Lecture 3: Carbohydrate Metabolism Flashcards
What does GLUT 1 transport? Does it have a low or high affinity?
RBC and Brain High Affinity (so low Km)
What does GLUT 2 transport? Does it have a low or high affinity?
Liver Low Affinity (so high Km)
What does GLUT 3 transport? Does it have a low or high affinity?
Neurons High Affinity (so low Km)
What does GLUT 4 transport? What is it dependent on?
Skeletal Muscle, Heart, Adipose Tissue
Insulin dependent
When insulin signals a cell that utilizes GLUT 4, what happens?
GLUT 4 transporter sequestered in cell will insert itself into plasma membrane to induce glucose uptake
Where does glycolysis occur?
Cytoplasm
What is the net yield of glycolysis with one glucose molecule?
2 ATP
2 NADH
2 pyruvate
What is the difference between hexokinase and glucokinase?
What do these enzymes do?
Hexokinase: utilized in all cells
-High affinity (low Km)
Glucokinase: pancreas and liver only
- Low affinity (high Km)
- Most active with high glucose levels
Both convert glucose to glucose 6-P
What activates and inhibits step 1 of glycolysis?
Activators:
Glucose
Insulin
Fructose 1-P
Inhibitors
Glucose 6-P/Fructose 6-P
Glucagon
What is the rate limiting step of glycolysis? What enzyme is involved?
Step 3: Fructose 6-P –> Fructose 1,6-BP
via PFK-1 (phosphofructokinase-1)
What activates and inhibits rate limiting step of glycolysis?
Activators:
Fructose 2,6-P
AMP
Inhibitors:
Citrate
ATP
Which step yields NADH?
Step 6: G3P –> 1,3 BPG
via Glyceraldehyde 3P dehydrogenase (GADPH)
When 1,3BPG –> 3-PG, what enzyme is used and what is a product of this reaction?
Phosphoglycerate kinase
ATP
How is pyruvate formed?
PEP –> Pyruvate via pyruvate kinase
ATP is produced
How does glucokinase allow glucose to enter liver and pancreatic cells?
When there is high glucose, Fructose 6-P will promote the translocation of nucleus.
Most of the time, glucokinase is sequestered by GK-Regulatory Protein. Glucokinase moves to cytoplams.
Insulin induces synthesis.
How does PFK-2 regulate glycolysis?
Fructose 6-P produces Fructose 2,6-BP via PFK 2.
PFK 2 promotes PFK 1 (hence promoting glycolysis)
When PFK is dephosphorylated, it is favored by insulin.
When PFK is phosphorylated, it is favored by glucagon.
What happens to glycolysis when insulin levels are high and glucagon levels are low? (fed state)
Insulin promotes dephosphorylation of PFK 2.
Fru 2,6 BP is produced –> promote PFK 1
What happens to glycolysis when glucagon levels are high and insulin levels are low? (fasting state)
Glucagon induces Protein Kinase A, which phosphorylates PFK-2, reducing PFK-1 activity.
What is Tarui Disease?
Deficiency of PFK-1
-Can cause muscle weakness
How is pyruvate kinase regulated?
Activators:
Insulin: dephosphorylates PK
Fructose 1,6-BP
Inhibitors:
Glucagon: phosphorylates PK
Alanine
ATP
What pathways can intermediate Glucose 6-P be utilized in?
Glucose 6-P:
-Pentose Phosphate Pathway (precursor)
As Glucose 1-P:
- Galactose metabolism
- Glycogen Synthesis
- Uronic Acid Pathway
What are the fates of pyruvate?
Acetyl Co A –> TCA Cycle
Alanine –> Protein synthesis, gluconeogenesis, urea cycle
Oxaloacetate –> Gluconeogensis
Lactate –> Cori Cycle
What cells are most affected by glycolysis disorders? What is the biggest clinical finding?
Red Blood Cells (no mitochondria)
-hemolytic anemia
When the brain can no longer utilize glucose as a fuel source, what will it use?
Ketone Bodies
What are clinical markers for hemolytic anemia?
Elevated Lactate Dehydrogenase
Unconjugated bilirubin