Problem 9 A mutation in Phosphofructokinase causes the loss of the allosteric site for ATP. Which effect on glycolysis is expected? Explain in detail. Explain which of the following mutations would result in the opposite effect on the rate of glycolysis in liver: a) a mutation causing the loss of the binding site for citrate in phosphofructokinase b) a mutation causing the loss of the binding site for fructose 1,6-bisphosphate in pyruvate kinase. c) A mutation decreasing the activity of adenylate kinase

OneClass: Problem 9 A mutation in Phosphofructokinase causes the loss of the allosteric site for ATP....

Phosphofructokinase (PFK1) is a glycolytic enzyme that catalyzes the irreversible transfer of a phosphate from ATP to fructose -6-phosphate to form fructose-1, 6- bisphosphate.

fructose-6-phosphate + ATP --> fructose-1,6-bisphosphate + ADP

PFK1 is the key regulatory enzyme for glycolysis. When ATP levels are high in the cell, the cell no longer needs metabolic energy production to occur. In the case of these high energy levels, PFK1's activity is inhibited by allosteric regulation by ATP, which essentially closes the valve on the flow of carbohydrates through glycolysis.

Recall that allosteric regulators bind to a different site on the enzyme rather than the active (catalytic) site. ATP binds to the regulatory site and decreases PFK1 activity. ATP bound in the regulatory site acts as a modulator by lowering the affinity of PFK1 for its substrate, fructose-6-phosphate. AMP on the other hand, which is generated when the cell is in a low energy state binds to allosteric site and increases enzyme activity.

7. The enzyme PFK1 is an example of a non-regulatory enzyme or regulatory enzyme?

8. How is PFK regulated?

A. It is not regulated because it is a non-regulatory enzyme

B. allosteric enzyme regulation

C. covalent enzyme regulation

D. or proteolytic cleavage enzyme regulation?

9. What is the substrate and to which site on the enzyme does it bind? Which compounds are the positive and negative effectors?

10. In which conformational state would the enzyme be when negative inhibitors bind and in which conformational state would the enzyme be when positive inhibitors bind?

11. PFK1 is a heterotropic or homotropic regulatory enzyme?

12. Draw (or insert the picture from your course packet available on Canvas) the graph that corresponds to this reaction. Your graph should include the activity of PFK without bound effectors, with bound positive effector, and with bound negative effector. Label (or describe) each line to distinguish these along with which molecules are positive and negative effectors.

13. How does Vmax and K0.5 change with the positive and negative effectors?

i need question number nine please

Case Study Section 2 â glycolysis
Based on âMonday at the Metabolic Clinic, Adventures in Glycolysisâ by Nancy Boury (National Center for Case Study Teaching in Science)

Background:
You have been chosen for a very competitive undergraduate clinical internship at St. Visintainerâs Hospital and Metabolic Clinic working with Dr. Saccharo, an expert in enzyme deficiency disorders related to glycolysis. Before your first day Dr. Saccharo has asked that you review the reactions of glycolysis and the concept of isoenzymes.

Recall that isoenzymes are groups of enzymes that catalyze the same reaction in that they use the same reactants to product the same products. They may have different genes, tissue expression, developmental timing of expression, and affinities for their substrates. As an example, phosphofructokinase-1 has 3 isoenzyme forms: PFK-L is expressed in the liver and the gene is found on chromosome 21; PFK-M is expressed in the muscle and the gene is found on chromosome 12; and PFK-P is expressed in platelets and the gene is found on chromosome 10.

Question 1:
If a person would be deficient in all 3 forms of PFK-1, this person would .
A. Have lower than normal glycogen stores.
B. Have more mitochondrial activity than normal.
C. Be dead.
D. Produce more energy per glucose molecule because glycolysis would be unregulated.

It is now Monday morning and you are ready to start seeing patients with Dr. Saccharo.

