldehyde?
Pyruvate decarboxylase
Which enzyme converts acetaldehyde to ethanol?
Alcohol dehydrogenase
Which enzyme converts ethanol to acetaldehyde?
Alcohol dehydrogenase
What is the cofactor in the conversion of pyruvate to acetaldehyde?
CO2 lost
What is the cofactor in the conversion of acetaldehyde to ethanol?
NADH + H+ -> NAD+
_____ accumulation causes a hangover
Acetaldehyde
Which enzyme converts acetaldehyde to acetate?
Acetaldehyde dehydrogenase
What is the cofactor in the conversion of acetaldehyde to acetate?
NAD+ -> NADH + H+
Where does the conversion of acetaldehyde to acetate occur?
In the liver
Which enzymes catalyzes the conversion of acetate to acetyl CoA?
Acetyl-CoA synthetase
What is the cofactor in the conversion of acetate to acetyl-CoA?
ATP -> AMP + PPi
How many ATP molecules can be produced from one ethanol molecule? Describe where each is produced/used
- 2 NADH produced from the conversions of ethanol and acetaldehyde, which is equivalent to 5 ATP
- 2 ATP used for the production of acetyl-CoA
- Total of 3 ATP produced
How can you physically tell that someone has acetaldehyde accumulation?
Red cheeks
Which enzyme catalyzes the conversion of pyruvate to acetyl-CoA?
Pyruvate dehydrogenase complex
What are the cofactors in the conversion of pyruvate to acetyl-CoA?
- CoA-SH in
- NAD+ -> NADH
- TPP, lipoate, FAD
What are the 3 enzymes that make up pyruvate dehydrogenase?
1) Pyruvate decarboxylase
2) Dihydrolipoate transacetylase
3) Dihydrolipoate dehydrogenase
What does pyruvate decarboxylase use?
TPP
What does dihydrolipoate transacetylase use?
Lipoic acid
What is the function of dihydrolipoate dehydrogenase?
NADH-FADH2 oxidoreductase
Which vitamins are required for pyruvate dehydrogenase and why?
- Riboflavin (B2) for FAD
- Niacin (B3) for NAD
- Panthothenate (B5) for CoA
- Thiamine (B1) for TPP
Where does the conversion of pyruvate to acetyl-CoA occur?
- Mitochondria in eukaryotes
- Cytosol in bacteria
How can pyruvate dehydrogenase be inactivated?
NADH (a high energy signal) activates protein kinase, which converts pyruvate dehydrogenase to an inactive form
How many subunits does pyruvate dehydrogenase have?
12
How can pyruvate dehydrogenase be activated?
By protein phosphatase
What are the cofactors required for pyruvate dehydrogenase and in which complex do they work?
1) Thiamine pyrophosphate (TPP) in E1
2) Lipoic acid in E2
3) Flavian adenine dinucleotide (FAD) in E3
4) NAD and CoA
What is NAD short for?
Nicotinaminde adenine dinucleotide
What is the active portion of TPP called?
Thiazolium ring
Where is a thiazolium ring found besides TPP?
- Alpha-ketoglutarate dehydrogenase
- Isovalerate dehydrogenase
What does lipoate act as?
An acyl carrier and an electron carrier
What is the first step of pyruvate dehydrogenase and what can be the attacker in this step?
- The attack of the TPP carbanion, followed by the release of CO2
- Either pyruvate dehydrogenase or pyruvate decarboxylase
Where is pyruvate dehydrogenase used?
In mitochondria
Where is pyruvate decarboxylase used?
Yeast fermentation
What is the product of the first step of pyruvate dehydrogenase?
- Acetaldehyde if the attacker is pyruvate decarboxylase
- Acetyl-CoA if the attacker is pyruvate dehydrogenase
How is lipoic acid converted back to its original form in pyruvate dehydrogenase?
FAD and NAD+ (eventually) act as electron acceptors
What would happen to pyruvate dehydrogenase if lipoic acid wasn’t present?
Acetaldehyde would be produced
Does the pyruvate dehydrogenase or pyruvate decarboxylase reaction use TPP?
Both
What happens in the second step of the pyruvate dehydrogenase mechanism?
Transfer of 2 electrons and acetyl group to lipoate
What happens in the third step of the pyruvate dehydrogenase mechanism?
Transesterification
What happens in the fourth step of the pyruvate dehydrogenase mechanism?
2 electrons are transferred to FAD from dihydrolipoate (E3)
What happens in the fifth step of the pyruvate dehydrogenase mechanism?
Oxidation of FADH2 from E3 by NAD+
