Ch. 14 Flashcards
What is the pentose phosphate pathway (PPP)?
Metabolic pathway in which glucose-6-P is oxidized then decarboxylated, generating ribulose-5-P and NADPH
Where does the PPP occur?
In the cytoplasm
What are the important functions of the PPP?
- Reduce 2 molecules of NADP+ to NADPH for each molecule of glucose-6-P that is oxidatively decarboxylated to ribulose-5-P
- Produce ribose-5-P from glucose-6-P
What does NADPH function as?
A strong reductant (electron donor)
What is the [NAD+]/[NADH] in liver cells?
~1000
What is the [NADP+]/[NADPH] in liver cells?
0.01
What are the 2 phases of the PPP?
- Oxidative
- Non-oxidative
Flux through both phases of the PPP is regulated to meet what 3 metabolic states?
- If increased NADPH is required
- If nucleotide pools need to be replenished
- If ATP levels in the cell are low
What happens in the PPP if increased NADPH is required?
Fructose-6-P and glyceraldehyde-3-P are used to resynthesize glucose-6-P, thereby maintaining flux through the oxidative phase
What happens if nucleotide pools need to be replenished?
The bulk of ribulose-5-P is converted to ribose-5-P, stimulating nucleotide biosynthesis
What does the PPP accomplish for the cell? (i.e. what are its functions)
- Generate NADPH (needed in lots of pathways and to detox ROS)
- Produce ribose-5-P for nucleotide synthesis
- Regenerate glucose-6-P (to maintain NADPH production)
What is the over all net reaction of the PPP?
6 Glucose-6-P + 12 NADP+ + 6 H2O –>
4 Fructose-6-P + 2 Glyceraldehyde-3-P + 12 NADPH + 12 H+ + 6 CO2
What are the key enzymes in the PPP?
- G6PD
- Transketolase and transaldolase
What is G6PD?
The enzyme that catalyzes the initial step in the PPP, converts glucose-6-P to 6-phosphogluconolactone
- Commitment step
- Feedback inhibited by NADPH
What is transketolase?
The enzyme that catalyzes the transfer of 2-carbon units among sugars in the PPP
What is transaldolase?
The enzyme the catalyzes the transfer of 3-carbon units among sugars in the PPP
What do transketolase and transaldolase do together?
Catalyze the reversible carbon shuffle reactions of the non-oxidative phase
What are examples of the PPP in everyday biochemistry?
G6PD deficiency
- Most common enzyme deficiency in the world
- Affects >400 million people
- 90% decrease in enzyme activity results in inability of RBCs to make enough NADPH to protect the cells from ROS
- ROS generated by antimalarial drugs and compounds in fava beans
Which reaction(s) in the oxidative phase of the PPP is/are reversible?
- Lactonase
Which reaction(s) in the oxidative phase of the PPP is/are NOT reversible?
- G6PD
- 6PGD (6-Phosphogluconolactonate dehydrogenase)
Since glucose-6-P is a substrate for glycolysis and the PPP, what controls the overall metabolic flux through these pathways?
The [NADP+]/[NADPH] in the cytosol
- Acts as a rheostat to regulate G6PD activity
What is glutathione (GSH)?
Reduced form is an electron donor in redox reactions
What are the electrons from GSH used for?
- To keep cysteine residues in hemoglobin in a reduced state
- To reduce ROS and hydroxyl free radicals that damage proteins and lipids via oxidation-induced cleavage reactions
What is primaquine?
Antimalarial drug that causes oxidative stress in RBCs, which creates a hostile environment for the malaria parasite
- Leads to acute hemolytic anemia in people with a G6PD deficiency
What is gluconeogenesis?
Metabolic pathway used for the production of glucose from noncarbohydrate sources
How many enzymes do glycolysis and gluconeogenesis share?
7 enzymes
Which enzymes are glycolytic-specific?
- Hexokinase
- Phosphofructokinase-1
- Pyruvate kinase
What are the carbon sources for gluconeogenesis?
- Lactate
- Amino acids
- Glycerol
How do plants get carbon for gluconeogenesis?
Use the Calvin cycle to convert CO2 to glyceraldehyde-3-P
What does gluconeogenesis accomplish for the cell?
- Liver and kidneys use it to generate glucose from noncarbohydrate sources for export to other tissues that use glucose for energy
- Plants use it to convert CO2 to glyceraldehyde-3-P
What is the overall net reaction of gluconeogenesis?
2 Pyruvate + 2 NADH + 4 ATP + 2 GTP + 6 H2O –> 2 NAD+ + 2 H+ + 4 ADP + 2 GDP + 6 Pi
What are the key enzymes in gluconeogenesis?
- Pyruvate carboxylase
- Phosphoenolpyruvate carboxykinase
- FBPase-1
- Glucose-6-phosphotase
What is pyruvate carboxylase?
ATP-dependent enzyme that carboxylates pyruvate to generate oxaloacetate
- MITOCHONDRIAL ENZYME
What does pyruvate carboxylase maintain flux through?
Maintains flux through the citric acid cycle in the presence of acetyl-CoA
What is phosphoenolpyruvate carboxykinase?
Catalyzes a decarboxylation reaction in gluconeogenesis that converts oxaloacetate to phosphoenolpyruvate and CO2
What is FBPase-1?
Converts fructose-1,6-BP to fructose-6-P and opposes the PFK-1 in glycolysis
What is glucose-6-phosphotase?
Converts glucose-6-P to glucose and opposes the hexokinase/glucokinase reaction in glycolysis
What are examples of gluconeogenesis in everyday biochemistry?
Cori cycle
- Short intense exercise –> lactic acid build up in muscle because of anaerobic glycolysis
- Warm down period to increase circulation and remove lactate from muscle
- Lactate goes to liver where it’s converted to glucose and sent back to muscle to replenish glycogen
What are the 3 bypass reactions in gluconeogenesis?
- Pyruvate carboxylase and phosphoenolpyruvate carboxykinase (pyruvate kinase)
- FBPase-1 (PFK-1)
- Glucose-6-phosphotase (hexokinase)
What happens in the first bypass reaction in gluconeogenesis?
- Pyruvate carboxylase uses phosphoryl transfer energy in ATP to drive carboxylation reaction that converts pyruvate to oxaloacetate
- Oxaloacetate is decarboxylated by phosphoenolpyruvate carboxykinase and converted to phosphoenolpyruvate