Patient 1:
Ann is a teenager and avid golfer who was referred to the clinic after being refused at the blood drive and tiring easily on the high school golf course during practice. Ann is examined and a blood sample was obtained for analysis of a glycolysis related metabolic panel. The results of her panel is below (levels: + = normal, - = decreased; ++= increased):
Blood Metabolic Panel
Blood Glucose +
Glucose-6-phosphate ++
Fructose-6-phosphate ++
Fructose-1,6,bisphosphate ++
Glyceraldehyde-3-phosphate ++
1,3-bisphosphoglycerate ++
Phosphoenolpyruvate ++
Pyruvate -
ATP -
Red Blood Cell Concentration -
Question 2:
Assuming that Dr. Saccharo is correctly assuming that Ann has a defect in glycolysis, what glycolytic enzyme is the most likely to have the defect based on the blood metabolic profile?
A. Hexokinase
B. Phosphofructokinase
C. Triose Phosphate Isomerase
D. Pyruvate Kinase
E. Aldolase

Patient 2:
Marie is a 32-year-old mother of three complaining of fatigue and muscle cramps with exercise. She had always blamed her intolerance to exercise on her sedentary lifestyle. However, she recently joined a gym and after a week of aerobics classes went to her physician, who ordered a series of blood tests. The blood work came back with abnormal results, leading to her muscle biopsy and referral to the metabolic clinic. Marieâs blood was subjected to the same metabolic panel used before with the following results:
Blood Metabolic Panel
Blood Glucose +
Glucose-6-phosphate ++
Fructose-6-phosphate ++
Fructose-1,6,bisphosphate -
Glyceraldehyde-3-phosphate -
1,3-bisphosphoglycerate -
Pyruvate -
ATP -
Red Blood Cell Concentration -

Marieâs muscle biopsy was also analyzed and showed an excess of glycogen.

Question 3:
What is the most likely enzyme deficiency for Marie?
A. Hexokinase
B. Phosphofructokinase
C. Triose Phosphate Isomerase
D. Pyruvate Kinase
E. Aldolase

Question 4:
If you wanted to test the ability of red blood cells to complete glycolysis what compound would you try to detect?
A. Fructose-6-phosphate
B. Aldolase
C. Pyruvate
D. Phosphofructokinase
E. Dihydroxyacetone phosphate

Question 5:
If you used a sample of Marieâs blood for this, what compound could you add to enable these cells to complete glycolysis?
A. Glucose
B. Fructose-1,6-bisphosphate
C. Insulin
D. Glucagon
E. Fructose-6-phosphate

Patient 3:
Leo is a 25-year-old accountant that is not anemic, has perfect teeth, but has experienced two fainting spells recently. One happened after accidentally drinking a non-diet soda; the other after eating ânaturally sweetenedâ fruit salad. His dentist referred him to Dr. Saccharoâs clinic. Dr. Saccharo suspects Leo may have Hereditary Fructose Intolerance (HFI) and has recommended a closely monitored fructose tolerance test.

Hereditary Fructose Intolerance is a recessive disorder where individuals lack a functional copy of one isoform of the enzyme aldolase, specifically Aldolase B (also known as fructose-1-phosphate aldolase). In the liver, fructose is phosphorylated by Fructokinase to fructose-1-phosphate, then is cleaved by Aldolase B to glyceraldehyde and dihydroxyacetone phosphate. Fructose-1-phosphate is also a known allosteric inhibitor of Glycogen Phosphorylase, the primary enzyme responsible for releasing glucose from glycogen.

Question 6:
As compared to a normal individual that consumes fructose, a person with HFI who ingested fructose would have (select all that apply):
A. High levels of blood fructose
B. High levels of blood fructose-1-phosphate
C. High levels of blood glucose
D. Low levels of blood fructose
E. Low levels of blood glucose

That afternoon Leo undergoes the fructose tolerance test with the following results:

Question 7:
Based on the results of the test, what was the effect of giving Leo the intravenous fructose?
A. A rise in blood glucose levels
B. A decrease in blood glucose levels
C. An increase in glycogen stores
D. A rapid drop in blood pressure

However there were complications: Soon after the test Leo orders and drinks a cup of tea, but after half the cup Leo passes out. Dr. Saccharo orders two sequential blood glucose checks. The first was 50 mg/dl and 15 minutes later Leoâs blood glucose was down to 40 mg/dl. With those results Dr. Saccharo injected something into Leoâs IV and within minutes Leo was back to normal.

