Glycolysis Flashcards
Glycolysis can be either aerobic or anaerobic. What is the main difference in their products?
Both types of glycolysis the product is pyruvate. Anaerobic glycolysis takes it a step further and converts pyruvate to lactate
Location of glycolysis?
Aerobic glycolysis can happen in cells that have ___
Cytoplasm
Mitochondria (paths that happen in mitochondria are the ones that make the most ATP)
Anaerobic glycolysis would happen in tissues where __
Name 4 places in the body that relies on anaerobic glycolysis
Blood supply is very minimal or there is no oxygen
Medulla of kidney, RBCs, contracting skeletal muscle and cornea/lens of eyes (if these were vascularized, you would lose vision)
First 5 steps in glycolysis vs the steps afterwards?
First 5 steps = investing phase (energy is utilized), steps after you start getting a profit (energy production)
Glycolysis overview:
The first 5 steps of glycolysis are acting to do what?
Splitting one glucose molecule into 2 glyceraldehyde-3-phosphates
ATP is generated in what two steps?
Which of these is reversible?
ATP is generated in steps 7 and 10
7 is reversible, 10 is not
Each product that is generated in steps 6-10 are from?
Each of the glyceraldehyde-3-phosphates generated in steps 4 and 5. (So thats why everything is doubled, because there are 2 glyceraldehyde-3-phosphates)
NADH is generated in which step?
Why is NADH important?
6
Its an electron carrier with the potential to make more ATPs through oxidative phosphorylation
Which steps require ATP
Steps 1 and 3
First step:
- Glucose is converted to ____ by ___?
- When this step starts, why does the product get trapped in the cell?
- What has to happen to become not stuck?
- Glucose-6-phosphate by hexokinase/glucokinase
- Cells lack transport systems for phosphorylated glucose (GLUT transporters only work on glucose)
- Glucose-6-phosphate has to be oxidized
Functions of hexokinase and glucokinase
Phosphorylates glucose, and uptake of glucose by the tissue (GLUT)
Hexokinase:
- Provides energy when glucose concentration is high or low?
- __ Km; __ Vmax
- Inhibited by?
- Low (fasting state)
- Low Km (high affinity for glucose); low Vmax
- Glucose-6-phosphate
Glucokinase:
- Location
- __ Km; __ Vmax
- Induced by?
- Provides energy when glucose concentration is high or low?
- Liver and islet cells of pancreas
- High Km; high Vmax
- Insulin
- High
Key feature about glucokinase?
~what GLUT transporter transports to liver and pancreas?
Acts as a glucose sensor to let pancreas know that insulin needs to be released
~GLUT2
Broad path of how glucokinase works
Carb rich meal increased blood glucose, GLUT2 transports to pancreas and increases glucose concentration of beta cells, glucose gets phosphorylated to enter glycolysis and TCA. ATP builds up and is stored in channels by the beta cells
- What are the two channels where ATP is stored?
- The amount of glucose entering beta cell is equal to?
- Relationship between potassium channels and insulin?
- Potassium channel and voltage dependent calcium channel
- Amount of insulin being secreted from beta cells into the blood
- If K channels close, you cannot secrete insulin
Step 3: irreversible
- ____ is converted to ____ by ?
- What is significant about this step
- What is significant about PFK1?
- Fructose-6-phosphate to fructose 1,6 bisphosphate by PFK1
- This is the rate limiting step (committed step)
- It is the most regulated enzyme
Function of Aldolase A and B
Aldolase A= cleaves fructose 1,6 bisphosphate to 2 triose sugars
Aldolase B= cleaves fructose-6-phosphate and is part of fructose metabolism (so not involved in glycolysis)
What are incretins
Peptides in GI that are secreted when we eat. They act on beta cells and increase insulin secretion (thats how positively charged amino acids can increase insulin secretion; increase positive charge leads to depolarization)
What is needed in order to get insulin out of its storage vesicle?
Calcium
Function of glyceraldehyde 3 phosphate dehydrogenase? (G3P dehydrogenase)
What does this step require?
Catalyzes the only step where NADH is synthesized (step 6)
Requires inorganic phosphate (Pi) to attach to carboxyl group
Clinical relevance of arsenic poisioning?