Question 8:
From these results does it appear that Leo has HFI?
A. Yes
B. No
C. It is unclear from the results

Question 9:
What did Dr. Saccharo inject into Leoâs IV line?
A. Insulin
B. Glucagon
C. Glucose
D. Fructose
E. Phosphofructokinase

Dr. Saccharo puts Leo on a restricted diet and orders follow-up visits.

Question 10:
Which of the following foods/ingredients would Leo NOT be allowed to eat?
A. Artificial sweeteners
B. High starch foods, such as potatoes
C. Sweet tea made with cane sugar
D. Any dairy products

Dr. Saccharo puts Leo on a restricted diet and orders follow-up visits.

Case Study Section 2 â glycolysis
Based on âMonday at the Metabolic Clinic, Adventures in Glycolysisâ by Nancy Boury (National Center for Case Study Teaching in Science)

Background:
You have been chosen for a very competitive undergraduate clinical internship at St. Visintainerâs Hospital and Metabolic Clinic working with Dr. Saccharo, an expert in enzyme deficiency disorders related to glycolysis. Before your first day Dr. Saccharo has asked that you review the reactions of glycolysis and the concept of isoenzymes.

Recall that isoenzymes are groups of enzymes that catalyze the same reaction in that they use the same reactants to product the same products. They may have different genes, tissue expression, developmental timing of expression, and affinities for their substrates. As an example, phosphofructokinase-1 has 3 isoenzyme forms: PFK-L is expressed in the liver and the gene is found on chromosome 21; PFK-M is expressed in the muscle and the gene is found on chromosome 12; and PFK-P is expressed in platelets and the gene is found on chromosome 10.

Question 9:
What did Dr. Saccharo inject into Leoâs IV line?
A. Insulin
B. Glucagon
C. Glucose
D. Fructose
E. Phosphofructokinase

indigolocust876

Case Study Section 2 â glycolysis
Based on âMonday at the Metabolic Clinic, Adventures in Glycolysisâ by Nancy Boury (National Center for Case Study Teaching in Science)

Background:
You have been chosen for a very competitive undergraduate clinical internship at St. Visintainerâs Hospital and Metabolic Clinic working with Dr. Saccharo, an expert in enzyme deficiency disorders related to glycolysis. Before your first day Dr. Saccharo has asked that you review the reactions of glycolysis and the concept of isoenzymes.

Recall that isoenzymes are groups of enzymes that catalyze the same reaction in that they use the same reactants to product the same products. They may have different genes, tissue expression, developmental timing of expression, and affinities for their substrates. As an example, phosphofructokinase-1 has 3 isoenzyme forms: PFK-L is expressed in the liver and the gene is found on chromosome 21; PFK-M is expressed in the muscle and the gene is found on chromosome 12; and PFK-P is expressed in platelets and the gene is found on chromosome 10.

Patient 1:
Ann is a teenager and avid golfer who was referred to the clinic after being refused at the blood drive and tiring easily on the high school golf course during practice. Ann is examined and a blood sample was obtained for analysis of a glycolysis related metabolic panel. The results of her panel is below (levels: + = normal, - = decreased; ++= increased):
Blood Metabolic Panel
Blood Glucose +
Glucose-6-phosphate ++
Fructose-6-phosphate ++
Fructose-1,6,bisphosphate ++
Glyceraldehyde-3-phosphate ++
1,3-bisphosphoglycerate ++
Phosphoenolpyruvate ++
Pyruvate -
ATP -
Red Blood Cell Concentration -

Question 2:
Assuming that Dr. Saccharo is correctly assuming that Ann has a defect in glycolysis, what glycolytic enzyme is the most likely to have the defect based on the blood metabolic profile?
A. Hexokinase
B. Phosphofructokinase
C. Triose Phosphate Isomerase
D. Pyruvate Kinase
E. Aldolase

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