It competes with G3P dehydrogenase, thereby preventing net NADH and ATP production (takes all the energy out of glycolysis)
- What increases O2 delivery (ie at high altitudes)?
- How does it do this?
- What is the function of 1,3-biphosphoglycerate
- 2,3-biphosphoglycerate
- Favors unloading of O2 to tissues, High BPG shifts oxygen dissociation curve to the right
- Intermediate of RBC responsible for accepting or releasing oxygen in the tissues
- What enzyme is inhibited by fluoride?
2. Explain
- Enolase
- Bacteria can form lactic acid from food which turns teeth yellow. Fluoride prevents glycolysis that forms the lactic acid
- What catalyzes the second substrate level phosphorylation step in glucose?
- What happens?
- Pyruvate kinase
- Enzyme mediates the transfer of phophates from PEP to ADP forming two ATPs; PEP is converted to pyruvate (end product of aerobic glycolysis)
Metabolic fate of pyruvate:
- Aerobic conditions?
- Anaerobic?
- Can be converted to acetyl CoA and enter Krebs cycle; acetyl CoA is completely oxidized and generates ATP through oxidative phosphorylation in Krebs
- Seen mainly in RBCs and contracting skeletal muscle; pyruvate is converted to lactate
Ratio of NADH to NAD is high, what will happen to lactate?
It will increase
So the enzymes that catalyze the irreversible and regulated steps of glycolysis are?
Hexokinase, glucokinase, PFK1, and pyruvate kinase
What does PFK2 do?
Controls PFK1 of glycolysis in the liver - covalent modification
Clinical correlations for glucokinase:
- It is induced by?
- Type 1 diabetes?
- Hyperinsulinemia and hypoglycemia?
- Gestational diabetes (MODY)?
- Insulin (so if you dont have insulin, you cannot make glucokinase)
- If you have a near complete deficiency in glucokinase
- Decrease Km
- Increase Km (decreased activity of glucokinase)
PFK1 is only activated if __ is present
Positive allosteric effector?
Negative allosteric effector?
Fructose 2,6 bisphosphate (even if citrate levels are high)
High fructose 2,6 bisphosphate (liver), high ADP (liver) / High AMP (muscle)
Citrate (liver)
Two inhibitors of PFK1 and why one of them is significant?
Citrate and ATP; citrate is the only example of a CAC intermediate regulating a glycolytic enzyme
High glucagon (cAMP) inactivates?
Effect of this?
PFK2 (because high glucagon means fructose 2,6 bisphosphate decreases in liver cells)
Effect is glycolysis will decrease and gluconeogenesis will increase
- Hormonal control of glycolysis in well fed state
2. Fasting state
- Uptake of glucose by GLUT4 (skeletal muscle and adipose), utilization of glucose by oxidation, anabolic pathways
- Decrease in utilization of glucose by oxidation by inactivation of the key glycolytic enzymes
- Pyruvate kinase deficiency will lead to decrease in rate of?
- What does this mainly affect in the body?
- Associated with a rise in?
- Clinical presentation?
- Glycolysis
- RBCs that depend solely on anaerobic glycolysis
- 2,3 BPG levels
- Hemolytic anemia (due to lysis of RBCs)
- What is lactic acidosis?
- What is it the result of?
- May be seen associated with?
- Accumulation of lactic acid in blood
- Failure of delivery of oxygen to tissues - dependent on anaerobic glycolysis
- Severe MI, uncontrolled hemorrhage
What is a fluoride bulb?
Used for blood glucose estimation since fluoride blocks glycolysis, adding it to the blood inhibits glucose utilization in vitro - prevents false low values for blood glucose
**Starting with glyceraldehyde-3-PO4 and synthesizing one molecule of pyruvate, the net yield of ATP and NADH would be?
2 ATP and 1 NADH
If someone who does not exercise often is hiking 2500 meters above sea level, how many ATPs would be generated by his/her RBCs?
Zero
Why is it bad to drink alcohol after running a marathon?
Running a marathon produces a lot of lactic acid and you will be dehydrated - this will result in lactic acidosis
